Dynamics of cortical neurovascular coupling analyzed by simultaneous DC-magnetoencephalography and time-resolved near-infrared spectroscopy Bruno-Marcel Mackert, a, ⁎ Stefanie Leistner, a Tilmann Sander, b Adam Liebert, b,c Heidrun Wabnitz, b Martin Burghoff, b Lutz Trahms, b Rainer Macdonald, b and Gabriel Curio a a Department of Neurology, Campus Benjamin Franklin, Charite-Universitaetsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany b Physikalisch-Technische Bundesanstalt, Abbestr. 2-12, 10587 Berlin, Germany c Institute of Biocybernetics and Biomedical Engineering, Trojdena 4, 02-109 Warsaw, Poland Received 26 January 2007; revised 21 September 2007; accepted 24 September 2007 Available online 29 September 2007 Functional magnetic resonance imaging (fMRI) visualizes activated brain areas with a high spatial resolution. The activation signal is determined by the local change of cerebral blood oxygenation, blood volume and blood flow which serve as surrogate marker for the neuronal signal itself. Here, the complex coupling between these parameters and the electrophysiologic activity is characterized non- invasively in humans during a simple motor task using simultaneously DC-magnetoencephalography (DC-MEG), for the detection of neuro- nal signals, and time-resolved near-infrared spectroscopy (trNIRS), for cortical metabolic/vascular responses: over the left primary motor cortex hand area of healthy subjects DC-fields and trNIRS parameters followed closely the 30 s motor task cycles, i.e., finger movements of the right hand alternating with rest. In subjects showing a sufficient signal- to-noise ratio the analysis of variance of photon time of flight proved that the task-related trNIRS changes originated from the cortex. While onset and relaxation started simultaneously, trNIRS signals reached 50% of the maximum level 1–4 s later than the DC-MEG-signals. The non-invasive ‘dual’ setup helps to characterize simultaneously the two complementary aspects of the ‘hemodynamic inverse problem’, i.e., the coupling of neuronal and vascular/metabolic signals, in healthy subjects and provides a new analysis perspective for pathophysiological coupling concepts in diverse diseases, e.g., in stroke, hypertension and Alzheimer’s disease. © 2007 Elsevier Inc. All rights reserved. Keywords: Neurovascular coupling; Functional brain mapping; DC- magnetoencephalography (DC-MEG); DC-electroencephalography (DC- EEG); Near-infrared spectroscopy (NIRS); Spreading depression Introduction Modern non-invasive neuroimaging techniques, e.g., BOLD fMRI (blood oxygenation level dependent functional magnetic response imaging; Kwong et al., 1992; Ogawa et al., 1992; Belli- veau et al., 1991), allow us in an unprecedented manner to localize and analyze activation profiles of and the interplay between task- related cortical cell populations in humans in a plenitude of different physiological tasks. Using these techniques the under- standing of the functional cortical organization, the connectivity between different cortical areas and the dynamics of the neuronal information transfer has been greatly broadened. When analyzing the imaging results one has, however, to keep in mind, that the activation marker used in these fMRI studies relies on a surrogate signal, i.e., the change of cerebral hemoglobin oxygenation, and also blood volume and blood flow. For this reason, the BOLD response is not directly and not linearly related to the neuronal signal itself (review: Buckner, 2003; Lauritzen and Gold, 2003; Logothetis and Pfeuffer, 2004; Lauritzen, 2005). Anatomical structures, e.g., lumen and density of cortical vessels, the type of neuronal activity and cells, e.g., excitatory or inhibitory, the basic cerebral blood flow as well as other coupling-related phenomena can influence the signal. Numerous recent invasive studies in animals using combined functional imaging and intracortical electrical recording have highlighted this “hemodynamic inverse problem” (Logothetis et al., 2001; Lauritzen and Gold, 2003; Sheth et al., 2004). In the present study a dual non-invasive approach in humans is used to characterize the multifactorial interplay between the activ- ation dependent blood oxygenation signal and the neuronal signal itself on the time scale of the hemodynamic response, i.e., in the range of seconds. Near-infrared spectroscopy (NIRS), which is a bedside tool to measure non-invasively cortical changes in oxy- and deoxyhemoglobin concentrations in humans, is combined with simultaneous direct-current magnetoencephalography (DC-MEG), www.elsevier.com/locate/ynimg NeuroImage 39 (2008) 979 – 986 ⁎ Corresponding author. Fax: +49 30 8445 4264. E-mail address: bruno-marcel.mackert@charite.de (B.-M. Mackert). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.09.037