Oxygen Level and LFP in Task-Positive and Task-Negative Areas: Bridging BOLD fMRI and Electrophysiology

Abstract

The human default mode network (DMN) shows decreased blood oxygen level dependent (BOLD) signals in response to a wide range of attention-demanding tasks. Our understanding of the specifics regarding the neural activity underlying these "task-negative" BOLD responses remains incomplete. We paired oxygen polarography, an electrode-based oxygen measurement technique, with standard electrophysiological recording to assess the relationship of oxygen and neural activity in task-negative posterior cingulate cortex (PCC), a hub of the DMN, and visually responsive task-positive area V3 in the awake macaque. In response to engaging visual stimulation, oxygen, LFP power, and multi-unit activity in PCC showed transient activation followed by sustained suppression. In V3, oxygen, LFP power, and multi-unit activity showed an initial phasic response to the stimulus followed by sustained activation. Oxygen responses were correlated with LFP power in both areas, although the apparent hemodynamic coupling between oxygen level and electrophysiology differed across areas. Our results suggest that oxygen responses reflect changes in LFP power and multi-unit activity and that either the coupling of neural activity to blood flow and metabolism differs between PCC and V3 or computing a linear transformation from a single LFP band to oxygen level does not capture the true physiological process.

Keywords: default mode network; neurohemodynamic coupling; oxygen polarography; power spectrum; transfer function.

Figure 1.

Percent oxygen modulation (mean ± SEM) relative to the period 0–5 s before stimulus onset. Yellow-black bars mark the 15-s, 1-Hz stroboscopic stimulus. Both areas show a 2.3-s delay followed by an increase in oxygen, peaking at 3.7 s in PCC and 6.2 s in V3. This is followed by a sustained positive response in V3 and a sustained negative response in PCC. After the stimulus is turned off, there is a late suppression in both areas followed by a return to baseline at ∼15 s after the end of stimulation. Data from 1025 and 942 trials are included in the PCC and V3 traces, respectively.

Figure 2.

(a) LFP power modulation relative to baseline (0–5 s before stimulus onset) in standard error units (SEM is estimated based on baseline activity). Arrows indicate stimulus onset and offset. Data from 607 and 605 trials are included for V3 (left) and PCC (right), respectively. (b) LFP power modulation (mean ± SEM) as a function of frequency (log) during stimulation for V3 and PCC.

Figure 3.

Percent modulation of LFP power for standard EEG bands. V3 shows complex phasic responses riding on top of tonic increases (gamma and delta) and decreases (alpha and theta) in power relative to baseline. PCC shows smaller phasic responses and tonic decreases.

Figure 4.

Flash-triggered average of LFP power for fourth to fifteen flashes. V3 shows prominent transients at the onset of each flash, with additional structure just before and after flash offset. Surprisingly, PCC also shows single-flash responses. The initial transients to the first flash (which are not included in this average; nor the second nor third flashes) are comparable in size with the V3 transients, but the later responses are ∼10 times smaller.

Figure 5.

Hemodynamic coupling in V3 and PCC. First column: gamma-band LFP power in V3 (red) and PCC (blue). Second column: candidate transfer functions used to predict the oxygen response (third column) based on the LFP response (first column). The units of measure are percent oxygen modulation divided by percent LFP power modulation. Third column: predicted and actual oxygen responses. The predicted response is the convolution of the neural response (first column) with the selected transfer function (second column). Shading highlights any mismatch between the predicted and actual oxygen responses. Rows 1 + 2: A single parameter canonical HRF (canonical HRF; see text), fit to either the V3 (orange in the second column) or PCC data (cyan in the second column), is much smaller in V3 than PCC. Only 53% of the variance in the V3 oxygen signal can be predicted, and the initial transients are missed in both areas. Note that the scale parameter for the function is 3.5 times larger in PCC than V3 (as seen in the height of the orange versus cyan curves in Column 2). Rows 3 + 4: The best-fitting 8-parameter generic HRFs (see text) do well but have different shapes in the 2 areas. The fit for V3 (orange in the second column) has much smaller amplitude whereas the fit for PCC (cyan in the second column) contains an initial negativity that is not present in V3. Rows 5 + 6: A computed transfer function (see text) does well in both areas but, like the 8-parameter fits, is smaller in V3 (orange in the second column) and contains an initial negativity only in PCC (cyan in the second column).

Figure 6.

(a) A linear correlation (mean ± SEM) between oxygen and LFP responses at each frequency. Correlations were computed at lags from −5 to +12 s, and the highest correlation at each frequency is shown. (b) The amplitude (mean ± SEM) of the main lobe of generic HRFs in V3 and PCC at each of 6 frequency bands. Generic HRF was calculated for each data session, and the main lobe was defined as the lobe with the larger deviation from baseline. For all 6 bands, the amplitude of the main lobe of generic HRFs are significantly different in the 2 areas.