Time-dependent spatial specificity of high-resolution fMRI: insights into mesoscopic neurovascular coupling

Abstract

High-resolution functional magnetic resonance imaging (fMRI) is becoming increasingly popular because of the growing availability of ultra-high magnetic fields which are capable of improving sensitivity and spatial resolution. However, it is debatable whether increased spatial resolutions for haemodynamic-based techniques, like fMRI, can accurately detect the true location of neuronal activity. We have addressed this issue in functional columns and layers of animals with haemoglobin-based optical imaging and different fMRI contrasts, such as blood oxygenation level-dependent, cerebral blood flow and cerebral blood volume fMRI. In this review, we describe empirical evidence primarily from our own studies on how well these fMRI signals are spatially specific to the neuronally active site and discuss insights into neurovascular coupling at the mesoscale. This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.

Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing

“…The resolving power of laminar fMRI across different layers is closely dependent on fundamental CBV point spread and voxel resolution. Spatial specificity to neuronally active layers is improved with stimulation time up to ∼10 s ( 52 , 53 ), which may occur due to different dynamics of macro- and microvessels, fast-acting penetrating arterioles, and highly specific slow-responding capillaries ( 54 ). The CBV PSF was previously measured in the S1FL of mice with CBV-weighted optical-imaging ( 55 ) and in the rat olfactory bulb with CBV-weighted fMRI ( 56 ); the PSF was found to be ∼100 µm FWHM.…”

Dissection of brain-wide spontaneous and functional somatosensory circuits by fMRI with optogenetic silencing

“…The resolving power of laminar fMRI across different layers is closely dependent on fundamental CBV point spread and voxel resolution. Spatial specificity to neuronally active layers is improved with stimulation time up to ~10 s (66,67), which may occur due to different dynamics of macro-and microvessels, fast-acting penetrating arterioles and highly specific slow-responding capillaries (68).…”

Capillary responses to functional and pathological activations rely on the capillary states at rest

“…1 The fact that cerebral blood flow (CBF) is directed to the active regions based on neural activity (i.e., neurovascular coupling) allows us to map brain activity noninvasively using haemodynamic neuroimaging techniques. 2,3 Regional CBF is mainly regulated by parenchymal arterioles. 4,5 However, parenchymal arterioles develop independently of the functional neural unit, 6 suggesting that the capillary level of blood flow control further contributes to neurovascular coupling.…”

“…9 Using double-transgenic mice expressing genetically encoded calcium ion sensors (GCaMP) in cortical neurons (Cre-CaMKII), neural activity and microvasculature around activated neurons were imaged simultaneously with two-photon microscopy. Repeated 3D imaging (i.e., an XYZ scan) was performed at layers II/III in the somatosensory barrel cortex, while gradual changes in neural activity were induced by mechanical stimulation of contralateral whiskers with variable frequencies (1)(2)(3)(4)(5)(6)(7)(8) or by a seizure caused by kainic acid (a cyclic analogue of L-glutamate and an agonist of ionotropic kainic acid receptors 23 ). Trial-to-trial changes in capillary diameter were determined along the centreline of the vessel in the 3D reconstructed image, 9 resulting in big data (3000-5000 points per trial) that were used to estimate the probability distribution of the capillary responses to variable neural activations.…”