scholarly journals Pathway-Specific Variations in Neurovascular and Neurometabolic Coupling in Rat Primary Somatosensory Cortex

2009 ◽  
Vol 29 (5) ◽  
pp. 976-986 ◽  
Author(s):  
Pia Enager ◽  
Henning Piilgaard ◽  
Nikolas Offenhauser ◽  
Ara Kocharyan ◽  
Priscilla Fernandes ◽  
...  

Functional neuroimaging signals are generated, in part, by increases in cerebral blood flow (CBF) evoked by mediators, such as nitric oxide and arachidonic acid derivatives that are released in response to increased neurotransmission. However, it is unknown whether the vascular and metabolic responses within a given brain area differ when local neuronal activity is evoked by an activity in the distinct neuronal networks. In this study we assessed, for the first time, the differences in neuronal responses and changes in CBF and oxygen consumption that are evoked after the activation of two different inputs to a single cortical area. We show that, for a given level of glutamatergic synaptic activity, corticocortical and thalamocortical inputs evoked activity in pyramidal cells and different classes of interneurons, and produced different changes in oxygen consumption and CBF. Furthermore, increases in stimulation intensities either turned off or activated additional classes of inhibitory interneurons immunoreactive for different vasoactive molecules, which may contribute to increases in CBF. Our data imply that for a given cortical area, the amplitude of vascular signals will depend critically on the type of input, and that a positive blood oxygen level-dependent (BOLD) signal may be a consequence of the activation of both pyramidal cells and inhibitory interneurons.

2020 ◽  
Vol 376 (1815) ◽  
pp. 20190632
Author(s):  
Bradley C. Love

Notions of mechanism, emergence, reduction and explanation are all tied to levels of analysis. I cover the relationship between lower and higher levels, suggest a level of mechanism approach for neuroscience in which the components of a mechanism can themselves be further decomposed and argue that scientists' goals are best realized by focusing on pragmatic concerns rather than on metaphysical claims about what is ‘real'. Inexplicably, neuroscientists are enchanted by both reduction and emergence. A fascination with reduction is misplaced given that theory is neither sufficiently developed nor formal to allow it, whereas metaphysical claims of emergence bring physicalism into question. Moreover, neuroscience's existence as a discipline is owed to higher-level concepts that prove useful in practice. Claims of biological plausibility are shown to be incoherent from a level of mechanism view and more generally are vacuous. Instead, the relevant findings to address should be specified so that model selection procedures can adjudicate between competing accounts. Model selection can help reduce theoretical confusions and direct empirical investigations. Although measures themselves, such as behaviour, blood-oxygen-level-dependent (BOLD) and single-unit recordings, are not levels of analysis, like levels, no measure is fundamental and understanding how measures relate can hasten scientific progress. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.


Author(s):  
Emmanuel A. Stamatakis ◽  
Eleni Orfanidou ◽  
Andrew C. Papanicolaou

Functional magnetic resonance imaging (fMRI) is the most frequently used functional neuroimaging method and the one that accounts for most of the neuroimaging literature. It measures the blood oxygen level-dependent (BOLD) signal in different parts of the brain during rest and during task-induced activation of functional networks mediating basic and higher functions. A basic understanding of the various instruments and techniques of recording the hemodynamic responses of different brain regions and the manner in which we establish activation and connectivity patterns out of these responses is necessary for an appreciation of the contemporary functional neuroimaging literature. To facilitate such an understanding is the purpose of this chapter.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nikoloz Sirmpilatze ◽  
Jürgen Baudewig ◽  
Susann Boretius

Abstract Medetomidine has become a popular choice for anesthetizing rats during long-lasting sessions of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). Despite this, it has not yet been thoroughly established how commonly reported fMRI readouts evolve over several hours of medetomidine anesthesia and how they are affected by the precise timing, dose, and route of administration. We used four different protocols of medetomidine administration to anesthetize rats for up to six hours and repeatedly evaluated somatosensory stimulus-evoked BOLD responses and resting state functional connectivity. We found that the temporal evolution of fMRI readouts strongly depended on the method of administration. Intravenous administration of a medetomidine bolus (0.05 mg/kg), combined with a subsequent continuous infusion (0.1 mg/kg/h), led to temporally stable measures of stimulus-evoked activity and functional connectivity throughout the anesthesia. Deviating from the above protocol—by omitting the bolus, lowering the medetomidine dose, or using the subcutaneous route—compromised the stability of these measures in the initial two-hour period. We conclude that both an appropriate protocol of medetomidine administration and a suitable timing of fMRI experiments are crucial for obtaining consistent results. These factors should be considered for the design and interpretation of future rat fMRI studies.


2021 ◽  
Vol 22 (7) ◽  
pp. 3630
Author(s):  
Nayoung Kim ◽  
M. Justin Kim

Generalized anxiety disorder (GAD) is marked by uncontrollable, persistent worry and exaggerated response to uncertainty. Here, we review and summarize the findings from the GAD literature that employs functional neuroimaging methods. In particular, the present review focuses on task-based blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We find that select brain regions often regarded as a part of a corticolimbic circuit (e.g., amygdala, anterior cingulate cortex, prefrontal cortex) are consistently targeted for a priori hypothesis-driven analyses, which, in turn, shows varying degrees of abnormal BOLD responsivity in GAD. Data-driven whole-brain analyses show the insula and the hippocampus, among other regions, to be affected by GAD, depending on the task used in each individual study. Overall, while the heterogeneity of the tasks and sample size limits the generalizability of the findings thus far, some promising convergence can be observed in the form of the altered BOLD responsivity of the corticolimbic circuitry in GAD.


2021 ◽  
Author(s):  
Philipp Mächler ◽  
Natalie Fomin-Thunemann ◽  
Martin Thunemann ◽  
Marte Julie Sætra ◽  
Michèle Desjardins ◽  
...  

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase – the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O 2 (pO 2 ) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O 2 (CMRO 2 ) based on 2-photon pO 2 measurements around diving arterioles and applied this method to estimate baseline CMRO 2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO 2 from layer I to layer IV . This decrease of CMRO 2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O 2 reserve during surges of neuronal activity or certain metabolically active brain states rather than baseline energy needs. Our study provides the first quantification of microscopically resolved CMRO 2 across cortical layers as a step towards informed interpretation and modeling of cortical-layer-specific Blood Oxygen Level Dependent (BOLD) fMRI signals.


2019 ◽  
Author(s):  
Søren Grubb ◽  
Changsi Cai ◽  
Bjørn O. Hald ◽  
Lila Khennouf ◽  
Jonas Fordsmann ◽  
...  

AbstractActive nerve cells produce and release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling, which is the basis of the BOLD (blood-oxygen-level-dependent) functional neuroimaging signals. We here reveal a unique mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and the first capillary that links blood flow in capillaries to the arteriolar inflow. Large NG2-positive cells, containing smooth muscle actin, encircle the sphincters and rises in nerve cell activity cause astrocyte and neuronal Ca2+ rises that correlate to dilation and shortening of the sphincter concomitant with substantial increases in the RBC flux. Global ischemia and cortical spreading depolarization constrict sphincters and cause vascular trapping of blood cells. These results reveal precapillary sphincters as bottlenecks for brain capillary blood flow.


2019 ◽  
Author(s):  
Nikoloz Sirmpilatze ◽  
Jürgen Baudewig ◽  
Susann Boretius

Medetomidine has become a popular choice for anesthetizing rats during long-lasting sessions of blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). Despite this, it has not yet been established how commonly reported fMRI readouts evolve over several hours of medetomidine anesthesia and how they are affected by the precise timing, dose, and route of administration. We used four different protocols of medetomidine administration to anesthetize rats for up to six hours and repeatedly evaluated somatosensory stimulus-evoked BOLD responses and resting state functional connectivity throughout. We found that the temporal evolution of fMRI readouts strongly depended on the method of administration. Protocols that combined an initial medetomidine bolus (0.05 mg/kg) together with a subsequent continuous infusion (0.1 mg/kg/h) led to temporally stable measures of stimulus-evoked activity and functional connectivity. However, when the bolus was omitted, or the dose of medetomidine lowered, the measures attenuated in a time-dependent manner. We conclude that medetomidine can sustain consistent fMRI readouts for up to six hours of anesthesia, but only with an appropriate administration protocol. This factor should be considered for the design and interpretation of future preclinical fMRI studies in rats.


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