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Brain or cardiovascular oscillation: ultra-slow oscillations under 0.01 Hz detected by resting-state fMRI
Patricia Pais Roldán1,2, Brian Edlow3, Johannes Stelzer1, Yuanyuan Jiang1, and Xin Yu1

1Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2Graduate Training Centre of Neuroscience, Tübingen, Germany, 3Massachusetts General Hospital, Boston, MA, United States

Synopsis

A high amplitude slow wave component of frequency 0.005 to 0.012 Hz was observed in multiple resting state fMRI scans of the rat brain under different anesthetics. These ultra-slow waves were localized predominantly in the hypothalamus. We hypothesize that these ultra-slow oscillations might have a neurological origin and may contribute to the analysis of resting state connectivity, which is currently limited to frequencies above 0.01 Hz . Future studies should investigate the origin of these oscillations with an independent measure (e.g. calcium imaging) and the implications of their incorporation into the analysis of rs-fMRI.

Introduction

Spectral analysis in resting-state fMRI (rs-fMRI) studies has mainly focused on the 0.01 to 0.1 Hz frequency range1-6. Frequencies under 0.01 Hz are typically regarded as artifacts from scanner instabilities or physiological noise7, and are routinely excluded from the rs-fMRI analysis. Here, we show robust ultra-slow rs-fMRI signal fluctuation of high regularity in the brain of rats receiving anesthesia. The frequency range of this ultra-slow oscillation (USO) is one order of magnitude lower than that of the motion artifacts caused by respiration-induced B0 fluctuation8 or the cardiovascular oscillations9,10. The predominance of USO in the hypothalamus indicates a potential relevance of these waves to the homeostatic regulation through the hypothalamic-pituitary-adrenal axis to control the autonomic nervous system11. The significance of this work is to show the dominating USO effect on the rs-fMRI, possibly indicating a peculiar brain state in animals with different anesthetics.

Methods

12 to 15 minutes of rs-fMRI data were acquired from anesthetized rats (under isoflurane, a-chloralose, medetomidine or urethane) using a 3D-EPI sequence with the following parameters: TE, 12.5 ms; TR, 31.25 ms (total TR, 1s); matrix size, 48x48x32; resolution, 400x400x600 µm (600 µm slice thickness). All images were acquired with a 12 cm diameter 14.1 T/26 cm magnet (Magnex, Oxford) interfaced to an Avance III console (Bruker, Ettlingen), capable of providing 100 G/cm with a rise time of 150 µs (Resonance Research). Trans-receiver surface coils with elliptical shape of ~ 2 x 3 cm minor and major axis, respectively, were used to acquire the whole brain fMRI. Animals were mechanically ventilated, and a low dose of the paralytic agent pancuronium was used to prevent motion artifacts. Frequency decomposition analysis and power estimation of the 0.005-0.012 Hz frequency band were performed to map the USO in the rat brain.

Results

We show that frequencies below the classical 0.01 Hz limit can be observed as high amplitude waves of rhythmic pattern in animals receiving anesthesia (Fig.1). The frequency of the high amplitude oscillations belonged to a range between 0.005 and 0.012 Hz. These USO occurred predominantly within the hypothalamus, as confirmed with bandpass power analysis (Fig.2).

Discussion

The features of the reported USO (brain region predominance, and especially, apparent absence of correlation with motion or physiological artifacts), may indicate that these oscillations have a neural origin instead of being derived from MR hardware noise. Furthermore, in contrast to the motion artifacts that are reliably detected from both blood pressure and fMRI time courses (Fig.3, arrows), a slow oscillation component as shown in the fMRI time course was not observed in the blood pressure records (Fig.3). Thus, the source of USO may not be directly contributed by cardiovascular fluctuations12, at least not due to blood pressure changes (Fig.3). Importantly, infraslow oscillations in a similar range were detected by EEG in brain-injured patients, which appeared related to modulations in the cortical excitability and have been hypothesized to emerge from a deep brain source13.

Conclusion

We detected an ultra-slow resting-state fMRI signal fluctuation in rats under different anesthetics, which was highlighted in the hypothalamic regions. Future work will aim to clarify the source of these oscillations with concurrent fMRI and calcium recordings in the hypothalamus in rats. In addition, different drugs to modulate the autonomous nervous system will be applied to specify the potential relevance to the cardiovascular function.

Acknowledgements

This work was supported by the Max-Planck-Society and the Graduate Training Centre of Neuroscience of Tübingen.

References

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Figures

Figure 1. Examples of slow oscillations detected under different anesthesia conditions.

Figure 2. Power of the 0.005 to 0.012 Hz band in the rat brain. Power of the band-pass filtered functional map averaged from 6 rats that presented slow oscillation time courses. Abbreviations: M: mammillary nuclei, LH: lateral hypothalamus.

Figure 3. Two examples showing blood pressure recordings during acquisition of rs-fMRI. Slow oscillations were not observed in the blood pressure, which remained between 80-130 mmHg during the whole scan time. Importantly, when motion artifacts occurred (example 1), they became apparent in both the blood pressure and the fMRI time course.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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