The association between language-based task-functional magnetic resonance imaging hemodynamics and baseline GABA+ and glutamate–glutamine measured in pre-supplementary motor area: A pilot study in an aging model

Abstract

Aging is a natural phenomenon that elicits slow and progressive cerebrovascular and neurophysiological changes that eventually lead to cognitive decline. The objective of this pilot study is to examine the association of GABA+ and glutamate–glutamine (Glx) complex with language-based blood oxygen level dependent (BOLD) hemodynamics in an aging model. More specifically, using standard BOLD we will first attempt to validate whether previously reported findings for BOLD amplitude and resting neurochemical relationships hold in an aging model. Secondly, we will investigate how our recently established neurosensitized task-BOLD energetics relate to resting GABA+ and Glx, especially accounting for titration of task difficulty. To support the above endeavors, we optimize the baseline fitting for edited magnetic resonance spectroscopy (MRS) difference spectra to sensitize GABA+ and Glx concentrations to aging-related differences. We identify a spline-knot spacing of 0.6ppm to yield the optimal aging-related differences in GABA+ and Glx. The optimized MRS values were then graduated to relate to task-BOLD hemodynamics. Our results did not replicate previous findings that relate task-BOLD amplitude and resting GABA+ and Glx. However, we did identify neurochemistry relationships with the vascularly-driven dispersion component of the hemodynamic response function, specifically in older participants. In terms of neuro-sensitized BOLD energetics and the underlying role of GABA+ and Glx, our data suggests that the task demands are supported by both neurometabolites depending on the difficulty of the task stimuli. Another novelty is that we developed task-based functional parcellation of pre-SMA using both groups. In sum, we are the first to demonstrate that multimodal task-fMRI and MRS studies are beneficial to improve our understanding of the aging brain physiology, and to set the platform to better inform approaches for clinical care in aging-related neurovascular diseases. We also urge future studies to replicate our findings in a larger population incorporating a lifespan framework.

ASL MRI informs blood flow to chronic stroke lesions in patients with aphasia

“…Such a result, though counterintuitive, is not beyond the realm of possibility. A theoretical, yet empirically elusive, construct in the stroke literature is the concept of diaschisis ( Carrera and Tononi, 2014 )—defined as “neurophysiological changes that occur distant to a focal brain lesion.” It may be that loss of input and output to a region distal to the lesion may cause an increase in blood flow due to a reduction in inhibitory tone ( Blicher et al, 2015 ), which together (i.e., GABA and CBF) influence cognitive decline ( Krishnamurthy V. et al, 2022 ; Krishnamurthy L. C. et al, 2022 ). Therefore, an increased CBF distal to the lesion may indicate a failure of the network and lead to worse behavioral outcomes.…”

GABA, glutamate and excitatory-inhibitory ratios measured using short-TE STEAM MRS at 7-Tesla: Effects of macromolecule basis sets and baseline parameters

“…Among them, 10 studies explicitly described the DKNTMN that is the minimum spacing of the knots in ppm or equivalent values. Many of the studies investigated and compared different DKNTMN values, but they were equal to or below 1.00 [ 18 , [22] , [23] , [24] , [25] , [26] , [27] , [28] ], and two papers compared those of 0.15 and 5.00 [ 16 , 29 ]. No substantial change was observed in the stiffness of the spline baseline for DKNTMN values higher than 1 [ 18 ], and we investigated in the range of 0.15 to 1.00.…”