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.

14 Reads
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N = 6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data. Copyright © 2015. Published by Elsevier Ltd.
    Neuropharmacology 07/2015; 99. DOI:10.1016/j.neuropharm.2015.07.018 · 5.11 Impact Factor
  • Source
    • "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 . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Resting-state functional MRI (RS-fMRI) is a widely used method for inferring connectivity between brain regions or nodes. As with task-based fMRI, the spatial specificity of the connectivity maps can be distorted by the strong biasing effect of the BOLD signal in macroscopic veins. In RS-fMRI this effect is exacerbated by the temporal coherences of physiological origin between large veins that are widely distributed in the brain. In gradient echo based EPI, used for the vast majority of RS-fMRI, macroscopic veins that carry BOLD-related changes exhibit a strong phase response. This allows for post-processing identification and removal of venous signals using a phase regressor technique. Here, we employ this approach to suppress macrovascular venous contributions in high-field whole-brain RS-fMRI data sets, resulting in significant changes to both the spatial localization of the networks and the correlations between the network nodes. These effects were observed at both the individual and group analysis level, suggesting that venous contamination is a confounding factor for RS-fMRI studies even at relatively low image resolutions. Suppression of the macrovascular signal using the phase regression approach may therefore help to better identify, delineate, and interpret the true structure of large-scale brain networks.
    NeuroImage 06/2014; 100. DOI:10.1016/j.neuroimage.2014.05.079 · 6.36 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue.
    NeuroImage 04/2014; 97(100). DOI:10.1016/j.neuroimage.2014.04.014 · 6.36 Impact Factor
Show more

Preview (2 Sources)

14 Reads
Available from