The contribution of [1H] magnetic resonance spectroscopy to the study of excitation-inhibition in autism

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

“…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.…”

Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties

“…Initial correlational analyses provide preliminary evidence to 400 suggest an interrelationship between right STC glutamate/GABA+ ratios, right MMF latency 401 and symptom domains associated with psychosocial function, such that longer MMF latency 402 was associated with more severe psychosocial deficits, and higher glutamate/GABA+ ratios. contribute to the inconsistencies reported in regional glutamate and GABA 463 concentrations (for review see Ajram et al, 2019;Ford and Crewther, 2016), 464 although, these inconsistencies could be attributed to actual regional differences in Research has also reported various genetic mutations that may affect 467 excitatory-inhibitory processes in schizophrenia, including those seen in autism (e.g., 468 CNTNAP2, SHANK3, neurexin 1), as well as disruption to the glutamate-GABA 469 metabolism enzymes glutaminase and glutamine synthetase (Bruneau et al, 2005). 1H-MRS 470 studies have relatively consistently shown increased glutamate, glutamine and Glx across 471 brain regions, which have been associated with negative symptoms (for a review, see Foss-472 region were associated with slightly smaller MMN amplitude in healthy populations, 490 however the MMN was recorded fronto-centrally (Kompus et al, 2015).…”

Using Connectivity to Explain Autism

“…The work of Butler et al [58] has gone a long way in refuting the "neural noise" or "neural unreliability" hypothesis, which is, to a large degree, isomorphic to Belmonte, Cook et al (2004), at least for the physiology measured by scalp EEG. However, strands of Belmonte, Cook et al persist in the study of GABAergic mechanisms [59], which are not only increasing but serve as one of the theories that is semi-competitive (or yet-to-be-integrated) with the longrange underconnectivity hypothesis. 6 Readers of the ASD-perception and ASD-connectivity literatures will recognize that more efficient processing of small, local features of stimuli accompanying decreased efficiency of global or gestalt percepts is commonly referred to as Weak Central Coherence (WCC) [55].…”

“…Recent work from Roberts' group has begun to combine transmission speed measurements (evoked-response latencies) with DTI measures, in order to bridge these levels of analysis. They further incorporate magnetic resonance spectroscopy (MRS) measures of GABA levels as a proxy of synaptic transmission speed; this inclusion further serves to bridge the connectivity account of ASD with a GABAergic account [59,93]. They show [94] that children with lownormal fractional anisotropy (FA; "white matter integrity") have M50 auditory event-related field (ERF) components predicted by GABA levels (and therefore presumably synaptic transmission), whereas those with yet lower FA values have a correlation between M50 latency and FA values, implicating white matter integrity (Fig.…”

“…Despite these findings, other versions of the inhibition/excitation hypothesis [94] continue to be open lines of exploration, including via increasing study of GABAergic alterations in ASD [59]. SNR may be most useful as a candidate explanation of the attentional differences in ASD.…”