Abstract
Understanding the spatiotemporal features of the hemodynamic response function (HRF) to brain stimulation is essential for the correct application of neuroimaging methods to study brain function. Here, we investigated the spatiotemporal evolution of the blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) HRF in conscious, awake marmosets (Callithrix jacchus), a New World non-human primate with a lissencephalic brain and with growing use in biomedical research. The marmosets were acclimatized to head fixation and placed in a 7-T magnetic resonance imaging (MRI) scanner. Somatosensory stimulation (333-μs pulses; amplitude, 2mA; 64Hz) was delivered bilaterally via pairs of contact electrodes. A block design paradigm was used in which the stimulus duration increased in pseudo-random order from a single pulse up to 256 electrical pulses (4s). For CBV measurements, 30mg/kg of ultrasmall superparamagnetic ironoxide particles (USPIO) injected intravenously, were used. Robust BOLD and CBV HRFs were obtained in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2) and caudate at all stimulus conditions. In particular, BOLD and CBV responses to a single 333-μs-long stimulus were reliably measured, and the CBV HRF presented shorter onset time and time to peak than the BOLD HRF. Both the size of the regions of activation and the peak amplitude of the HRFs grew quickly with increasing stimulus duration, and saturated for stimulus durations greater than 1s. Onset times in S1 and S2 were faster than in caudate. Finally, the fine spatiotemporal features of the HRF in awake marmosets were similar to those obtained in humans, indicating that the continued refinement of awake non-human primate models is essential to maximize the applicability of animal functional MRI studies to the investigation of human brain function.
Highlights
The spatiotemporal characteristics of the hemodynamic response function (HRF) to focal changes in neural activity limit the resolution of functional neuroimaging techniques such as blood oxygenation level-dependent (BOLD) fMRI
We investigate the spatiotemporal evolution of the BOLD and cerebral blood volume (CBV) HRF to somatosensory stimulation in conscious awake marmosets (Callithrix jacchus), a New World non-human primate with a brain size equivalent to the relative brain size of humans and approximately five times larger than the rat brain
The onset time of the BOLD HRF in S1 and S2 were faster than in caudate, which is consistent with some degree of serial processing between S1 and S2, and as expected, with thalamocortical processing preceding cortico-striatal processing
Summary
The spatiotemporal characteristics of the hemodynamic response function (HRF) to focal changes in neural activity limit the resolution of functional neuroimaging techniques such as BOLD fMRI. In typical fMRI experiments, the stimulus is presented according to a block design paradigm in which periods of rest and stimulation are alternated. Because the cerebral vasculature is a continuous, yet distributed network 3, the stimulus duration strongly influences the spatiotemporal characteristics of the HRF. Brief stimuli elicit vascular responses that consist mainly of dilatation of local capillaries and arterioles [4,5], which leads to local increases in cerebral blood volume (CBV) and flow (CBF), and an inflow of oxyhemoglobin and concomitant displacement of deoxyhemoglobin in the venules and veins, causing a BOLD effect 6. Proper understanding of the influence of the stimulus duration on the spatiotemporal features of the HRF is essential to both designs of functional neuroimaging experiments and interpretation of data
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