Ahalya Viswanathan

Concurrent measurements of PO₂, neural activity, and BOLD in macaque cortex

Ahalya Viswanathan

Introduction and Scientific Aims

Elucidating the relationship between oxygen metabolism (CMRO₂), BOLD, and neural activity is essential to our understanding of neurovascular coupling [1].  Recent studies used MR measurements to estimate CMRO₂ [2]. 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 [3]. Manipulation of visual stimuli yields specific changes in PO₂ dip and peak amplitude, allowing us to examine neurovascular coupling at sub-millimeter resolution [4].  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.

Methods

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

Ulrich Schridde

References

1. Logothetis, N.K. What we can and cannot do with fMRI. Nature 453, 869-78 (2008).

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 Captions

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.