Devor A, Ulbert I, Dunn AK, Narayanan SN, Joness SR, Mark L, Andermann DAB, Dale AMCoupling of the cortical hemodynamic response to cortical and thalamic neuronal activity. Proc Natl Acad Sci USA 102:3822-3827

Massachusetts General Hospital NMR Center and Program in Biophysics, Harvard Medical School, Charlestown, MA 02129, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2005; 102(10):3822-7. DOI: 10.1073/pnas.0407789102
Source: PubMed
Accurate interpretation of functional MRI (fMRI) signals requires knowledge of the relationship between the hemodynamic response and the neuronal activity that underlies it. Here we address the question of coupling between pre- and postsynaptic neuronal activity and the hemodynamic response in rodent somatosensory (Barrel) cortex in response to single-whisker deflection. Using full-field multiwavelength optical imaging of hemoglobin oxygenation and electrophysiological recordings of spiking activity and local field potentials, we demonstrate that a point hemodynamic measure is influenced by neuronal activity across multiple cortical columns. We demonstrate that the hemodynamic response is a spatiotemporal convolution of the neuronal activation. Therefore, positive hemodynamic response in one cortical column might be explained by neuronal activity not only in that column but also in the neighboring columns. Thus, attempts at characterizing the neurovascular relationship based on point measurements of electrophysiology and hemodynamics may yield inconsistent results, depending on the spatial extent of neuronal activation. The finding that the hemodynamic signal observed at a given location is a function of electrophysiological activity over a broad spatial region helps explain a previously observed increase of local vascular response beyond the saturation of local neuronal activity. We also demonstrate that the oxy- and total-hemoglobin hemodynamic responses can be well approximated by space-time separable functions with an antagonistic center-surround spatial pattern extending over several millimeters. The surround "negative" hemodynamic activity did not correspond to observable changes in neuronal activity. The complex spatial integration of the hemodynamic response should be considered when interpreting fMRI data.

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    • "In experimental animal models, it is possible to combine neuronal recordings with simultaneous measurement of haemodynamics in order to better characterise the source of the negative BOLD signal and investigate in fine detail the coupling between neuronal and haemodynamic signal changes (Boorman et al., 2010). Evidence suggests negative BOLD signals can have separable haemodynamic (Devor et al., 2005; Harel et al., 2002) and neuronal (Shmuel et al., 2006) sources and may occur in the presence of increased neuronal signalling (Angenstein et al., 2009). Furthermore, in cases where negative BOLD signals are associated with reduced "
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    • "The point spread function (PSF) in BOLD fMRI is ultimately limited by the spatial specificity of neurovascular coupling mechanisms (Devor et al., 2005; Hillman et al., 2007; Kim et al., 2004; Menon and Kim, 1999; Sirotin et al., 2009). Further reducing the accuracy of signal localization are the downstream BOLD effects in the venous architecture . "
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    • "Berwick et al., 2008; Devor et al., 2005; Harris et al., 2013; Huttunen et al., 2008; Kennerley et al., 2011) and resting-state fluctuations (Bruyns‐Haylett et al., 2013). It has also been shown that neither the spatial–temporal pattern of the evoked hemodynamic response (Devor et al., 2005), nor the relationship between neural activity and BOLD fMRI responses (Huttunen et al., 2008), differs between urethane and alpha-chloralose, another anesthetic routinely used in fMRI studies and whose neurovascular coupling characteristics in turn are comparable to a number of other agents (Franceschini et al., 2010). A homoeothermic blanket (Harvard Apparatus) and rectal probe were used to maintain core body temperature at 37 °C. "
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