Sensorimotor cortex neurometabolite levels as correlate of motor performance in normal aging: evidence from a ¹H-MRS study

Abstract

Aging is associated with gradual alterations in the neurochemical characteristics of the brain, which can be assessed in-vivo with proton-magnetic resonance spectroscopy (¹H-MRS). However, the impact of these age-related neurochemical changes on functional motor behavior is still poorly understood. Here, we address this knowledge gap and specifically focus on the neurochemical integrity of the left sensorimotor cortex (SM1) and the occipital lobe (OCC), as both regions are main nodes of the visuomotor network underlying bimanual control. ¹H-MRS data and performance on a set of bimanual tasks were collected from a lifespan (20–75 years) sample of 86 healthy adults. Results indicated that aging was accompanied by decreased levels of N-acetylaspartate (NAA), glutamate-glutamine (Glx), creatine ​+ ​phosphocreatine (Cr) and myo-inositol (mI) in both regions, and decreased Choline (Cho) in the OCC region. Lower NAA and Glx levels in the SM1 and lower NAA levels in the OCC were related to poorer performance on a visuomotor bimanual coordination task, suggesting that NAA could serve as a potential biomarker for the integrity of the motor system supporting bimanual control. In addition, lower NAA, Glx, and mI levels in the SM1 were found to be correlates of poorer dexterous performance on a bimanual dexterity task. These findings highlight the role for ¹H-MRS to study neurochemical correlates of motor performance across the adult lifespan.

Introduction

Normal aging is associated with gradual alterations in structural and neurochemical characteristics of the brain, the latter of which can be assessed in-vivo by the application of proton-magnetic resonance spectroscopy (¹H-MRS). Changes in the regional levels of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), gamma-aminobutyric acid (GABA), and glutamate-glutamine complex (Glx) have been identified as potential biomarkers of disease progression in neurodegenerative disorders and dementia (Ben Salem et al., 2008; Block et al., 1998; Bonneville et al., 2002; Ding et al., 2008; Duarte et al., 2012; Kalra et al., 2006; Kantarci et al., 2007; Weerasekera et al., 2018; Zanigni et al., 2015). In healthy human volunteers, in-vivo quantification of brain neurometabolites with ¹H-MRS typically shows age-related declines in regional levels of multiple neurometabolites, including NAA, Glx, creatine ​+ ​phosphocreatine (Cr), and GABA and increases in the levels of Cho and mI (Boumezbeur et al., 2010; Ding et al., 2016; Gao et al., 2013; Grachev and Apkarian, 2001; Grachev et al., 2001; Haga et al., 2009; Hermans et al., 2018a; Maes et al., 2017; Porges et al., 2017; Valenzuela et al., 2000; Zahr et al., 2013). These alterations may play a pivotal role as mediators of progressive performance declines observed during aging in an apparently healthy population.

Considering that neurochemical alterations could be indicative of neurodegenerative processes at the neuronal network levels, one would expect to find an association between age-related changes in the regional levels of GABA, NAA, Cho, mI, and Glx (among other neurochemicals and/or neurotransmitters) and degraded motor performance (Zahr et al., 2013; Hermans et al., 2018b). However, very little attention has been paid so far to the age-related declines in motor functioning, and in complex motor tasks (e.g., bimanual coordination) in particular. The current study will address this critical knowledge gap by examining the associations between age-related changes in the integrity of neurochemical systems in the left primary sensorimotor (SM1) and occipital (OCC) cortical regions and performance changes across two specific bimanual tasks: a visuomotor bimanual coordination task (BCT) and bimanual Purdue pegboard task (PPT). Both tasks are useful for studying the associations between neurodegenerative changes in the aging brain and performance changes that could be attributed to suboptimal operation of the cortical visuomotor network underlying bimanual coordination (Fujiyama et al., 2016; King et al., 2017; Serbruyns et al., 2015; Sisti et al., 2011). The SM1 and OCC were selected on the basis of previous task-related fMRI studies on bimanual tracking tasks under visual guidance (e.g., Beets et al., 2015; Santos Monteiro et al., 2017), showing that both regions are principal nodes of the sensorimotor system supporting visuomotor control.

In an early study of our group using a variant of the BCT (Fujiyama et al., 2016), we demonstrated that older adults who showed performance declines in more difficult bimanual conditions also showed a decreased ability to regulate the interaction between dorsolateral prefrontal cortex and the primary motor cortex (M1). In line with these findings, we expected that (1) lower Glx levels in the sensorimotor voxel will be related to decreased performance on BCT as both excitatory and inhibitory interactions between M1 and other brain regions are expected to rely primarily on activation of glutamatergic transmission (Chen, 2004; Levin et al., 2014; Liuzzi et al., 2010; Perez and Cohen, 2008). In addition, we expected that (2) age-related performance declines in BCT (and bimanual PPT) will be related to decreases in the level of NAA, which is generally considered to be associated with GM loss (Ding et al., 2016) and WM microstructural declines (Grossman et al., 2015; Wijtenburg et al., 2013) that may hinder bimanual control. Finally, we expected that (3) higher levels of Cho and mI would be related to poorer performance on both tasks, since increased concentrations of these metabolites have been associated with cerebral infarction under various neuropathological conditions or diseases (Soares and Law, 2009). However, there is a certain degree of controversy in the literature regarding the effects of normal healthy aging on mI and Cho concentrations (Cichocka and Bereś, 2018; Cleeland et al., 2019). Therefore, it was not possible to form clear hypotheses about the nature of the relationship between age-related changes in regional concentrations of mI or Cho and performance on the two bimanual tasks.