Functional ultrasound reveals effects of MRI acoustic noise on brain function

Loud acoustic noise from the scanner during functional magnetic resonance imaging (fMRI) can affect functional connectivity (FC) observed in the resting state, but the exact effect of the MRI acoustic noise on resting state FC is not well understood. Functional ultrasound (fUS) is a neuroimaging method that visualizes brain activity based on relative cerebral blood volume (rCBV), a similar neurovascular coupling response to that measured by fMRI, but without the audible acoustic noise. In this study, we investigated the effects of different acoustic noise levels (silent, 80 dB, and 110 dB) on FC by measuring resting state fUS (rsfUS) in awake mice in an environment similar to fMRI measurement. Then, we compared the results to those of resting state fMRI (rsfMRI) conducted using an 11.7 Tesla scanner. RsfUS experiments revealed a significant reduction in FC between the retrosplenial dysgranular and auditory cortexes (0.56 ± 0.07 at silence vs 0.05 ± 0.05 at 110 dB, p=.01) and a significant increase in FC anticorrelation between the infralimbic and motor cortexes (−0.21 ± 0.08 at silence vs −0.47 ± 0.04 at 110 dB, p=.017) as acoustic noise increased from silence to 80 dB and 110 dB, with increased consistency of FC patterns between rsfUS and rsfMRI being found with the louder noise conditions. Event-related auditory stimulation experiments using fUS showed strong positive rCBV changes (16.5% ± 2.9% at 110 dB) in the auditory cortex, and negative rCBV changes (−6.7% ± 0.8% at 110 dB) in the motor cortex, both being constituents of the brain network that was altered by the presence of acoustic noise in the resting state experiments. Anticorrelation between constituent brain regions of the default mode network (such as the infralimbic cortex) and those of task-positive sensorimotor networks (such as the motor cortex) is known to be an important feature of brain network antagonism, and has been studied as a biological marker of brain disfunction and disease. This study suggests that attention should be paid to the acoustic noise level when using rsfMRI to evaluate the anticorrelation between the default mode network and task-positive sensorimotor network.journal articl

Potential of Multiscale Astrocyte Imaging for Revealing Mechanisms Underlying Neurodevelopmental Disorders

Astrocytes provide trophic and metabolic support to neurons and modulate circuit formation during development. In addition, astrocytes help maintain neuronal homeostasis through neurovascular coupling, blood–brain barrier maintenance, clearance of metabolites and nonfunctional proteins via the glymphatic system, extracellular potassium buffering, and regulation of synaptic activity. Thus, astrocyte dysfunction may contribute to a myriad of neurological disorders. Indeed, astrocyte dysfunction during development has been implicated in Rett disease, Alexander’s disease, epilepsy, and autism, among other disorders. Numerous disease model mice have been established to investigate these diseases, but important preclinical findings on etiology and pathophysiology have not translated into clinical interventions. A multidisciplinary approach is required to elucidate the mechanism of these diseases because astrocyte dysfunction can result in altered neuronal connectivity, morphology, and activity. Recent progress in neuroimaging techniques has enabled noninvasive investigations of brain structure and function at multiple spatiotemporal scales, and these technologies are expected to facilitate the translation of preclinical findings to clinical studies and ultimately to clinical trials. Here, we review recent progress on astrocyte contributions to neurodevelopmental and neuropsychiatric disorders revealed using novel imaging techniques, from microscopy scale to mesoscopic scale

Micro-magnetic resonance imaging of ex vivo mouse embryos with potato starch suspension

Summary: Potato starch suspension (PSS) holds promise as a solution to issues, such as air bubbles and specimen motion, associated with micro-magnetic resonance imaging (micro-MRI) of ex vivo embryos. Here, we present a protocol for using PSS when scanning specimens with micro-MRI. We describe steps for preparing samples and potato starch with phosphate-buffered saline. We then detail steps for specimen immersion and micro-MRI scanning. This protocol will enable micro-MRI of not only embryos but also other specimens, such as insects.For complete details on the use and execution of this protocol, please refer to Tsurugizawa et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

The impact of fasting on resting state brain networks in mice

Abstract Fasting is known to influence learning and memory in mice and alter the neural networks that subserve these cognitive functions. We used high-resolution functional MRI to study the impact of fasting on resting-state functional connectivity in mice following 12 h of fasting. The cortex and subcortex were parcellated into 52 subregions and functional connectivity was measured between each pair of subregions in groups of fasted and non-fasted mice. Functional connectivity was globally increased in the fasted group compared to the non-fasted group, with the most significant increases evident between the hippocampus (bilateral), retrosplenial cortex (left), visual cortex (left) and auditory cortex (left). Functional brain networks in the non-fasted group comprised five segregated modules of strongly interconnected subregions, whereas the fasted group comprised only three modules. The amplitude of low frequency fluctuations (ALFF) was decreased in the ventromedial hypothalamus in the fasted group. Correlation in gamma oscillations derived from local field potentials was increased between the left visual and retrosplenial cortices in the fasted group and the power of gamma oscillations was reduced in the ventromedial hypothalamus. These results indicate that fasting induces profound changes in functional connectivity, most likely resulting from altered coupling of neuronal gamma oscillations

Spatial contribution of hippocampal BOLD activation in high-resolution fMRI

Abstract While the vascular origin of the BOLD-fMRI signal is established, the exact neurovascular coupling events contributing to this signal are still incompletely understood. Furthermore, the hippocampal spatial properties of the BOLD activation are not elucidated, although electrophysiology approaches have already revealed the precise spatial patterns of neural activity. High magnetic field fMRI offers improved contrast and allows for a better correlation with the underlying neuronal activity because of the increased contribution to the BOLD signal of small blood vessels. Here, we take advantage of these two benefits to investigate the spatial characteristics of the hippocampal activation in a rat model before and after changing the hippocampal plasticity by long-term potentiation (LTP). We found that the hippocampal BOLD signals evoked by electrical stimulation at the perforant pathway increased more at the radiatum layer of the hippocampal CA1 region than at the pyramidal cell layer. The return to the baseline of the hippocampal BOLD activation was prolonged after LTP induction compared with that before most likely due vascular or neurovascular coupling changes. Based on these results, we conclude that high resolution BOLD-fMRI allows the segregation of hippocampal subfields probably based on their underlying vascular or neurovascular coupling features

Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia

<div><p>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.</p></div

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.

The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its dysfunction might lead to several brain pathologies, including the Alzheimer's disease. A key component of the GS and brain tissue water circulation is the astrocyte which is regulated by acquaporin-4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo and non-invasively

Comparison of Apparent Diffusion Coefficient (ADC) and Blood Oxygenation Level—Dependent (BOLD) changes with Local Field Potentials (LFPs) in the Central Medial (CM) and Ventral Posterolateral (VPL) thalamic nuclei.

<p>BOLD changes under each dosage of isoflurane (A) and medetomidine (B) at the CM and the VPL. Region of interest (ROI) locations for the CM and the VPL are overlaid on structural images. ADC changes under each dosage of isoflurane (C) and medetomidine (D) at the CM and the VPL. (E) Representative LFP signals in a single animal at the CM (upper) and the VPL (below), for each dosage of isoflurane and medetomidine. Total LFP power (frequency range: 1–70 Hz) under each dosage of isoflurane (F; <i>n</i> = 8 for CM, <i>n</i> = 8 for VPL) and medetomidine (G; <i>n</i> = 8 for CM, <i>n</i> = 8 for VPL). Bar plots exhibit mean ± the standard error of the mean (SEM). * <i>p</i> < 0.05, ** <i>p</i> < 0.0, *** <i>p</i> < 0.001 (Paired <i>t</i>-test, versus low dose of each anesthesia). Data for the CM and the VPL of individual rats can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001494#pbio.2001494.s009" target="_blank">S1 Data</a> for ADC and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001494#pbio.2001494.s010" target="_blank">S2 Data</a> for BOLD. LFP power data for the CM and the VPL of individual rats can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001494#pbio.2001494.s012" target="_blank">S4 Data</a>.</p

Effects of H-80 infusion in the Central Medial thalamus nucleus (CM) on the Apparent Diffusion Coefficient (ADC), Local Field Potentials (LFPs) and awake response threshold.

<p>(A) Percentage of animals exhibiting an awake response during CM electrical stimulation after the CM infusion with −80 milliosmole (mOsm) hypotonic artificial cerebrospinal fluid (aCSF) (H-80; <i>n</i> = 6). (B) Average ADC change in the CM and cingulate cortex (Cg) before and after H-80 or aCSF infusion in the CM (<i>n</i> = 6 for each condition). Average time course of ADC change at the CM (C) and Cg (D) with the infusion of aCSF and H-80. (E) Representative local field potentials (LFP) signals at CM and Cg during CM infusion with aCSF (upper) or H-80 (low). (F) Total LFP power (frequency range: 1–70 Hz) in CM and Cg before and after CM infusion with H-80 (<i>n</i> = 6) or aCSF (<i>n</i> = 6). Time course and bar plots exhibit mean ± the standard error of the mean (SEM). ** <i>p</i> < 0.01 (Paired <i>t</i>-test between pre and post), # <i>p</i> < 0.05, ## <i>p</i> < 0.01 (Fisher’s exact test). Data for minimum amplitudes of individual rats can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001494#pbio.2001494.s013" target="_blank">S5 Data</a>. ADC data of individual rats found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001494#pbio.2001494.s011" target="_blank">S3 Data</a>. LFP power data can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2001494#pbio.2001494.s012" target="_blank">S4 Data</a>.</p