Hunting for neuronal currents: absence of rapid MRI signal changes during visual-evoked response

doi:10.1016/j.neuroimage.2004.07.003

NeuroImage

Volume 23, Issue 3, November 2004, Pages 1059-1067

https://doi.org/10.1016/j.neuroimage.2004.07.003 Get rights and content

Abstract

While recent reports have advocated the use of magnetic resonance imaging (MRI) to detect the effects of neuronal currents associated with human brain activity, only preliminary experimental data have been presented so far to demonstrate the feasibility of the method. Furthermore, it has not been adequately demonstrated that (1) MRI can separate neuronal current (NC) effects from other effects such as blood oxygen level-dependent (BOLD) contrast; (2) MRI has adequate sensitivity to detect NCs in vivo. In this work, we introduce a method that can separate slow (e.g., BOLD) processes from potential rapid (e.g., NC) processes and apply this method to investigate whether MRI allows detection of an NC response to a visual stimulus. MRI studies (n = 8) at 3.0 T using a sensitive multichannel detector showed insignificant effects related to NCs (averaged t < 0.05), in the presence of a highly significant BOLD signal (t = 6.15 ± 0.90). In contrast, magnetoencephalography (MEG) experiments performed under similar conditions on the same subjects showed highly significant electrical activity (t = 7.90 ± 2.28). It is concluded that, under the conditions used in this study, the sensitivity of MRI to detect evoked responses through NCs is at least an order of magnitude below that of BOLD-based functional MRI (fMRI) or MEG and too low to be practically useful.

Introduction

Both spatial and temporal resolution of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) are limited by the underlying physiologic processes, including the dilation of the arteriolar vasculature through neurovascular coupling (Zonta et al., 2003), the ensuing flow response (Kwong et al., 1992), and the hemoglobin transit through the capillary bed and macrovasculature (Duyn et al., 1994, Lee et al., 1995, Mandeville and Marota, 1999). The temporal resolution of fMRI and maybe also its spatial resolution could be substantially improved if MRI can be sensitized to detect the changes in electrical activity associated with brain activation. Changes in both microscopic (e.g., neuronal spiking) and macroscopic electrical activity (e.g., local field potentials) occur on time scales well below the BOLD time scale of several seconds and contain potentially important information, complementary to that available through the BOLD-based signals. On the other hand, established techniques that measure electrical brain activity through intracranial electrodes, voltage sensitive dyes (Shoham and Grinvald, 2001), or electroencephalography (EEG) and magnetoencephalography (MEG) are either invasive or have poor spatial resolution.

Recently, a number of researchers have suggested the use of fMRI to detect changes in neuronal currents (NCs) during human brain activation (Bodurka and Bandettini, 2002, Kamei et al., 1999, Konn et al., 2003, Xiong et al., 2003). One of the claims is that NC-based MRI has the ability to detect visual and sensorimotor activation with a sensitivity similar to that of BOLD fMRI (Xiong et al., 2003). However, as of yet, this claim has not been validated. Furthermore, previously proposed methodology (Xiong et al., 2003) has a relatively poor efficiency at detecting NCs and does not optimally separate NC contrast from BOLD contrast.

The purpose of the current work was to design an fMRI method that is highly sensitive to both the rapid and slow effects associated with NC and BOLD contrast, respectively, while at the same time allowing for excellent separation of the two effects. Furthermore, the new method was used to quantify the relative sensitivities of NC and BOLD contrast in fMRI experiments of the human visual system and to compare these with the sensitivity of MEG.

Section snippets

Experimental design

The fMRI method was designed to measure BOLD effects and potential NC effects simultaneously, separably, and with high sensitivity. MRI contrast to NCs was envisioned to originate from the effects of intracellular dendritic currents on the MRI signal, including signal amplitude (magnitude) reduction due to intravoxel dephasing (Xiong et al., 2003) and possibly signal phase effects (Kamei et al., 1999). To optimally capture these signal changes, single shot gradient echo EPI was performed with

Image quality

The raw EPI–MRI images were somewhat affected by signal dropout due to intravoxel dephasing, as expected under the conditions of long TE (81 ms), high magnetic field (3.0 T) and large voxel size. However, image quality was reasonable in occipital areas, partly because of the manual shim optimization before scanning. In all subjects, the SNR exceeded 30:1 in the visual cortex, and the TSD averaged 2.87% (Table 1). The TSD of the average signal in the activated pixels (TSD–ROI) was 0.49%, which

General remarks

A novel technique was developed that allows separation of fast and slow signals in response to neuronal activation. The technique was combined with a sensitive MRI scan technique to investigate the feasibility to detect evoked electrical activity in the human visual system. In contrast with previous reports (Kamei et al., 1999, Xiong et al., 2003), evoked NCs did not lead to significant rapid signal changes in MRI, while slow (BOLD) signal changes were highly significant. Furthermore, in

Acknowledgments

Jerzy Bodurka, Martijn Jansma, and Alan Koretsky (all at NIH) are acknowledged for helpful and stimulating discussions.

References (26)

G.T. Buracas et al.
Efficient design of event-related fMRI experiments using m-sequences
NeuroImage
(2002)
P. Kellman et al.
Method for functional MRI mapping of nonlinear response
NeuroImage
(2003)
G. Pfurtscheller
Event-related synchronization (ERS): an electrophysiological correlate of cortical areas at rest
Electroencephalogr. Clin. Neurophysiol.
(1992)
E.E. Sutter
Imaging visual function with the multifocal m-sequence technique
Vision Res.
(2001)
J. Bodurka et al.
Toward direct mapping of neuronal activity: MRI detection of ultraweak, transient magnetic field changes
Magn. Reson. Med.
(2002)
J. Bodurka et al.
Scalable multichannel MRI data acquisition system
Magn. Reson. Med.
(2004)
H. Bruder et al.
Image reconstruction for echo planar imaging with nonequidistant k-space sampling
Magn. Reson. Med.
(1992)
J.A. de Zwart et al.
Application of sensitivity-encoded echo-planar imaging for blood oxygen level-dependent functional brain imaging dagger
Magn. Reson. Med.
(2002)
J.A. de Zwart et al.
Signal-to-noise and parallel imaging performance of a 16-channel receive-only brain coil array at 3.0 Tesla
Magn. Reson. Med.
(2004)
J.H. Duyn
Steady state effects in fast gradient echo magnetic resonance imaging
Magn. Reson. Med.
(1997)

J.H. Duyn et al.

Inflow versus deoxyhemoglobin effects in BOLD functional MRI using gradient echoes at 1.5 T

NMR Biomed.

(1994)

F. Fera et al.

EPI–BOLD fMRI of human motor cortex at 1.5 T and 3.0 T: sensitivity dependence on echo time and acquisition bandwidth

J. Magn. Reson. Imaging

(2004)

J.C. Horton et al.

The representation of the visual field in human striate cortex. A revision of the classic Holmes map

Arch. Ophthalmol.

(1991)

Cited by (68)

Detection of tiny oscillatory magnetic fields using low-field MRI: A combined phantom and simulation study
2020, Journal of Magnetic Resonance
We demonstrated the feasibility of the spin-lock preparation sequence using low-field magnetic resonance (MR) imaging that prevents interference from blood-oxygenation-level-dependent effects. We focused on two spin-lock preparations: spin-lock Mz (SL-Mz) and stimulus-induced rotary saturation (SIRS) and analyzed the magnetization dynamics during the sequences using the Bloch equation. Next, we performed phantom experiments using a loop coil to investigate the MR signal change as a function of the target signal strength and phase. Furthermore, we performed curve fittings to consider the radio frequency, which agreed with the experimental results. Then, we investigated the detectable strength of the magnetic field, and the SL-Mz detected a signal strength of 2.34 nT. In conclusion, our experimental results showed good agreement with the results obtained using the Bloch equation.
Direct neural current imaging in an intact cerebellum with magnetic resonance imaging
2016, NeuroImage
The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR = 100 ms) at 4.7 T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1 mm³, (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27–0.37°, corresponding to local magnetic field changes of 0.67–0.93 nT (for TE = 26 ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents.
A comprehensive study of sensitivity in measuring oscillatory magnetic fields using rotary saturation pulse sequences
2016, Magnetic Resonance Imaging
Detecting the oscillatory currents with a specific frequency distribution may have the potential to make neuronal current MRI (ncMRI) come true. The phase shift or dephasing induced by both positive and negative episodes of oscillatory neuronal currents is likely to be canceled out over the echo time in typical BOLD-contrast fMRI experiments. Based on the contrast of rotary saturation, both of the recently developed spin-locked oscillatory excitation (SLOE) and stimulus-induced rotary saturation (SIRS) pulse sequences have been demonstrated to be able to detect weak oscillatory magnetic fields in phantoms with 3 T MR scanners. In this report, through Bloch equation simulation as well as water phantom and anesthetic rats experiments, we comprehensively evaluate and compare the sensitivities of these two methods (SLOE and SIRS) in detecting the oscillatory magnetic fields for both high (100 Hz) and low (10 Hz) oscillation frequencies, while using their respective optimal imaging parameters. In agreement with the theoretical predications, both the simulated and experimental results showed that the SLOE method features a much higher detection sensitivity of weak magnetic fields than that of the SIRS method. SLOE was able to detect applied oscillatory magnetic fields as low as 0.1 nT in a water phantom and 0.5 nT in rat brains and the deteriorated noise levels in rat data may account for the reduced sensitivity in vivo. These promising results form the foundation for direct detection of in vivo neuronal currents using MRI.
Evolution of Instrumentation for Functional Magnetic Resonance Imaging
2015, Brain Mapping: An Encyclopedic Reference
Since the discovery of functional MRI (fMRI) early in the 1990s, major developments in MRI instrumentation have provided particular benefits for human fMRI. Improvements in system stability and signal detection hardware, as well as an increase in magnetic field strength and rises in the amplitude and switching speed of gradients, have significantly increased fMRI spatial resolution and contrast-to-noise ratio. These technological improvements and their specific impact on fMRI research are reviewed here.
MRI and fMRI Optimizations and Applications
2015, Brain Mapping: An Encyclopedic Reference
MRI signal phase oscillates with neuronal activity in cerebral cortex: Implications for neuronal current imaging
2014, NeuroImage
Neuronal activity produces transient ionic currents that may be detectable using magnetic resonance imaging (MRI). We examined the feasibility of MRI-based detection of neuronal currents using computer simulations based on the laminar cortex model (LCM). Instead of simulating the activity of single neurons, we decomposed neuronal activity to action potentials (AP) and postsynaptic potentials (PSP). The geometries of dendrites and axons were generated dynamically to account for diverse neuronal morphologies. Magnetic fields associated with APs and PSPs were calculated during spontaneous and stimulated cortical activity, from which the neuronal current induced MRI signal was determined. We found that the MRI signal magnitude change (< 0.1 ppm) is below currently detectable levels but that the signal phase change is likely to be detectable. Furthermore, neuronal MRI signals are sensitive to temporal and spatial variations in neuronal activity but independent of the intensity of neuronal activation. Synchronised neuronal activity produces large phase changes (in the order of 0.1 mrad). However, signal phase oscillates with neuronal activity. Consequently, MRI scans need to be synchronised with neuronal oscillations to maximise the likelihood of detecting signal phase changes due to neuronal currents. These findings inform the design of MRI experiments to detect neuronal currents.

View all citing articles on Scopus

View full text

Published by Elsevier Inc.

Hunting for neuronal currents: absence of rapid MRI signal changes during visual-evoked response

Abstract

Introduction

Section snippets

Experimental design

Image quality

General remarks

Acknowledgments

NeuroImage

NeuroImage

Electroencephalogr. Clin. Neurophysiol.

Vision Res.

Toward direct mapping of neuronal activity: MRI detection of ultraweak, transient magnetic field changes

Magn. Reson. Med.

Scalable multichannel MRI data acquisition system

Magn. Reson. Med.

Image reconstruction for echo planar imaging with nonequidistant k-space sampling

Magn. Reson. Med.

Application of sensitivity-encoded echo-planar imaging for blood oxygen level-dependent functional brain imaging dagger

Magn. Reson. Med.

Signal-to-noise and parallel imaging performance of a 16-channel receive-only brain coil array at 3.0 Tesla

Magn. Reson. Med.

Steady state effects in fast gradient echo magnetic resonance imaging

Magn. Reson. Med.

Inflow versus deoxyhemoglobin effects in BOLD functional MRI using gradient echoes at 1.5 T

NMR Biomed.

EPI–BOLD fMRI of human motor cortex at 1.5 T and 3.0 T: sensitivity dependence on echo time and acquisition bandwidth

J. Magn. Reson. Imaging

The representation of the visual field in human striate cortex. A revision of the classic Holmes map

Arch. Ophthalmol.