Early and Late Stimulus-Evoked Cortical Hemodynamic Responses Provide Insight into the Neurogenic Nature of Neurovascular Coupling

Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained from modern neuroimaging techniques. This study investigated the hemodynamic and neural responses in rat somatosensory cortex elicited by 16 seconds electrical whisker stimuli. Hemodynamics were measured by optical imaging spectroscopy and neural activity by multichannel electrophysiology. Previous studies have suggested that the whisker-evoked hemodynamic response contains two mechanisms, a transient ‘backwards’ dilation of the middle cerebral artery, followed by an increase in blood volume localized to the site of neural activity. To distinguish between the mechanisms responsible for these aspects of the response, we presented whisker stimuli during normocapnia (‘control’), and during a high level of hypercapnia. Hypercapnia was used to ‘predilate’ arteries and thus possibly ‘inhibit’ aspects of the response related to the ‘early’ mechanism. Indeed, hemodynamic data suggested that the transient stimulus-evoked response was absent under hypercapnia. However, evoked neural responses were also altered during hypercapnia and convolution of the neural responses from both the normocapnic and hypercapnic conditions with a canonical impulse response function, suggested that neurovascular coupling was similar in both conditions. Although data did not clearly dissociate early and late vascular responses, they suggest that the neurovascular coupling relationship is neurogenic in origin.

[1]  M. Wong-Riley,et al.  Histochemical changes in cytochrome oxidase of cortical barrels after vibrissal removal in neonatal and adult mice. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[2]  M M Mesulam,et al.  Report of IFCN Committee on Basic Mechanisms. Basic mechanisms of cerebral rhythmic activities. , 1990, Electroencephalography and clinical neurophysiology.

[3]  F. L. D. Silva,et al.  Basic mechanisms of cerebral rhythmic activities , 1990 .

[4]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  A. Nuñez,et al.  Unit activity of rat basal forebrain neurons: Relationship to cortical activity , 1996, Neuroscience.

[6]  A. Villringer,et al.  Excessive oxygen or glucose supply does not alter the blood flow response to somatosensory stimulation or spreading depression in rats , 1997, Brain Research.

[7]  A. Angel,et al.  The effect of chemoreceptor stimulation on the centripetal transfer of somatosensory information in the urethane-anaesthetized rat , 1998, Neuroscience.

[8]  Elliot A Stein,et al.  Regional cerebral blood flow responses to variable frequency whisker stimulation: an autoradiographic analysis , 2000, Brain Research.

[9]  Ying Zheng,et al.  The Hemodynamic Impulse Response to a Single Neural Event , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  W. Webb,et al.  Neural Activity Triggers Neuronal Oxidative Metabolism Followed by Astrocytic Glycolysis , 2004, Science.

[11]  M. Castro-Alamancos Dynamics of sensory thalamocortical synaptic networks during information processing states , 2004, Progress in Neurobiology.

[12]  Peter Redgrave,et al.  Nonlinear coupling of neural activity and CBF in rodent barrel cortex , 2004, NeuroImage.

[13]  Nikos K Logothetis,et al.  On the nature of the BOLD fMRI contrast mechanism. , 2004, Magnetic resonance imaging.

[14]  John E. W. Mayhew,et al.  The effect of hypercapnia on the neural and hemodynamic responses to somatosensory stimulation , 2005, NeuroImage.

[15]  J. Mayhew,et al.  Concurrent fMRI and optical measures for the investigation of the hemodynamic response function , 2005, Magnetic resonance in medicine.

[16]  Ying Zheng,et al.  Long Duration Stimuli and Nonlinearities in the Neural–Haemodynamic Coupling , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  N. McLoughlin,et al.  Neurovascular coupling investigated with two‐dimensional optical imaging spectroscopy in rat whisker barrel cortex , 2005, The European journal of neuroscience.

[18]  N. Logothetis,et al.  Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1 , 2006, Nature Neuroscience.

[19]  C. Iadecola,et al.  Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. , 2006, Journal of applied physiology.

[20]  D. Kleinfeld,et al.  Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-Dependent Signal , 2007, The Journal of Neuroscience.

[21]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[22]  J. Mayhew,et al.  Fine detail of neurovascular coupling revealed by spatiotemporal analysis of the hemodynamic response to single whisker stimulation in rat barrel cortex. , 2008, Journal of neurophysiology.

[23]  Ying Zheng,et al.  Theory and generalization of monte carlo models of the BOLD signal source , 2008, Magnetic resonance in medicine.

[24]  N. Logothetis,et al.  The Influence of Moderate Hypercapnia on Neural Activity in the Anesthetized Nonhuman Primate , 2008, Cerebral cortex.

[25]  P. Carmeliet,et al.  Neurovascular signalling defects in neurodegeneration , 2008, Nature Reviews Neuroscience.

[26]  Grant R. Gordon,et al.  Brain metabolism dictates the polarity of astrocyte control over arterioles , 2008, Nature.

[27]  P. Moreira,et al.  Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. , 2008, Free radical biology & medicine.

[28]  Peter Redgrave,et al.  Altered neurovascular coupling during information‐processing states , 2008, The European journal of neuroscience.

[29]  D. Kleinfeld,et al.  Stimulus-Induced Changes in Blood Flow and 2-Deoxyglucose Uptake Dissociate in Ipsilateral Somatosensory Cortex , 2008, The Journal of Neuroscience.

[30]  Yevgeniy B. Sirotin,et al.  Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity. , 2009, Nature.

[31]  M. Castro-Alamancos,et al.  Cortical up and Activated States: Implications for Sensory Information Processing Synaptic Conductance Increases during up States , 2022 .

[32]  P. Bandettini,et al.  What's New in Neuroimaging Methods? , 2009, Annals of the New York Academy of Sciences.

[33]  Wiring and Plumbing in the Brain , 2009, Frontiers in human neuroscience.

[34]  John E. W. Mayhew,et al.  Refinement of optical imaging spectroscopy algorithms using concurrent BOLD and CBV fMRI , 2009, NeuroImage.

[35]  H. Slovin,et al.  A BOLD Assumption , 2010, Front. Neuroenerg..

[36]  Andreas Kleinschmidt,et al.  The Blind, the Lame, and the Poor Signals of Brain Function—a Comment on Sirotin and Das (2009) , 2022 .

[37]  D. Johnston,et al.  Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling , 2010, The Journal of Neuroscience.

[38]  N. Logothetis Neurovascular Uncoupling: Much Ado about Nothing , 2010, Front. Neuroenerg..

[39]  Myles Jones,et al.  Temporal coupling between stimulus-evoked neural activity and hemodynamic responses from individual cortical columns , 2010, Physics in medicine and biology.

[40]  Dmitriy A Yablonskiy,et al.  Cerebral metabolic rate in hypercapnia: Controversy continues , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  David Kleinfeld,et al.  A Guide to Delineate the Logic of Neurovascular Signaling in the Brain , 2010, Front. Neuroenerg..

[42]  E. Halgren,et al.  Depression of cortical activity in humans by mild hypercapnia , 2012, Human brain mapping.