An fMRI study of neural interaction in large-scale cortico-thalamic visual network

Abstract

To date there is still no proper neuroimaging methods suitable for noninvasively providing both detailed spatial and temporal information of neural interaction across large-scale brain networks. This limitation has impeded the advance of neuroscience research. In an attempt to overcome this challenge, Ogawa et al. applied a paired-stimulus paradigm, which is composed of a pair of stimuli separated by a variable inter-stimulus interval (ISI), to decode temporal information of neural interaction from amplitude modulation of the blood-oxygenation-level-dependent (BOLD) responses elicited by the neural interaction pursued [Ogawa, S., Lee, T.-M., Stepnoski, R., Chen, W., Zhu, X.H., Ugurbil, K., 2000. An approach to probe neural systems interaction by functional MRI at neural time scale down to milliseconds. Proc. Natl. Acad Sci. U S A 97, 11026-11031.]. Although application of this paradigm has been demonstrated in a few publications, most of them only focused on investigating cortico-cortical interaction. Considering the vital roles that cortico-thalamic networks play in brain communication and function, extending the applicability of this method to studying cortico-thalamic neural interaction should be significant. In this study, we applied the paired-visual-stimulus paradigm to simultaneously measure the BOLD amplitude modulations as a function of ISI in the lateral geniculate nucleus (LGN) and primary visual cortex (V1) in the cat brain. The results reveal that both V1 and LGN BOLD responses were significantly suppressed when the visual system was within the refractory period at ISI<or=1 s and the suppression extent was gradually recovered when ISI became longer. Both BOLD and electrophysiological measurements show a facilitatory activity in V1 at ISI approximately 1.5 s, but not in LGN. Furthermore, there was additional and consistent reduction in the LGN BOLD response compared to V1 within the range of ISI below 4 s, which is likely controlled by inhibitory effects through the cortico-geniculate feedback. These findings together suggest that the dynamic fMRI approach applied in this study is sensitive to neuronal inhibitory and facilitatory interactions and it should be useful for noninvasively investigating large-scale cortico-thalamic neural networks.

Figure 1

(a) Activation maps generated using the time shifted cross-correlation method in the task with ISI=1000 ms in one cat. The threshold is chosen at p < 0.01. (b) Common activation map generated based on the following criterion: a pixel is deemed as activated in the common activation map only if it passes the threshold for at least half of all the tasks: i.e., this pixel is considered activated in at least eight of all the tasks. This common activation map composed of all activated pixels in LGN and areas 17 and 18 (i.e., V1) created based on this criterion is used for quantifying BOLD amplitudes for all the tasks.

Figure 2

Averaged BOLD time courses of all tasks from the ROI of (a) LGN and (b) V1. The tasks include a single stimulus task and paired-stimulus tasks with varied ISIs.

Figure 2

Averaged BOLD time courses of all tasks from the ROI of (a) LGN and (b) V1. The tasks include a single stimulus task and paired-stimulus tasks with varied ISIs.

Figure 3

(a) The averaged time courses of BOLD responses to the first (the leftmost one) and second stimulus at each ISI in LGN. BOLD response to the second stimulus at a paired-stimulus condition is individuated by subtracting the BOLD time course at the single-stimulus conditions from that at the paired-stimulus condition. (b) The averaged time courses of BOLD responses to the first (the leftmost one) and second stimulus at each ISI in V1.

Figure 4

Normalized BOLD integral as a function of ISI in LGN and V1. At both ROIs, BOLD responses are significantly suppressed (i.e., below the reference line) at ISIs of < 1 second. When ISI gets longer, BOLD suppression at both ROIs gradually becomes smaller. Suppression in V1 BOLD activity completely disappears when ISI ≥ 1 second, whereas BOLD suppression in LGN sustains for even longer ISIs. V1 activity also shows a short period (~ 1 s) of facilitation (i.e., above the reference line) after ISI > 1 second.

Figure 5

VEP signals detected from one representative cat visual cortex at (a) ISI = 100 ms and (b) ISI = 3000 ms, respectively.

Figure 6

Normalized VEP amplitudes in V1 as a function of ISI, showing a similar temporal behavior as BOLD activity. The presented VEP amplitudes were averaged from six measurements; and if they are > 2 indicating neuronal facilitation (i.e., above the reference line) and if < 2 indicating neuronal inhibition (below the reference line).

Figure 7

Correlation between the normalized VEP and normalized BOLD amplitudes measured under varied ISIs (R² = 0.91).

Figure 8

Averaged BOLD time course in response to the paired-flash stimulation at ISI = 20 s.