Spatiotemporal Evolution of Functional Hemodynamic Changes and Their Relationship to Neuronal Activity

Abstract

Brain imaging techniques such as functional magnetic resonance imaging (fMRI) have provided a wealth of information about brain organization, but their ability to investigate fine-scale functional architecture is limited by the spatial specificity of the hemodynamic responses upon which they are based. We investigated the spatiotemporal evolution of hemodynamic responses in rat somatosensory cortex to electrical hindpaw stimulation. We combined the advantages of optical intrinsic signal imaging and spectroscopy to produce high-resolution two-dimensional maps of functional changes in tissue oxygenation and blood volume. Cerebral blood flow changes were measured with laser-Doppler flowmetry, and simultaneously recorded field potentials allowed comparison between hemodynamic changes and underlying neuronal activity. For the first 2 to 3 secs of activation, hemodynamic responses overlapped in a central parenchymal focus. Over the next several seconds, cerebral blood volume changes propagated retrograde into feeding arterioles, and oxygenation changes anterograde into draining veins. By 5 to 6 secs, responses localized primarily in vascular structures distant from the central focus. The peak spatial extent of the hemodynamic response increased linearly with synaptic activity. This spatial spread might be because of lateral subthreshold activation or passive vascular overspill. These results imply early microvascular changes in volume and oxygenation localize to activated neural columns, and that spatial specificity will be optimal within a 2-to 3-sec window after neuronal activation.

Two-photon imaging of cerebral hemodynamics and neural activity in awake and anesthetized marmosets

“…The hemodynamic response signal reached its peak value 4–5 s following the stimulus onset (Silva et al, 2011). In humans, BOLD fMRI times-to-peak are 5–7 s (Aguirre et al, 1998; Friston et al, 1995; Boynton et al, 1996), while in anesthetized rodents they can range from 2.5 to 5 s, depending on the imaging modality (Tian et al, 2010; Berwick et al, 2005; Martindale et al, 2003; Chen et al, 2009; Chen et al, 2011; Narayan et al, 1994; Sheth et al, 2005). This indicates that the cortical microvascular length in marmosets may be more similar to humans than to rodents, presenting an elongated dispersive contribution of the transit of deoxyhemoglobin through the post-capillary side of the cerebral vasculature.…”

Hyperspectral optical tomography of intrinsic signals in the rat cortex

“…[29][30][31] Other methods have used a filter wheel or flashing LEDs to serially obtain images at multiple wavelengths. [32][33][34] While effective, these methods are limited by the trade-off between the number of wavelengths measured and temporal resolution. Recent attempts to overcome these limitations include approaches using a combination of beam splitters and filters to image at four wavelengths simultaneously 35 and methods using concurrent CCD-based imaging and fiberbased spectroscopy in a single experiment.…”

Dynamic Magnetic Resonance Imaging of Cerebral Blood Flow Using Arterial Spin Labeling

“…The increased hyperoxygenation becomes prominent in medium to large draining veins, and thus this response is often considered to be spatially nonspecific. Upon cessation of the increased electrical activity, the neurovascular coupling causes restoration of the capillary and arteriolar volume, resulting in restoration of local CBF and of the imaging signal, once the transit of oxyhemoglobin across the local cerebral vasculature is completed (40). Thus, the temporal resolution of neuroimaging techniques is limited by vascular transit times.…”

“…Thus, the temporal resolution of neuroimaging techniques is limited by vascular transit times. Recently, much effort has been placed on determining the “hemodynamic impulse response” (HIR) function as a way to understand the minimal evolution of vascular events and so that responses to complex neural activity can be modeled and predicted (40–45). For example, in rats, the OIS response to a 2-s-long whisker or forepaw stimulus begins 0.5–1 s after stimulus onset, peaks at 2.5–3 s, and returns to baseline by 4–5 s (40,42–46).…”

“…Recently, much effort has been placed on determining the “hemodynamic impulse response” (HIR) function as a way to understand the minimal evolution of vascular events and so that responses to complex neural activity can be modeled and predicted (40–45). For example, in rats, the OIS response to a 2-s-long whisker or forepaw stimulus begins 0.5–1 s after stimulus onset, peaks at 2.5–3 s, and returns to baseline by 4–5 s (40,42–46). In humans, the full-width-at-half-maximum (FWHM) is 5–7 s (47–49), and can be improved to 3–4 s if the contribution from large vessels is removed (50).…”