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

Abstract

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.

Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T

“…'Arterial' CBV a has a faster response and a faster post-stimulus baseline crossing, compared to the 'venous' CBV v response (Fig. 5B), as observed previously in animals (Kennerley et al, 2012a;Kim and Kim, 2011;Zong et al, 2012). 'Venous' ΔCBV v contribution appears negligibly small compared to ΔCBV tot (Fig.…”

“…Therefore, changes in 'venous' (65%-oxygenated) CBV, estimated in the proposed model, might arise to a small part from these arterioles as well as from capillaries, venules and veins. In arteries and arterioles during stimulation, the majority of the total CBV change occurs almost entirely due to an increase in the amount of fully oxygenated blood (Kennerley et al, 2012a). The CBV changes in post-arterial compartments, however, are likely to mostly contain 'venous' CBV.…”

Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex

“…The average LFP spikes did not change (from 92.6 ± 4.3 spikes per minute to 92.3 ± 3.3 spikes per minute) with PCO 2 (from 33 mmHg to 66 mmHg), indicating that neuronal LFPs are not sensitive to PCO 2 changes. This is consistent with the interpretation that the minimal effects of hypercapnia on Ca 2+ i LFOs reflect the widely held view that CO 2 in the range used here does not have large effects on neuronal activity or on neurovascular coupling (18)(19)(20).…”

“…This could be caused by the delays in the metabolic and vascular responses to the Ca 2+ increase or the transient time of hemoglobin through the vasculature, which is on the order of a few seconds (30). Indeed, in rodent models peak BOLD response occurs 4-6 s after the onset of stimulation (18,31).…”

“…In addition, local field potentials (LFPs) from neurons were measured to assess their correlations with the hemodynamic LFOs. Hypercapnia dilates cerebral blood vessels, increasing blood flow, but has minimal effects on neuronal activity (16,17) and neurovascular coupling (18)(19)(20). Thus, we used hypercapnia as a strategy to differentiate oscillatory components that are due to neurovascular coupling as opposed to other mechanisms that affect vascular tone.…”