Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS)

Abstract

PurposeProton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger’s syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder.MethodsStudy participants consisted of 34 children with AS (2–12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2–11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum.ResultsIn the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions.ConclusionThe finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

Concentrations of Cortical GABA and Glutamate in Young Adults With Autism Spectrum Disorder

“…The overall pattern of results summarized here, from the current study and others, is that there are no differences in GABA levels in adults with ASD. Considering these findings in light of reports of lower GABA+ in children (notably, only in some studies but not in others; Brix et al, 2015;Carvalho Pereira et al, 2018;Cochran et al, 2015;Drenthen et al, 2016;Goji et al, 2017) raises the possibility that alterations that are observed in childhood in ASD become more typical by adulthood. And indeed, GABA and glutamate balance and function change throughout the development [Corrigan et al, 2013;Ito et al, 2017;Luján, Shigemoto, & López-Bendito, 2005].…”

“…Several recent MRS studies have reported reduced GABA+ concentration in children with ASD, lending support to the E/I imbalance model [Gaetz et al, 2014;Harada et al, 2011;Ito et al, 2017;Kubas et al, 2012;Port et al, 2017;Puts et al, 2017;Rojas, Singel, Steinmetz, Hepburn, & Brown, 2014]. However, others reported no differences in GABA+ levels between children with and without ASD [Brix et al, 2015;Carvalho Pereira, Violante, Mouga, Oliveira, & Castelo-Branco, 2018;Cochran et al, 2015;Drenthen et al, 2016;Goji et al, 2017]. Several studies with adult participants also found no differences in levels of GABA+ in ASD [Ajram et al, 2017;Horder et al, 2018;Kirkovski, Suo, Enticott, Yücel, & Fitzgerald, 2018;Port et al, 2017;Pretzsch et al, 2019;Robertson, Ratai, & Kanwisher, 2016].…”

“…Hence, although the overall trend is for lower GABA+ in ASD, it seems that results are inconsistent, owing perhaps to differences in experimental procedures and analysis methods, regions of interest (ROIs), and sample characteristics, as summarized in several recent reviews [Ajram et al, 2019;Ford & Crewther, 2016;Schür et al, 2016]. In the case of Glx, results are even less conclusive, with studies reporting reduced [Bernardi et al, 2011;Corrigan et al, 2013;DeVito et al, 2007;Hegarty et al, 2018;Horder et al, 2013Horder et al, , 2018Kubas et al, 2012;Tebartz Van Elst et al, 2014], equivalent [Ajram et al, 2017;Aoki et al, 2012;Brix et al, 2015;Carvalho Pereira et al, 2018;Endres et al, 2017;Friedman et al, 2006;Goji et al, 2017;Hardan et al, 2008;Horder et al, 2018;Ito et al, 2017;Libero et al, 2016;Mikkelsen et al, 2017;Robertson et al, 2016], or increased [Bejjani et al, 2012;Brown, Singel, Hepburn, & Rojas, 2013;Doyle-Thomas et al, 2014;Page et al, 2006] levels in ASD. In the current study, we sought to extend previous results by measuring GABA+ and Glx simultaneously using current methodology, in a relatively large sample of well-characterized individuals with ASD, including previously unexamined ROIs, and testing the functional relevance of neurometabolite levels by correlating individual differences in MRS measures with behavior and ASD symptomatology.…”

Correlation between cerebellar metabolism and post-stroke depression in patients with ischemic stroke

“…This result may suggest that the pathogenesis of acute PSD was related to non-neuronal changes. Other studies also showed no differences in cerebellar NAA concentrations in PSD patients compared to a control group [ 33 , 34 ]. However, lower NAA/Cr ratio in the cerebellar hemisphere contralateral to the lesion at 3 months after stroke compared to that at 14 days after stroke indicated that, the pathogenesis of chronic PSD may be related to the abnormal function of neurons and axons, abnormal cell energy metabolism and structural damage.…”

Brain Metabolite Changes After Anodal Transcranial Direct Current Stimulation in Autism Spectrum Disorder

“…They suggested that NAA/Cr deficits in the brain region responsible for executive functions may be associated with social and communication difficulties in ASD (Fujii et al, 2010;Shepherd and Freiwald, 2018). There were also reports showing low levels of Cho in the left inferior anterior cingulate cortex (ACC) (Levitt et al, 2003), low levels of Glx in the right ACC (Bernardi et al, 2011), and decreased NAA, Cho, and mI in the ACC (Goji et al, 2017). Other MRS studies of ASD reported low levels of NAA in the left amygdala (Mori et al, 2013) and low levels of NAA and Glx in the left frontal cortex (Kleinhans et al, 2007).…”