Are glutamate and lactate increases ubiquitous to physiological activation? A 1H functional MR spectroscopy study during motor activation in human brain at 7Tesla

Abstract

a b s t r a c t a r t i c l e i n f oRecent studies at high field (7 Tesla) have reported small metabolite changes, in particular lactate and glutamate (below 0.3 μmol/g) during visual stimulation. These studies have been limited to the visual cortex because of its high energy metabolism and good magnetic resonance spectroscopy (MRS) sensitivity using surface coil. The aim of this study was to extend functional MRS (fMRS) to investigate for the first time the metabolite changes during motor activation at 7 T. Small but sustained increases in lactate (0.17 μmol/g ± 0.05 μmol/g, p b 0.001) and glutamate (0.17 μmol/g ± 0.09 μmol/g, p b 0.005) were detected during motor activation followed by a return to the baseline after the end of activation. The present study demonstrates that increases in lactate and glutamate during motor stimulation are small, but similar to those observed during visual stimulation. From the observed glutamate and lactate increase, we inferred that these metabolite changes may be a general manifestation of the increased neuronal activity. In addition, we propose that the measured metabolite concentration increases imply an increase in ΔCMR O2 that is transiently below that of ΔCMR Glc during the first 1 to 2 min of the stimulation.© 2014 Elsevier Inc. All rights reserved. IntroductionFunctional MR spectroscopy (fMRS) provides direct insights into brain metabolism by investigating the metabolic response of the brain to a physiological stimulus. The high spectral resolution and signal-tonoise ratio (SNR) of fMRS at high field (N3 Tesla) improve the accuracy and precision of the quantification of many brain metabolites (Mekle et al., 2009;Tkac et al., 2001Tkac et al., , 2009. In addition to the increased chemical shift dispersion, a high time resolution is of advantage for the characterization of the small transient changes observed. Recent fMRS studies (Lin et al., 2012;Mangia et al., 2007b;Schaller et al., 2013) at high field (7 Tesla) reported small metabolite concentration changes during visual stimulation (around 0.2 μmol/g). In particular, a very small lactate concentration increase between 10 and 23% has been observed. Recently, functional diffusion-weighted MRS has been used to investigate metabolite ADC changes as a potential consequence of micro structural changes during activation (Branzoli et al., 2013).The lactate increase observed during visual stimulation has been suggested to explain the mismatch of cerebral metabolic rate of change for glucose (ΔCMR Glc ) (or cerebral blood flow, CBF) and cerebral metabolic rate of change for oxygen (ΔCMR O2 ) during brain activation. However, many studies have reported different results concerning the transient mismatch of ΔCMR Glc , CBF and ΔCMR O2 during functional activity (reviewed in Buxton (2010)). The characterization of these changes has been reported in positron emission tomography (PET) (Fox and

Neurochemical and BOLD Responses during Neuronal Activation Measured in the Human Visual Cortex at 7 Tesla

“…Similar changes of Glu and Lac have also been reported in the motor cortex. 5 The observed functional changes of metabolite concentrations support an overall increase in oxidative energy metabolism during neuronal activation. 6 In particular, the opposite changes in Glc and Lac concentrations are thought to reflect increased metabolic rate of Glc utilization and activation of the aerobic glycolytic pathway in brain cells.…”

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

“…Lactate and choline levels are altered in chronic pro-neuroinflammatory conditions [39, 64], but also conditions not necessarily associated with neuroinflammation. For example, lactate levels are altered by phasic changes in neural activity [65, 66], metabolic processes [67-69], and impaired blood supply (ischemia/hypoxia; i.e., stroke [70, 71]). Similarly, brain choline levels are influenced by dietary choline consumption [72] and psychiatric comorbidities [73, 74].…”

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

“…This methodology can be used in both clinical settings (e.g., Prichard et al, 1991; Rothman et al, 1992; Gruetter et al, 1994, 1998a, 2001; Shen et al, 1999; Gruetter, 2002; Lebon et al, 2002; de Graaf et al, 2004; Mangia et al, 2007; Oz et al, 2007, 2015; Lin et al, 2012; Schaller et al, 2013, 2014; Bednařík et al, 2015) and pre-clinical studies (e.g., Mason et al, 1992; Hyder et al, 1996, 1997; Sibson et al, 1998, 2001; Choi et al, 2002; Henry et al, 2002; Patel et al, 2004, 2005a; Deelchand et al, 2009; Duarte and Gruetter, 2013; Duarte et al, 2011, 2015; Mishkovsky et al, 2012; Just et al, 2013; Bastiaansen et al, 2013, 2015; Lanz et al, 2014; Sonnay et al, 2015, 2016, 2017). However, in most animal applications it requires anesthesia, which can modify the coupling between neuronal activity, brain metabolism and vascular regulation of blood flow (Masamoto and Kanno, 2012; Sonnay et al, 2017, and references therein).…”

“…The main challenge associated with 1 H MRS is the complexity of the neurochemical profile composed of several overlapping metabolite signals on a relatively small frequency range (i.e., 4–5 ppm) that is to be analyzed (de Graaf, 1998). An extension of this technique is 1 H functional MRS (fMRS) that focuses on time-dependent changes in metabolite concentrations, which are associated with metabolic pathways during brain activity (Prichard et al, 1991; Mangia et al, 2007; Lin et al, 2012; Just et al, 2013; Schaller et al, 2013, 2014; Bednařík et al, 2015). The difficulty associated with the detection of small concentration changes occuring during neuronal activation can yet be overcome by using high magnetic field MR system (≥9.4 T) to increase spectral resolution and sensitivity.…”