ARTICLE IN PRESS - University of Oxfordjesper/papers/readgroup...magnetic field generated by neurons using for the first time realistic simulations of neuronal activity and to evaluate

Realistic simulations of neuronal activity: A contribution to the debate on direct detection of neuronal currents by MRI A.M. Cassarà, a, ⁎ G.E. Hagberg, b M. Bianciardi, b M. Migliore, c and B. Maraviglia a,b,d a Dip. di Fisica, Gruppo G1, Università di Roma “La Sapienza”, Piazzale Aldo Moro, 5, 00185, Rome, Italy b Laboratorio di Neuroimmagini, Fondazione Santa Lucia, I.R.C.C.S., 00179 Rome, Italy c Istituto di Biofisica, CNR, Palermo, Italy d Museo Storico della fisica e centro di studi e ricerche “Enrico Fermi”, 00184, Rome, Italy Received 17 January 2007; revised 4 August 2007; accepted 22 August 2007 Many efforts have been done in order to preview the properties of the magnetic resonance (MR) signals produced by the neuronal currents using simulations. In this paper, starting with a detailed calculation of the magnetic field produced by the neuronal currents propagating over single hippocampal CA1 pyramidal neurons placed inside a cubic MR voxel of length 1.2 mm, we proceeded on the estimation of the phase and magnitude MR signals. We then extended the results to layers of parallel and synchronous similar neurons and to ensembles of layers, considering different echo times, voxel volumes and neuronal densities. The descriptions of the neurons and of their electrical activity took into account the real neuronal morphologies and the physiology of the neuronal events. Our results concern: (a) the expected time course of the MR signals produced by the neuronal currents in the brain, based on physiological and anatomical properties; (b) the different contributions of post- synaptic potentials and of action potentials to the MR signals; (c) the estimation of the equivalent current dipole and the influence of its orientation with respect to the external magnetic field on the observable MR signal variations; (d) the size of the estimated neuronal current induced phase and magnitude MR signal changes with respect to the echo time, voxel-size and neuronal density. The inclusion of realistic neuronal properties into the simulation introduces new information that can be helpful for the design of MR sequences for the direct detection of neuronal current effects and the testing of bio-electromagnetic models. © 2007 Elsevier Inc. All rights reserved. Keywords: Pyramidal cells; Hippocampus; Magnetic field changes; Neuronal current MRI Introduction The feasibility to detect the magnetic fields generated by neuronal currents by means of magnetic resonance imaging (nc-MRI) is still a matter of debate (Bandettini et al., 2005; Hagberg et al., 2006). Several works have shown experimental results obtained on phantoms, cell cultures, and by theoretical cal- culations (Kamei et al., 1999; Bodurka et al., 1999, ; Konn et al., 2003, 2004; Bianciardi et al., 2004a; Petridou et al., 2006; Park et al., 2006; Parkes et al., 2007) in favor of the detection of functional MR signal changes induced by the direct effects of neuronal currents. The use of nc-MRI in vivo has yielded, instead, controversial results regarding the feasibility of the technique for the study of brain function in humans (Xiong et al., 2003; Konn et al., 2004; Bianciardi et al., 2004b; Chu et al., 2004; Chow et al., 2006) and neuronal currents in epileptic patients (Liston et al., 2004): in other words, a clear demonstration of neuronal current detection by MRI is still lacking. The disadvantages of currently employed experimental neuronal current MRI approaches have been reviewed in the work of Xue et al. (2006) with emphasis on the direct mapping of neuronal activity in magnitude images performed by the same group (Xiong et al., 2003). Other detailed chronologies of previous works about direct detection of neuronal activity by nc-MRI can be found in Bandettini et al. (2005) and Hagberg et al. (2006). The question regarding the feasibility of neuronal current MRI has been answered affirmatively based on theoretical considerations and simulations (Park et al., 2007, Xue et al., 2006; Bodurka and Bandettini, 2002; Konn et al., 2003) where neurons have been primarily modeled as current dipoles of finite spatial extent. Nevertheless, in previous nc-MRI modeling studies, the effect of the spread of realistic currents was not con- sidered because neither the electrotonic properties of the neurons have been not taken into account nor the complex morphologies of the neuronal tree. The aim of this paper is to present a detailed calculation of the magnetic field generated by neurons using for the first time realistic simulations of neuronal activity and to evaluate the expected signal in phase and magnitude in MRI experiments. The rationale of our work relies on the inclusion of realistic morphologies and biophysical properties of the neurons to describe in a more detailed way the currents flowing in the neuronal trees in a simple neuronal activity (synaptic inputs-spatial integration of excitatory post- model 5 YNIMG-04892; No. of pages: 20; 4C: www.elsevier.com/locate/ynimg NeuroImage xx (2007) xxx – xxx ⁎ Corresponding author. Fax: +39 06 49913484. E-mail address: [email protected] (A.M. Cassarà). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.08.048 ARTICLE IN PRESS Please cite this article as: Cassarà, A.M., et al., Realistic simulations of neuronal activity: A contribution to the debate on direct detection of neuronal currents by MRI, NeuroImage (2007), doi:10.1016/j.neuroimage.2007.08.048

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ARTICLE IN PRESS - University of Oxfordjesper/papers/readgroup...magnetic field generated by neurons using for the first time realistic simulations of neuronal activity and to evaluate