“Brain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisited”

Brix, Maiken K.; Ersland, Lars; Hugdahl, Kenneth; Grüner, Renate; Posserud, Maj-Britt; Hammar, Åse; Craven, Alexander R.; Noeske, Ralph; Evans, Ceri; Walker, Hanne Bjørg; Midtvedt, Tore; Beyer, Mona K.

doi:10.3389/fnhum.2015.00365

Cited by 49 publications

(61 citation statements)

References 66 publications

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“…Specifically, higher SRS‐2 scores (indicative of greater ASD symptomatology) were associated with reduced concentrations of GABA+ in the VIS. This finding is consistent with previous findings linking reductions in GABA to increases in ASD symptoms [Brix et al, ; Carvalho Pereira et al, ]. However, in light of the inverse relationship between VIS GABA+ and VST performance, this result appears to be conflicting, especially given that prior reports have shown that faster, more efficient search is related to ASD symptom severity [Joseph et al, ; Keehn et al, ].…”

Section: Discussionsupporting

confidence: 89%

“…Finally, VIS was chosen to determine whether superior search in ASD is associated with enhanced discrimination [O'Riordan & Plaisted, ], as occipital GABA levels are associated with orientation perceptual thresholds [Edden et al, ; Song et al, ]. Finally, because others have hypothesized that an E/I imbalance may contribute to the development of ASD [Hussman, ; Rubenstein & Merzenich, ], and prior findings have shown an association between GABA and ASD symptom severity [Brix et al, ; Carvalho Pereira, Violante, Mouga, Oliveira, & Castelo‐Branco, ] we examined the relationship between GABA levels and measures of ASD symptomatology.…”

Section: Introductionmentioning

confidence: 99%

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A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

et al. 2020

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Although diagnosed on the basis of deficits in social communication and interaction, autism spectrum disorder (ASD) is also characterized by superior performance on a variety of visuospatial tasks, including visual search. In neurotypical individuals, region‐specific concentrations of the inhibitory neurotransmitter gamma‐aminobutyric acid (GABA) are associated with individual differences in attention and perception. While it has been hypothesized that ASD may be associated with an excitatory–inhibitory imbalance, it remains unclear how this may contribute to accelerated visual search performance in individuals with ASD. To investigate this, 21 children with ASD and 20 typically developing children participated in a visual search task and a magnetic resonance spectroscopy study to detect neurochemical concentrations, including GABA. Region‐specific neurochemicals were examined in the right frontal eye fields, right temporal–parietal junction (rTPJ), and bilateral visual cortex (VIS). GABA concentrations did not differ between groups; however, in children with ASD, greater GABA concentration in the VIS was related to more efficient search. Additionally, lower VIS GABA levels were also associated with increased social impairment. Finally, we found reduced N‐acetyl aspartate, total creatine, glutamate and glutamine (Glx), GABA/Glx in the rTPJ, suggestive of neuronal dysfunction in a critical network hub. Our results show that GABA concentrations in the VIS are related to efficient search in ASD, thus providing further evidence of enhanced discrimination in ASD. Autism Res 2020, 13: 550–562. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Children with autism spectrum disorder (ASD) often perform better than their non‐ASD peers on visual search tasks; however, it is unclear how they achieve this superior performance. Using magnetic resonance spectroscopy to measure neurochemicals in the brain, we found that the level of one, gamma‐aminobutyric acid, in the visual cortex was directly related to search abilities in children with ASD. These results suggest that faster search may relate to enhanced perceptual functioning in children with ASD.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

et al. 2020

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“…Moreover, previous non-invasive 1 H-MRS studies reported increased cerebral concentrations of Glu in Heschl’s gyrus and the anterior cingulate cortex (Brown et al, 2013; Joshi et al, 2013). Moreover, decreased concentrations of GABA in anterior cingulate cortex, motor and auditory cortex, frontal lobe and Heschl’s gyrus (Cochran et al, 2015; Gaetz et al, 2014; Harada et al, 2011; Kubas et al, 2012; Rojas et al, 2014) are reported, supporting that an imbalanced E/I system exists in individuals with ASD (Brix et al, 2015). …”

Section: Introductionmentioning

confidence: 83%

Altered neurotransmitter metabolism in adolescents with high-functioning autism

Drenthen

Barendse

Aldenkamp

et al. 2016

Psychiatry Research: Neuroimaging

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Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few 1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using 1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.

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“…The balance of the excitatory and inhibitory impulses may determine the GABAergic cell activity [18,41]. Correlation between GABA and glutamate layers in prefrontal cortices [41] might be an indicator of the relationship between excitatory and inhibitory neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

“…Correlation between GABA and glutamate layers in prefrontal cortices [41] might be an indicator of the relationship between excitatory and inhibitory neurotransmission. Since the excitatory neurotransmission is degraded in neurodevelopmental disorders, activity of the GABAergic cells and GABA levels might be altered in order to protect the balance between excitatory and inhibitory neurotransmission [41-43]. …”

Section: Discussionmentioning

confidence: 99%

Perisylvian GABA levels in schizophrenia and bipolar disorder

Atagün

Sikoglu

Soykan

et al. 2017

Neuroscience Letters

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The aim of this study is to measure GABA levels of perisylvian cortices in schizophrenia and bipolar disorder patients, using proton magnetic resonance spectroscopy (1H-MRS). Patients with schizophrenia (n=25), bipolar I disorder (BD-I; n=28) and bipolar II disorder (BD-II; n=20) were compared with healthy controls (n=30). 1H-MRS data was acquired using a Siemens 3 Tesla whole body scanner to quantify right and left perisylvian structures’ (including superior temporal lobes) GABA levels. Right perisylvian GABA values differed significantly between groups [χ2=9.62, df: 3, p = 0.022]. GABA levels were significantly higher in the schizophrenia group compared with the healthy control group (p=0.002). Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with right hemisphere GABA levels (r2=0.68, p=0.006, n=33). GABA levels are elevated in the right hemisphere in patients with schizophrenia in comparison to bipolar disorder and healthy controls. The balance between excitatory and inhibitory controls over the cortical circuits may have direct relationship with GABAergic functions in auditory cortices. In addition, GABA levels may be altered by brain regions of interest, psychotropic medications, and clinical stage in schizophrenia and bipolar disorder.

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“Brain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisited”

Cited by 49 publications

References 66 publications

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

Altered neurotransmitter metabolism in adolescents with high-functioning autism

Perisylvian GABA levels in schizophrenia and bipolar disorder

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