Non-linear frequency-dependence of neurovascular coupling in the cerebellar cortex implies vasodilation-vasoconstriction competition

Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood-oxygen-level-dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere. The capillary diameter increased in response to mossy fiber activation in the 6-300Hz range, with a marked inflection around 50Hz (vermis) and 100Hz (hemisphere). The corresponding NA was recorded using high-density multi-electrode arrays and correlated to capillary dynamics through a computational model dissecting the main components of granular layer activity. Here, NVC is known to involve a balance between the NMDAR-NO pathway driving vasodilation and the mGluRs-20HETE pathway driving vasoconstriction. Simulations showed that the NMDAR-mediated component of NA was sufficient to explain the time-course of the capillary dilation but not its non-linear frequency-dependence, suggesting that the mGluRs-20HETE pathway plays a role at intermediate frequencies. These parallel control pathways imply a vasodilation-vasoconstriction competition hypothesis that could adapt local hemodynamics at the microscale bearing implications for fMRI signals interpretation.

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Two distinct profiles of fMRI and neurophysiological activity elicited by acetylcholine in visual cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1808507115 ◽

2018 ◽

Vol 115 (51) ◽

pp. E12073-E12082 ◽

Cited By ~ 6

Author(s):

Daniel Zaldivar ◽

Alexander Rauch ◽

Nikos K. Logothetis ◽

Jozien Goense

Keyword(s):

Visual Cortex ◽

Injection Site ◽

Blood Oxygen Level Dependent ◽

Local Injection ◽

Electrode Arrays ◽

Blood Oxygen Level ◽

Neural Signals ◽

Electrophysiological Recordings ◽

High Gamma ◽

Neurophysiological Activity

Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays. We found that local injection of ACh elicited two distinct profiles of fMRI and neurophysiological activity, depending on the distance from the injector. Near the injection site, we observed an increase in the baseline blood oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) responses, while their visual modulation decreased. In contrast, further from the injection site, we observed an increase in the visually induced BOLD and CBF modulation without changes in baseline. Neurophysiological recordings suggest that the spatial correspondence between fMRI responses and neural activity does not change in the gamma, high-gamma, and multiunit activity (MUA) bands. The results near the injection site suggest increased inhibitory drive and decreased metabolism, contrasting to the far region. These changes are thought to reflect the kinetics of ACh and its metabolism to choline.

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Cortical Depth-Dependent Temporal Dynamics of the BOLD Response in the Human Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.57 ◽

2011 ◽

Vol 31 (10) ◽

pp. 1999-2008 ◽

Cited By ~ 80

Author(s):

Jeroen CW Siero ◽

Natalia Petridou ◽

Hans Hoogduin ◽

Peter R Luijten ◽

Nick F Ramsey

Keyword(s):

Human Brain ◽

Gray Matter ◽

Animal Studies ◽

Temporal Dynamics ◽

Onset Time ◽

Neurovascular Coupling ◽

Blood Oxygen Level Dependent ◽

Peak Time ◽

Blood Oxygen Level ◽

Coupling Mechanisms

Recent animal studies at high field have shown that blood oxygen level-dependent (BOLD) contrast can be specific to the laminar vascular architecture of the cortex, by differences in its temporal dynamics in reference to cortical depth. In this study, we characterize the temporal dynamics of the hemodynamic response (HDR) across cortical depth in the human primary motor and visual cortex, at 7T and using very short stimuli and with high spatial and temporal resolution. We find that the shape and temporal dynamics of the HDR changed in an orderly manner across cortical depth. Compared with the pial vasculature, HDRs in deeper gray matter are significantly faster in onset time (by ∼ 0.5 second) and peak time (∼2 seconds), and are narrower (by ∼1 second) and with smaller amplitude, in line with the known vascular organization across cortical depth and the transit of deoxygenated blood through the vasculature. The width of the HDR in deeper gray matter was as short as 2.1 seconds, indicating that neurovascular coupling takes place at a shorter timescale than previously reported in the human brain. These findings open the possibility to probe layer-specific hemodynamics and neurovascular coupling mechanisms in human gray matter.

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Neurovascular Coupling in Development and Disease: Focus on Astrocytes

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.702832 ◽

2021 ◽

Vol 9 ◽

Author(s):

Teresa L. Stackhouse ◽

Anusha Mishra

Keyword(s):

Blood Flow ◽

Energy Demand ◽

Neurovascular Unit ◽

Neurovascular Coupling ◽

Time Frame ◽

Blood Oxygen Level Dependent ◽

High Energy ◽

Neural Activation ◽

Blood Oxygen Level ◽

Similar Time

Neurovascular coupling is a crucial mechanism that matches the high energy demand of the brain with a supply of energy substrates from the blood. Signaling within the neurovascular unit is responsible for activity-dependent changes in cerebral blood flow. The strength and reliability of neurovascular coupling form the basis of non-invasive human neuroimaging techniques, including blood oxygen level dependent (BOLD) functional magnetic resonance imaging. Interestingly, BOLD signals are negative in infants, indicating a mismatch between metabolism and blood flow upon neural activation; this response is the opposite of that observed in healthy adults where activity evokes a large oversupply of blood flow. Negative neurovascular coupling has also been observed in rodents at early postnatal stages, further implying that this is a process that matures during development. This rationale is consistent with the morphological maturation of the neurovascular unit, which occurs over a similar time frame. While neurons differentiate before birth, astrocytes differentiate postnatally in rodents and the maturation of their complex morphology during the first few weeks of life links them with synapses and the vasculature. The vascular network is also incomplete in neonates and matures in parallel with astrocytes. Here, we review the timeline of the structural maturation of the neurovascular unit with special emphasis on astrocytes and the vascular tree and what it implies for functional maturation of neurovascular coupling. We also discuss similarities between immature astrocytes during development and reactive astrocytes in disease, which are relevant to neurovascular coupling. Finally, we close by pointing out current gaps in knowledge that must be addressed to fully elucidate the mechanisms underlying neurovascular coupling maturation, with the expectation that this may also clarify astrocyte-dependent mechanisms of cerebrovascular impairment in neurodegenerative conditions in which reduced or negative neurovascular coupling is noted, such as stroke and Alzheimer’s disease.

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Cross‐hole radar attenuation tomography using a frequency centroid down‐shift method: Consideration of non‐linear frequency dependence of EM wave attenuation

10.1190/1.1885928 ◽

1997 ◽

Cited By ~ 1

Author(s):

Lanbo Liu ◽

Chaoguang Zhou ◽

John W. Lane ◽

F. Peter Haeni

Keyword(s):

Frequency Dependence ◽

Wave Attenuation ◽

Shift Method ◽

Linear Frequency ◽

Non Linear

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Functional White-Laser Imaging to Study Brain Oxygen Uncoupling/Recoupling in Songbirds

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.189 ◽

2010 ◽

Vol 31 (2) ◽

pp. 393-400 ◽

Cited By ~ 12

Author(s):

Stéphane Mottin ◽

Bruno Montcel ◽

Hugues Guillet de Chatellus ◽

Stéphane Ramstein

Keyword(s):

Time Course ◽

Brain Aging ◽

Optical Tomography ◽

Blood Oxygen Level Dependent ◽

Blood Oxygen ◽

Blood Oxygen Level ◽

Subsequent Increase ◽

Brain Oxygen ◽

Concentration Changes

Contrary to the intense debate about brain oxygen dynamics and its uncoupling in mammals, very little is known in birds. In zebra finches, picosecond optical tomography with a white laser and a streak camera can measure in vivo oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) concentration changes following physiologic stimulation (familiar calls and songs). Picosecond optical tomography showed sufficient submicromolar sensitivity to resolve the fast changes in the hippocampus and auditory forebrain areas with 250 μm resolution. The time course is composed of (1) an early 2-second-long event with a significant decrease in Hb and HbO2 levels of −0.7 and −0.9 μmol/L, respectively, (2) a subsequent increase in blood oxygen availability with a plateau of HbO2 (+ 0.3 μmol/L), and (3) pronounced vasodilatation events immediately after the end of the stimulus. One of the findings of our study is the direct link between blood oxygen level-dependent signals previously published in birds and our results. Furthermore, the early vasoconstriction event and poststimulus ringing seem to be more pronounced in birds than in mammals. These results in birds, tachymetabolic vertebrates with a long lifespan, can potentially yield new insights, e.g., into brain aging.

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Discrimination of Large Venous Vessels in Time-Course Spiral Blood-Oxygen-Level-Dependent Magnetic-Resonance Functional Neuroimaging

Magnetic Resonance in Medicine ◽

10.1002/mrm.1910330602 ◽

1995 ◽

Vol 33 (6) ◽

pp. 745-754 ◽

Cited By ~ 252

Author(s):

Adrian T. Lee ◽

Gary H. Glover ◽

Craig H. Meyer

Keyword(s):

Magnetic Resonance ◽

Time Course ◽

Functional Neuroimaging ◽

Blood Oxygen Level Dependent ◽

Blood Oxygen ◽

Oxygen Level ◽

Blood Oxygen Level

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Mesoscopic Mapping of Ictal Neurovascular Coupling in Awake Behaving Mice Using Optical Spectroscopy and Genetically Encoded Calcium Indicators

Frontiers in Neuroscience ◽

10.3389/fnins.2021.704834 ◽

2021 ◽

Vol 15 ◽

Author(s):

Fan Yang ◽

Jing Li ◽

Yan Song ◽

Mingrui Zhao ◽

James E. Niemeyer ◽

...

Keyword(s):

Cerebral Blood Volume ◽

Imaging Techniques ◽

Neurovascular Coupling ◽

Blood Oxygen Level Dependent ◽

Epileptic Focus ◽

Wide Field ◽

Blood Oxygen Level ◽

Optical Signals ◽

Hemoglobin Oxygenation ◽

Mapping Techniques

Unambiguously identifying an epileptic focus with high spatial resolution is a challenge, especially when no anatomic abnormality can be detected. Neurovascular coupling (NVC)-based brain mapping techniques are often applied in the clinic despite a poor understanding of ictal NVC mechanisms, derived primarily from recordings in anesthetized animals with limited spatial sampling of the ictal core. In this study, we used simultaneous wide-field mesoscopic imaging of GCamp6f and intrinsic optical signals (IOS) to record the neuronal and hemodynamic changes during acute ictal events in awake, behaving mice. Similar signals in isoflurane-anesthetized mice were compared to highlight the unique characteristics of the awake condition. In awake animals, seizures were more focal at the onset but more likely to propagate to the contralateral hemisphere. The HbT signal, derived from an increase in cerebral blood volume (CBV), was more intense in awake mice. As a result, the “epileptic dip” in hemoglobin oxygenation became inconsistent and unreliable as a mapping signal. Our data indicate that CBV-based imaging techniques should be more accurate than blood oxygen level dependent (BOLD)-based imaging techniques for seizure mapping in awake behaving animals.

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Disturbed neurovascular coupling in hemodialysis patients

PeerJ ◽

10.7717/peerj.8989 ◽

2020 ◽

Vol 8 ◽

pp. e8989 ◽

Cited By ~ 2

Author(s):

Mei Jin ◽

Liyan Wang ◽

Hao Wang ◽

Xue Han ◽

Zongli Diao ◽

...

Keyword(s):

Cognitive Processing ◽

Emotional Regulation ◽

Low Frequency ◽

Neurovascular Coupling ◽

Neural Mechanism ◽

Blood Oxygen Level Dependent ◽

Hemodialysis Patients ◽

Anterior Cingulate ◽

Healthy Controls ◽

Blood Oxygen Level

Background Altered cerebral blood flow (CBF) and amplitude of low-frequency fluctuation (ALFF) have been reported in hemodialysis patients. However, neurovascular coupling impairments, which provide a novel insight into the human brain, have not been reported in hemodialysis patients. Methods We combined arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) techniques to investigate neurovascular coupling alterations and its relationships with demographic and clinical data in 46 hemodialysis patients and 47 healthy controls. To explore regional neuronal activity, ALFF was obtained from resting-state functional MRI. To measure cerebral vascular response, CBF was calculated from ASL. The across-voxel CBF–ALFF correlations for global neurovascular coupling and CBF/ALFF ratio for regional neurovascular coupling were compared between hemodialysis patients and healthy controls. Two-sample t-tests were used to compare the intergroup differences in CBF and ALFF. Multiple comparisons were corrected using a voxel-wise false discovery rate (FDR) method (P < 0.05). Results All hemodialysis patients and healthy controls showed significant across-voxel correlations between CBF and ALFF. Hemodialysis patients showed a significantly reduced global CBF–ALFF coupling (P = 0.0011) compared to healthy controls at the voxel-level. Of note, decreased CBF/ALFF ratio was exclusively located in the bilateral amygdala involved in emotional regulation and cognitive processing in hemodialysis patients. In hemodialysis patients, the decreased CBF (right olfactory cortex, anterior cingulate gyrus and bilateral insula) and ALFF (bilateral precuneus and superior frontal gyrus) were mainly located in the default mode network and salience network-related regions as well as increased CBF in the bilateral thalamus. Conclusions These novel findings reveal that disrupted neurovascular coupling may be a potential neural mechanism in hemodialysis patients.

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