The cholinergic system modulates negative BOLD responses in the prefrontal cortex once electrical perforant pathway stimulation triggers neuronal afterdischarges in the hippocampus

Repeated high-frequency pulse-burst stimulations of the rat perforant pathway elicited positive BOLD responses in the right hippocampus, septum and prefrontal cortex. However, when the first stimulation period also triggered neuronal afterdischarges in the hippocampus, then a delayed negative BOLD response in the prefrontal cortex was generated. While neuronal activity and cerebral blood volume (CBV) increased in the hippocampus during the period of hippocampal neuronal afterdischarges (h-nAD), CBV decreased in the prefrontal cortex, although neuronal activity did not decrease. Only after termination of h-nAD did CBV in the prefrontal cortex increase again. Thus, h-nAD triggered neuronal activity in the prefrontal cortex that counteracted the usual neuronal activity-related functional hyperemia. This process was significantly enhanced by pilocarpine, a mACh receptor agonist, and completely blocked when pilocarpine was co-administered with scopolamine, a mACh receptor antagonist. Scopolamine did not prevent the formation of the negative BOLD response, thus mACh receptors modulate the strength of the negative BOLD response.

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From unspecific to adjusted, how the BOLD response in the rat hippocampus develops during consecutive stimulations

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16634715 ◽

2016 ◽

Vol 37 (2) ◽

pp. 590-604 ◽

Cited By ~ 7

Author(s):

Stephanie Riemann ◽

Cornelia Helbing ◽

Frank Angenstein

Keyword(s):

High Frequency ◽

Pulse Sequences ◽

Low Frequency ◽

Bold Response ◽

Deconvolution Analysis ◽

Bold Responses ◽

Electrical Pulses ◽

Stimulation Period ◽

Frequency Pulse ◽

Spiking Activity

To determine the possibility to deconvolve measured BOLD responses to neuronal signals, the rat perforant pathway was electrically stimulated with 10 related stimulation protocols. All stimulation protocols were composed of low-frequency pulse sequences with superimposed high-frequency pulse bursts. Because high-frequency pulse bursts trigger only one synchronized spiking of granular cells, variations of the stimulation protocol were used: (a) to keep the spiking activity similar during the presentation of different numbers of pulses, (b) to apply identical numbers of pulses to induce different amounts of spiking activity, and (c) to concurrently vary the number of applied electrical pulses and resultant spiking activity. When complex pulse sequences enter the hippocampus, an unspecific default-like BOLD response is first generated, which relates neither to the number of incoming pulses nor to the induced spiking activity. Only during subsequent stimulations does the initial unspecific response adjust to a more adequate response, which in turn either strongly related to spiking activity when low-frequency pulses were applied or depended on the incoming activity when high-frequency pulse bursts were presented. Thus, only the development of BOLD responses during repetitive stimulations can predict the underlying neuronal activity and deconvolution analysis should not be performed during an initial stimulation period.

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NMDA-Dependent Mechanisms Only Affect the BOLD Response in the Rat Dentate Gyrus by Modifying Local Signal Processing

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.182 ◽

2011 ◽

Vol 32 (3) ◽

pp. 570-584 ◽

Cited By ~ 3

Author(s):

Regina Tiede ◽

Karla Krautwald ◽

Anja Fincke ◽

Frank Angenstein

Keyword(s):

Signal Processing ◽

Nmda Receptor ◽

Dentate Gyrus ◽

Entorhinal Cortex ◽

Bold Response ◽

Electrophysiological Response ◽

Perforant Pathway ◽

Bold Responses ◽

The Right ◽

Stimulation Of

The role of N-methyl-d-aspartate (NMDA) receptor-mediated mechanisms in the formation of a blood oxygen level-dependent (BOLD) response was studied using electrical stimulation of the right perforant pathway. Stimulation of this fiber bundle triggered BOLD responses in the right hippocampal formation and in the left entorhinal cortex. The perforant pathway projects to and activates the dentate gyrus monosynaptically, activation in the contralateral entorhinal cortex is multisynaptic and requires forwarding and processing of signals. Application of the NMDA receptor antagonist MK801 during stimulation had no effect on BOLD responses in the right dentate gyrus, but reduced the BOLD responses in the left entorhinal cortex. In contrast, application of MK801 before the first stimulation train reduced the BOLD response in both regions. Electrophysiological recordings revealed that the initial stimulation trains changed the local processing of the incoming signals in the dentate gyrus. This altered electrophysiological response was not further changed by a subsequent application of MK801, which is in agreement with an unchanged BOLD response. When MK801 was present during the first stimulation train, a dissimilar electrophysiological response pattern was observed and corresponds to an altered BOLD response, indicating that NMDA-dependent mechanisms indirectly affect the BOLD response, mainly via modifying local signal processing and subsequent propagation.

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Low Frequency Stimulation of the Perforant Pathway Generates Anesthesia-Specific Variations in Neural Activity and BOLD Responses in the Rat Dentate Gyrus

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.126 ◽

2011 ◽

Vol 32 (2) ◽

pp. 291-305 ◽

Cited By ~ 12

Author(s):

Karla Krautwald ◽

Frank Angenstein

Keyword(s):

Dentate Gyrus ◽

Stimulus Frequency ◽

Low Frequency ◽

Blood Oxygen Level Dependent ◽

Bold Response ◽

Blood Oxygen Level ◽

Perforant Pathway ◽

Bold Responses ◽

Dependent Signal ◽

Frequency Stimulation

To study how various anesthetics affect the relationship between stimulus frequency and generated functional magnetic resonance imaging (fMRI) signals in the rat dentate gyrus, the perforant pathway was electrically stimulated with repetitive low frequency (i.e., 0.625, 1.25, 2.5, 5, and 10 Hz) stimulation trains under isoflurane/N2O, isoflurane, medetomidine, and α-chloralose. During stimulation, the blood oxygen level-dependent signal intensity (BOLD response) and local field potentials in the dentate gyrus were simultaneously recorded to prove whether the present anesthetic controls the generation of a BOLD response via targeting general hemodynamic parameters, by affecting mechanisms of neurovascular coupling, or by disrupting local signal processing. Using this combined electrophysiological/fMRI approach, we found that the threshold frequency (i.e., the minimal frequency required to trigger significant BOLD responses), the optimal frequency (i.e., the frequency that elicit the strongest BOLD response), and the spatial distribution of generated BOLD responses are specific for each anesthetic used. Concurrent with anesthetic-dependent characteristics of the BOLD response, we found the pattern of stimulus-induced neuronal activity in the dentate gyrus is also specific for each anesthetic. Consequently, the anesthetic-specific influence on local signaling processes is the underlying cause for the observation that an identical stimulus elicits different BOLD responses under various anesthetics.

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Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous PET-fMRI

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2021913118 ◽

2021 ◽

Vol 118 (27) ◽

pp. e2021913118

Author(s):

Lars Jonasson Stiernman ◽

Filip Grill ◽

Andreas Hahn ◽

Lucas Rischka ◽

Rupert Lanzenberger ◽

...

Keyword(s):

Glucose Metabolism ◽

Cognitive Control ◽

Default Mode Network ◽

Blood Oxygenation ◽

Bold Response ◽

Hybrid Functional ◽

Default Mode ◽

Bold Responses ◽

Negative Bold ◽

And Task

The finding of reduced functional MRI (fMRI) activity in the default mode network (DMN) during externally focused cognitive control has been highly influential to our understanding of human brain function. However, these negative fMRI responses, measured as relative decreases in the blood-oxygenation-level–dependent (BOLD) response between rest and task, have also prompted major questions of interpretation. Using hybrid functional positron emission tomography (PET)-MRI, this study shows that task-positive and -negative BOLD responses do not reflect antagonistic patterns of synaptic metabolism. Task-positive BOLD responses in attention and control networks were accompanied by concomitant increases in glucose metabolism during cognitive control, but metabolism in widespread DMN remained high during rest and task despite negative BOLD responses. Dissociations between glucose metabolism and the BOLD response specific to the DMN reveal functional heterogeneity in this network and demonstrate that negative BOLD responses during cognitive control should not be interpreted to reflect relative increases in metabolic activity during rest. Rather, neurovascular coupling underlying BOLD response patterns during rest and task in DMN appears fundamentally different from BOLD responses in other association networks during cognitive control.

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On the origin of sustained negative BOLD response

Journal of Neurophysiology ◽

10.1152/jn.01199.2011 ◽

2012 ◽

Vol 108 (9) ◽

pp. 2339-2342 ◽

Cited By ~ 14

Author(s):

Marta Moraschi ◽

Mauro DiNuzzo ◽

Federico Giove

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Functional Magnetic Resonance Imaging ◽

Neuronal Activity ◽

Neural Activity ◽

Brain Regions ◽

Bold Response ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Negative Bold

Several brain regions exhibit a sustained negative BOLD response (NBR) during specific tasks, as assessed with functional magnetic resonance imaging. The origin of the NBR and the relationships between the vascular/metabolic dynamics and the underlying neural activity are highly debated. Converging evidence indicates that NBR, in human and non-human primates, can be interpreted in terms of decrease in neuronal activity under its basal level, rather than a purely vascular phenomenon. However, the scarcity of direct experimental evidence suggests caution and encourages the ongoing utilization of multimodal approaches in the investigation of this effect.

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Low frequency pulse stimulation of Schaffer collaterals in Trpm4−/− knockout rats differently affects baseline BOLD signals in target regions of the right hippocampus but not BOLD responses at the site of stimulation

NeuroImage ◽

10.1016/j.neuroimage.2018.12.020 ◽

2019 ◽

Vol 188 ◽

pp. 347-356 ◽

Cited By ~ 4

Author(s):

Marta Bovet-Carmona ◽

Karla Krautwald ◽

Aurélie Menigoz ◽

Rudi Vennekens ◽

Detlef Balschun ◽

...

Keyword(s):

Low Frequency ◽

Schaffer Collaterals ◽

Bold Responses ◽

The Right ◽

Pulse Stimulation ◽

Site Of Stimulation ◽

Frequency Pulse ◽

Stimulation Of

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A dynamical model of the laminar BOLD response

10.1101/609099 ◽

2019 ◽

Cited By ~ 5

Author(s):

Martin Havlicek ◽

Kamil Uludag

Keyword(s):

High Resolution ◽

Blood Volume ◽

Neuronal Activity ◽

Cerebral Blood Volume ◽

Local Maximum ◽

Mass Conservation ◽

Physiological Parameters ◽

Blood Oxygenation ◽

Bold Signal ◽

Bold Response

AbstractHigh-resolution functional magnetic resonance imaging (fMRI) using blood oxygenation dependent level-dependent (BOLD) signal is an increasingly popular tool to non-invasively examine neuronal processes at the mesoscopic level. However, as the BOLD signal stems from hemodynamic changes, its temporal and spatial properties do not match those of the underlying neuronal activity. In particular, the laminar BOLD response (LBR), commonly measured with gradient-echo (GE) MRI sequence, is confounded by non-local changes in deoxygenated hemoglobin and cerebral blood volume propagated within intracortical ascending veins, leading to a unidirectional blurring of the neuronal activity distribution towards the cortical surface. Here, we present a new cortical depth-dependent model of the BOLD response based on the principle of mass conservation, which takes the effect of ascending (and pial) veins on the cortical BOLD responses explicitly into account. It can be used to dynamically model cortical depth profiles of the BOLD signal as a function of various baseline- and activity-related physiological parameters for any spatiotemporal distribution of neuronal changes. We demonstrate that the commonly observed spatial increase of LBR is mainly due to baseline blood volume increase towards the surface. In contrast, an occasionally observed local maximum in the LBR (i.e. the so-called “bump”) is mainly due to spatially inhomogeneous neuronal changes rather than locally higher baseline blood volume. In addition, we show that the GE-BOLD signal laminar point-spread functions, representing the signal leakage towards the surface, depend on several physiological parameters and on the level of neuronal activity. Furthermore, even in the case of simultaneous neuronal changes at each depth, inter-laminar delays of LBR transients are present due to the ascending vein. In summary, the model provides a conceptual framework for the biophysical interpretation of common experimental observations in high-resolution fMRI data. In the future, the model will allow for deconvolution of the spatiotemporal hemodynamic bias of the LBR and provide an estimate of the underlying laminar excitatory and inhibitory neuronal activity.

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