Abstract
Suboptimal inhibitory control is a major factor contributing to motor/cognitive deficits in older age and pathology. Here, we provide novel insights into the neurochemical biomarkers of inhibitory control in healthy young and older adults and highlight putative neurometabolic correlates of deficient inhibitory functions in normal aging. Age-related alterations in levels of glutamate–glutamine complex (Glx), N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mIns) were assessed in the right inferior frontal gyrus (RIFG), pre-supplementary motor area (preSMA), bilateral sensorimotor cortex (SM1), bilateral striatum (STR), and occipital cortex (OCC) with proton magnetic resonance spectroscopy (1H-MRS). Data were collected from 30 young (age range 18–34 years) and 29 older (age range 60–74 years) adults. Associations between age-related changes in the levels of these metabolites and performance measures or reactive/proactive inhibition were examined for each age group. Glx levels in the right striatum and preSMA were associated with more efficient proactive inhibition in young adults but were not predictive for reactive inhibition performance. Higher NAA/mIns ratios in the preSMA and RIFG and lower mIns levels in the OCC were associated with better deployment of proactive and reactive inhibition in older adults. Overall, these findings suggest that altered regional concentrations of NAA and mIns constitute potential biomarkers of suboptimal inhibitory control in aging.
Highlights
We primarily focused on subregions of the prefrontal-striatal pathways and visuomotor pathways, which are functionally associated with age-induced deficits in inhibitory control of movements (e.g., Coxon et al 2012, 2016; Leunissen et al 2016; Hermans et al 2018)
We have shown that the processes associated with movement initiation and proactive inhibition depend on the integrity of the glutamatergic systems in the pre-supplementary motor area (preSMA), the right inferior frontal gyrus, and the striatum
Based on the present MRS data, we suggest that changes in neurometabolite concentrations associated with structural integrity of the fronto-basal-ganglia pathways, NAA and mIns, are closely associated to motor inhibition declines in normal aging
Summary
Inhibition plays a critical role in the control of many cognitive and motor functions (Logan et al 1984; Garavan et al 1999; Coxon et al 2006; Aron 2007; Coxon et al 2012; Fujiyama, Hinder, Schmidt, Garry, et al 2012a, Fujiyama, Hinder, Schmidt, Tandonnet, et al 2012b; Coxon et al 2016; Hermans et al 2018; Hermans et al 2019; Cuypers et al 2020; for reviews see Levin et al 2014; Tan et al 2019). Motor inhibitory processes can be classified as reactive (i.e., cessation of a motor response that is already in progress) or proactive (i.e., inhibitory control mechanisms engaged prior to the initiation of a response) (Logan et al 1984; Aron 2011; Leunissen et al 2016; Meyer and Bucci 2016). Proactive inhibition is expected to be more dominant when a potential need for action cancelation may require a reactive response (Leunissen et al 2016; Meyer and Bucci 2016); it is viewed as a process that is generated according to the goals of the subject rather than by an external signal (Aron 2011; Braver 2012)
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