Abstract
Diffusion functional MRI (DfMRI) reveals neuronal activation even when neurovascular coupling is abolished, contrary to blood oxygenation level—dependent (BOLD) functional MRI (fMRI). Here, we show that the water apparent diffusion coefficient (ADC) derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity observed with local field potentials (LFPs), especially in regions involved in wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting systemic effects of the anesthesia on overall brain hemodynamics status. Electrical stimulation of the central medial thalamus nucleus (CM) exhibiting this anesthesia-induced ADC increase led the animals to transiently wake up. Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the ADC to increase further locally, although LFP activity remained unchanged, and increased the current threshold awakening the animals under CM electrical stimulation. Oppositely, induction of cell swelling in the CM through infusion of a hypotonic solution (−80 milliosmole [mOsm] artificial cerebrospinal fluid [aCSF]) led to a local ADC decrease and a lower current threshold to wake up the animals. Strikingly, the local ADC changes produced by blocking or enhancing cell swelling in the CM were also mirrored remotely in areas functionally connected to the CM, such as the cingulate and somatosensory cortex. Together, those results strongly suggest that neuronal swelling is a significant mechanism underlying DfMRI.
Highlights
Diffusion functional MRI (DfMRI) [1,2] has been proposed as an imaging method to investigate brain function noninvasively, an alternative to blood oxygenation level—dependent (BOLD) functional MRI [3], which has been extensively used to investigate brain activity [4]
This new approach, known as diffusion functional MRI (DfMRI), has high potential for functional imaging of the brain, as the currently widespread blood oxygenation level—dependent (BOLD)-functional MRI method, which is based on neurovascular coupling, remains an indirect marker of neuronal activation
We show that the water apparent diffusion coefficient (ADC) derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity, especially in regions involved in wakefulness
Summary
Diffusion functional MRI (DfMRI) [1,2] has been proposed as an imaging method to investigate brain function noninvasively, an alternative to blood oxygenation level—dependent (BOLD) functional MRI (fMRI) [3], which has been extensively used to investigate brain activity [4]. Diffusion MRI is thought to be more directly linked to neuronal activation, as the diffusion MRI signal is exquisitely sensitive to minute changes, such as cell swelling, occurring in the tissue microstructure upon various physiological or pathological changes [8]. To check the hypothesis that the water apparent diffusion coefficient (ADC) measured with DfMRI provides a direct, quantitative assessment of neural states of activity or deactivity and to shed light on the DfMRI mechanisms, we have investigated the functional features of rat brain loci undergoing ADC variations using electrophysiological recordings and electrical stimulation, as well as pharmacological challenges interfering with cell swelling, under various anesthetic or sedative conditions, using several doses of an anesthetic drug, isoflurane, and a sedative drug, medetomidine—two drugs widely used in preclinical MRI studies
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