Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model

Abe, Yoshifumi; Takata, Norio; Hamada, Hiro Taiyo; Hiraoka, Yuichi; Aida, Tomomi; Bihan, Denis Le; Doya, Kenji; Tanaka, Kenji F.

doi:10.1016/j.neuroimage.2020.117318

Cited by 13 publications

(11 citation statements)

References 52 publications

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“…Second, and most importantly for our purposes, this difference in RS-FC patterns between BOLD and dfMRI suggests that there is no twin of negative BOLD in dfMRI and that the sources of dfMRI signal are distinct from those of BOLD and largely free of vascular contributions, in agreement with previous findings in the rat brain (45, 46). Indeed, from the perspective of neuron microstructural fluctuations, inhibitory activity leading to membrane hyperpolarization is not expected to alter the cell volume and/or morphology substantially relative to baseline – i.e.…”

Section: Discussionsupporting

confidence: 91%

Beyond BOLD: Evidence for diffusion fMRI contrast in the human brain distinct from neurovascular response

Olszowy¹,

Diao

Jelescu³

2021

Preprint

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Functional Magnetic Resonance Imaging (fMRI) is an essential method to measure brain activity non-invasively. While fMRI almost systematically relies on the blood oxygenation level-dependent (BOLD) contrast, there is an increasing interest in alternative methods that would not rely on neurovascular coupling. A promising but controversial such alternative is diffusion fMRI (dfMRI), which relies instead on dynamic fluctuations in apparent diffusion coefficient (ADC) due to microstructural changes underlying neuronal activity. However, it is unclear whether genuine dfMRI contrast, distinct from BOLD contamination, can be detected in the human brain in physiological conditions. Here, we present the first dfMRI study in humans attempting to minimize all BOLD contamination sources and comparing functional responses at two field strengths (3T and 7T), both for task and resting-state (RS) fMRI. Our study benefits from unprecedented high spatiotemporal resolution and harnesses novel denoising strategies. We report task-induced decrease in ADC with temporal and spatial features distinct from the BOLD response and yielding more specific activation maps. Furthermore, we report dfMRI RS connectivity which, compared to its BOLD counterpart, is essentially free from physiological artifacts and preserves positive correlations but preferentially suppresses anti-correlations, which are likely of vascular origin. A careful acquisition and processing design thus enable the detection of genuine dfMRI contrast on clinical MRI systems. As opposed to BOLD, diffusion functional contrast could be particularly well suited for low-field MRI.

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Section: Discussionsupporting

confidence: 91%

Beyond BOLD: Evidence for diffusion fMRI contrast in the human brain distinct from neurovascular response

Olszowy¹,

Diao

Jelescu³

2021

Preprint

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“…Astrocyte glutamate transporters dissipate excitatory neurotransmission to protect neurons from excessive synaptic glutamate exposure (Bylicky, Mueller, & Day, 2018). Loss of GLT-1 function causes abnormal brain network activity on diffusion functional MRI (Abe et al, 2020).…”

Section: Astrocytesmentioning

confidence: 99%

Fractional anisotropy from diffusion tensor imaging correlates with acute astrocyte and myelin swelling in neonatal swine models of excitotoxic and hypoxic‐ischemic brain injury

et al. 2021

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The specific cytopathology that causes abnormal fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI) after neonatal hypoxia‐ischemia (HI) is not completely understood. The panoply of cell types in the brain might contribute differentially to changes in DTI metrics. Because glia are the predominant cell type in brain, we hypothesized that changes in FA and MD would signify perturbations in glial microstructure. Using a 3‐Tesla clinical scanner, we conducted in vivo DTI MRI in nine neonatal piglets at 20–96 h after excitotoxic brain injury from striatal quinolinic acid injection or global HI. FA and MD from putamen, caudate, and internal capsule in toto were correlated with astrocyte swelling, neuronal excitotoxicity, and white matter injury. Low FA correlated with more swollen astrocytes immunophenotyped by aquaporin‐4 (AQP4), glial fibrillary acidic protein (GFAP), and glutamate transporter‐1 (GLT‐1). Low FA was also related to the loss of neurons with perineuronal GLT‐1+ astrocyte decorations, large myelin swellings, lower myelin density, and oligodendrocyte cell death identified by 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase, bridging integrator‐1, and nuclear morphology. MD correlated with degenerating oligodendrocytes and depletion of normal GFAP+ astrocytes but not with astrocyte or myelin swelling. We conclude that FA is associated with cytotoxic edema in astrocytes and oligodendrocyte processes as well as myelin injury at the cellular level. MD can detect glial cell death and loss, but it may not discern subtle pathology in swollen astrocytes, oligodendrocytes, or myelin. This study provides a cytopathologic basis for interpreting DTI in the neonatal brain after HI.

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“…A previous optogenetic fMRI experiment activated DRN serotonin neurons using the Pet1 promoter under anesthesia and showed widespread suppression of cortical activities [9]. We introduced an acclimation protocol to allow stable fMRI recording from awake mice [1,42] and found that DRN serotonin activation in an awake state induced a brain-wide activity increase in reward-related areas, both in the cortical and subcortical areas. In contrast, under anesthesia with isoflurane, DRN serotonin activation decreased activities in those areas, consistent with a previous study [9].…”

Section: /35mentioning

confidence: 98%

“…In order to habituate awake mice to the MRI imaging protocol, an acclimation protocol was applied to the mice after the surgeries for head-fixation [1,42]. Mice were fixed in a mock MRI environment and exposed to MRI imaging sounds and visual blue illumination for 2 h to habituate them to a leak of illumination during scanning (2.0 Hz).…”

Section: Acclimationmentioning

confidence: 99%

Optogenetic activation of dorsal raphe serotonin neurons induces a brain-wide response in reward network

Hamada

Abe

Takata

et al. 2022

Preprint

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Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects through its brain-wide projections and variety of receptors remains unclear. Here we measured the brain-wide response to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) by functional MRI using an 11.7T scanner with a cryoprobe. Transient activation of DRN serotonin neurons caused wide-spread activation of reward-related brain areas. The same stimulation under anesthesia with isoflurane decreased activation of those reward-related areas and the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 type receptors. The primarily facilitatory effect on reward-related brain areas by DRN serotonergic activation is consistent with recent discoveries of its roles in reward-oriented behaviors and demands reconsideration of inhibitory view due to the result under anesthesia.

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Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model

Cited by 13 publications

References 52 publications

Beyond BOLD: Evidence for diffusion fMRI contrast in the human brain distinct from neurovascular response

Beyond BOLD: Evidence for diffusion fMRI contrast in the human brain distinct from neurovascular response

Fractional anisotropy from diffusion tensor imaging correlates with acute astrocyte and myelin swelling in neonatal swine models of excitotoxic and hypoxic‐ischemic brain injury

Optogenetic activation of dorsal raphe serotonin neurons induces a brain-wide response in reward network

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