Initial attempts at directly detecting alpha wave activity in the brain using MRI Daniel Konn, Sean Leach, Penny Gowland, Richard Bowtell * Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, NG7 2RD, UK Received 8 October 2004; accepted 8 October 2004 Abstract The bdirect detectionQ of neuronal activity by MRI could offer improved spatial and temporal resolution compared to the blood oxygenation level-dependent (BOLD) effect. Here we describe initial attempts to use MRI to detect directly the neuronal currents resulting from spontaneous alpha wave activity, which have previously been shown to generate the largest extracranial magnetic fields. Experiments were successfully carried out on four subjects at 3 T. A single slice was imaged at a rate of 25 images per second under two conditions. The first (in darkness with eyes-closed) was chosen to promote alpha wave activity, while the second (eyes-open viewing a visual stimulus) was chosen to suppress it. The fluctuations of the phase and magnitude of the resulting MR image data were frequency analysed, and tested for the signature of both alpha wave activity and neuronal activity evoked by the visual stimulus. Regions were found that consistently showed elevated power in fluctuations of the phase of the MR signal, in the frequency range of alpha waves, during the eyes-closed condition. It was conservatively assumed that if oscillations occurred at the same frequency in the magnitude signal from the same region or at the same frequency in the phase or magnitude signal from other regions overlying large vessels or cerebrospinal fluid (CSF), then the phase changes were not due to neuronal activity related to alpha waves. Using these criteria the data obtained were consistent with direct detection of alpha wave activity in three of the four volunteers. No significant MR signal fluctuations due to evoked activity were identified. D 2004 Elsevier Inc. All rights reserved. Keywords: Direct detection; Brain rhythm; Magnetic resonance imaging; fMRI; Neuronal activity 1. Introduction The blood oxygenation level-dependent (BOLD) fMRI signal is an indirect measure of neuronal activation mediated by the haemodynamic response. Electroencephalography (EEG) and magnetoencephalography (MEG) provide meth- ods of more directly monitoring the electrical activity of neurons. In the case of MEG, it is the small magnetic fields generated by neuronal current flow that are detected. Magnetic resonance imaging can, in principle, also be used to detect these neuromagnetic fields via their effect on the phase or magnitude of the MR signal [1–3]. This approach, which is now becoming known as bdirect detectionQ of neuronal activity by MRI, potentially offers improved spatial and temporal resolution compared to the BOLD effect [1,3]. Previously described simulations of the fields generated by neuronal currents, modelled as uniform, extended dipoles, have suggested that direct detection of neuronal activity is best accomplished by monitoring the phase rather than the magnitude of the MR signal. These simulations indicated that the contrast-to-noise (CNR) of phase variations evoked by typical neuromagnetic fields are more than two orders of magnitude higher than those of variations in signal magnitude, and that at 3 T it should be possible to detect the phase change resulting from a dipole of 8 nAm strength and 662 mm 3 spatial extent [4]. The recent publication of data showing changes in signal magnitude of about 1% that are apparently due to evoked neuronal currents [2] has fuelled some debate over whether phase or magnitude changes offer the optimal route to detection of neuronal currents via MRI. Further simulations, which are briefly detailed in this paper, indicate that the local magnetic field variations generated by typical post- synaptic potentials are too small to cause significant changes in signal magnitude. Consequently, the data analysis described in this paper is based on the assumption that the 0730-725X/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.mri.2004.10.012 * Corresponding author. Tel.: +44 115 9514737; fax: +44 115 9515166. E-mail address: richard.bowtell@nottingham.ac.uk (R. Bowtell). Magnetic Resonance Imaging 22 (2004) 1413 – 1427