BOLD hemodynamic response function changes significantly with healthy aging

Abstract

Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18–30 years of age) and 173 older participants (54–74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB’s Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately.

Model-Predicted Balance Between Neural Excitation and Inhibition Was Maintained Despite of Age-Related Decline in Sensory Evoked Local Field Potential in Rat Barrel Cortex

“…Indeed many fMRI studies have shown that the amplitude of the blood-oxygen-level-dependent (BOLD) signal decreases with age (Tekes et al, 2005;Ances et al, 2009;Ward et al, 2015). Particularly interesting is a recent human fMRI study (West et al, 2019) which showed that, under visual stimulation, the BOLD signal in the occipital region of the old adult group had significantly lower peak amplitude, longer peak latency and slower rise slope compared to the young adult group. These age-related changes of the BOLD response were remarkably similar to what we observed in our neural data (Figure 2).…”

The Role of Moderating Variables on BOLD fMRI Response During Semantic Verbal Fluency and Finger Tapping in Active and Educated Healthy Seniors

“…Though, other interpretations exist. For instance, activation of language areas could be related to a carry-over effect specific to the older group due to changes in the deployment of the BOLD response (West et al, 2019). Alternatively, it is possible that older participants remained unconsciously thinking about semantic categories during the performance of the motor task or that they covertly pace themselves using inner speech/sub articulation.…”

Hemodynamic responses are abnormal in isolated cervical dystonia

“…Age was included as a covariate because healthy aging can significantly impact the BOLD response (West et al, 2019). Significance was set to p < 0.05 for these comparisons.…”

“…For the blocked-design fMRI analysis, age, sex, and scanner were included as covariates in the voxel-wise regression analyses. Age was included as a covariate because healthy aging can significantly impact the BOLD response (West et al, 2019). Gender differences in hemodynamic responses have also been reported (Kastrup, Li, Glover, Kruger, & Moseley, 1999;Kaufmann, Elbel, Gossl, Putz, & Auer, 2001;Minhas, Panerai, & Robinson, 2018), and so we included gender as a covariate as well.…”