Do electrode properties create a problem in interpreting local field potential recordings?

Local field potential (LFP) recordings within the brain have become an important tool used by neuroscientists to make inferences about the activity of a population of cells near an electrode. Each passing year analysis of LFPs in neuroscience seems to bring important new insights on the possible workings of networks in the brain to produce behavior (Buschman and Miller 2007; Canolty et al. 2006; Gregoriou et al. 2009; Liu and Newsome 2006; Lubenov and Siapas 2009; Pesaran et al. 2008; Womelsdorf et al. 2006). Indeed LFPs have become a near-ubiquitous tool in neurophysiology seemingly in use anywhere extracellular spikes are also recorded. One issue that often comes up among those who interpret LFP data is the uncertainty about how electrode impedance and other electrode parameters affect LFP recordings, presenting a potential problem in their interpretation. Indeed this is a complex question, given that current flow in the brain depends on a multitude of factors and extracellular recordings cannot uncover the precise neural events giving rise to a specific LFP voltage. Amidst this uncertainty, one commonly mentioned idea that exists today is the notion that microelectrodes of different impedances or geometries might integrate signals across space differently which could lead to differing results between experiments that use electrodes of different impedances to collect LFP data. This notion has been frequently expressed verbally by many, though direct discussions of it in the literature (Pesaran 2009) have been more rare. However, literature discussing how these electrode parameters affect spike recordings (Andersen et al. 2010; Moxon 1999; Paik et al. 2003; Ward et al. 2009) is more commonly found. Despite the relative prevalence of this question in the field, research investigating it has been lacking and no definitive answer has yet been proposed. However, we believe that the answer to this question can be found from information gleaned from a range of existing literature and published data, although most in the field are not presently aware of this. The uncertainty surrounding this issue is important to address because it creates a potential barrier for the comparison of LFP data across experiments and laboratories. Furthermore, as the interpretation of LFPs continues to move beyond its infancy further into the territory of a standard neuroscience technique, such comparisons will be increasingly common and important for building consensuses in the field. As we describe here, we believe this issue presents one of the rare cases in neuroscience in which the answer that would make the work of trying to understand the brain easier also happens to be true. That is to say, provided that the proper recording equipment is used, the impedance and geometry of microelectrode recording sites in the ranges typically used in extracellular experiments do not appreciably affect LFP recordings. Scientists in fact do not need to attend to this issue when interpreting LFP data or when comparing such results across experiments and laboratories. To defend this claim, the first point to clarify a priori is that an electrode can be considered to report the average voltage present at its uninsulated tip or recording site (Nunez and Srinivasan 2006; Robinson 1968). Indeed by using metal microelectrodes suspended in saline, we have verified that this was the case and that this model presented years ago by David Robinson does hold true (Nelson et al. 2008). Thus the only sense in which an electrode integrates a signal across space is by determining this average voltage. The shape and size of an electrode’s recording site will not, for example, affect the way in which it responds to distant as opposed to nearby voltage sources. Second, if the proper recording equipment is used, the voltage that is ultimately amplified and recorded will not be appreciably electrically affected by the electrode’s impedance. Indeed in previous work we demonstrated this to be the case (Nelson et al. 2008). Recorded voltages in saline using electrode impedances spanning the range typically used in extracellular experiments were independent of the electrode’s impedance when using a headstage with a high ( 1 G ) input impedance. This does require some attention from neurophysiologists though. For example another commercially available headstage we tested had a lower input impedance that led to electrode impedance–dependent signal distortions. Fortunately, when they occur these distortions can be corrected post hoc (Nelson et al. 2008), as reported in several recent publications (Gregoriou et al. 2009; Siegel et al. 2009). A separate question from whether the impedance of an electrode electrically influences the recorded voltage is the question of whether the size and geometry of the recording site have an impact on the recorded LFPs. Within the framework that we have described here, one can conceive how during a recording these parameters could affect the average voltage present over the whole uninsulated site and thus affect the recorded values. An electrode’s impedance is of course highly dependent on the size of its uninsulated surface area. Indeed impedance, which is more easily measured, is essentially used only as a proxy to describe an electrode’s uninsulated surface area, which is of more interest to neuroscientists. For spike recordings, for example, the general viewpoints in the field tend to be that larger recording sites spanning more of the extracellular Address for reprint requests and other correspondence: M. Nelson, CRICM, UMR S975, INSERM/Université Pierre et Marie Curie, Neurologie et Thérapeutique Expérimentale, Hôpital de la Salpêtrière, 47 boulevard de l’Hôpital, 75651 Paris Cedex 13, France (E-mail: [email protected]). J Neurophysiol 103: 2315–2317, 2010. First published March 10, 2010; doi:10.1152/jn.00157.2010.