Preserved canonicality of the BOLD hemodynamic response reflects healthy cognition: Insights into the healthy brain through the window of Multiple Sclerosis

Abstract

The hemodynamic response function (HRF), a model of brain blood-flow changes in response to neural activity, reflects communication between neurons and the vasculature that supplies these neurons in part by means of glial cell intermediaries (e.g., astrocytes). Intact neural-vascular communication might play a central role in optimal cognitive performance. This hypothesis can be tested by comparing healthy individuals to those with known white-matter damage and impaired performance, as seen in Multiple Sclerosis (MS). Glial cell intermediaries facilitate the ability of neurons to adequately convey metabolic needs to cerebral vasculature for sufficient oxygen and nutrient perfusion. In this study, we isolated measurements of the HRF that could quantify the extent to which white-matter affects neural-vascular coupling and cognitive performance. HRFs were modeled from multiple brain regions during multiple cognitive tasks using piecewise cubic spline functions, an approach that minimized assumptions regarding HRF shape that may not be valid for diseased populations, and were characterized using two shape metrics (peak amplitude and time-to-peak). Peak amplitude was reduced, and time-to-peak was longer, in MS patients relative to healthy controls. Faster time-to-peak was predicted by faster reaction time, suggesting an important role for vasodilatory speed in the physiology underlying processing speed. These results support the hypothesis that intact neural-glial-vascular communication underlies optimal neural and cognitive functioning.

Figure 1

Canonical hemodynamic response function (HRF), a model of the change in blood-oxygen-level-dependent signal through time.

Figure 2

Sample stimuli from a single trial of the DSST.

Figure 3

Individual and group HRFs modeled in bilateral (A) BA 4 during BPT performance, (B) BA 17 during BPT performance, (C) BA 4 during DSST performance, (D) BA 9 during DSST performance, and (E) BA 17 during DSST performance. Individual HRFs are in lighter blue (healthy controls) and orange (MS patients), and group HRFs are darker, bolder curves.

Figure 4

Relationships between performance (as measured by RT on the DSST) and (A) peak amplitude and (B) TTP in bilateral BA 9. Lines represent the best fit to the data using least-squares linear regression. Healthy controls are in blue, and MS patients are in orange.