Concurrent measurements of PO2, neural activity, and BOLD in macaque cortex
Introduction and Scientific Aims
Elucidating the relationship between oxygen metabolism (CMRO2), BOLD, and neural activity is essential to our understanding of neurovascular coupling . Recent studies used MR measurements to estimate CMRO2 . However, limitations include poor spatial resolution and values based on mathematical models. We propose using multi-function electrodes to make direct, simultaneous measurements of tissue oxygen (PO2), BOLD, and neural activity.
PO2 responses are typically biphasic, consisting of an initial negative dip, commonly associated with increases in CMRO2, and a delayed positive peak, thought to reflect increases in cerebral blood flow . Manipulation of visual stimuli yields specific changes in PO2 dip and peak amplitude, allowing us to examine neurovascular coupling at sub-millimeter resolution . We will examine the relative contributions of the PO2 dip and peak to BOLD signal amplitude. We will then quantify the relationship between these signals and the underlying neural activity.
We designed MR-compatible multi-function electrodes that support co-localized measurements of BOLD, PO2, and neural activity. To our knowledge, these are the first electrodes to measure PO2 and neural activity at the same point on the electrode shaft. Anesthetized macaques were placed in a vertical 4.7T scanner and presented polar checkerboard visual stimuli. BOLD, PO2, and neural responses were recorded in primary visual cortex (V1).
Results and Preliminary Conclusions
Representative responses from an experimental session are shown in Figure 1. As expected, following stimulus onset, there is a marked increase in neural activity, followed by increases in PO2 and BOLD.
We have successfully developed multi-function electrodes that simultaneously measure BOLD, PO2, and neural activity in macaque cortex. This new technology promises to help clarify several important questions within neurovascular coupling.
Supervised Students and Collaborators
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2. Leontiev, O. & Buxton, R.B. Reproducibility of BOLD perfusion, and CMRO2 measurements with calibrated BOLD-fMRI. Neuroimage 35, 175-84 (2007).
3. Thompson, J.K., Peterson, M.R. & Freeman, R.D. Separate spatial scales determine neural activity-dependent changes in tissue oxygen within central visual pathways. J Neurosci 25, 9046-58 (2005).
4. Viswanathan, A. & Freeman, R.D. Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity. Nat Neurosci 10, 308-12 (2007).
Figure 1. Concurrent recordings of BOLD, PO2, and gamma LFP responses to a binocularly-presented, fullfield checkerboard stimulus. Signals were measured in primary visual cortex (V1) of an anesthetized adult macaque and are shown averaged across trials (N = 56) in standard deviation units (s.d.u.) relative to the 10 s pre-stimulus baseline. Stimulus onset and duration (8s, gray shaded region) and standard error (dotted lines) are also shown. The inset (top right) depicts the BOLD response, zoomed-in over a smaller range of s.d.u.