Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder

Umesawa, Yumi; Matsushima, Kanae; Atsumi, Takeshi; Kato, Toshihiro; Fukatsu, Reiko; Wada, Makoto; Ide, Masakazu

doi:10.1007/s10803-020-04382-x

Cited by 19 publications

(13 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SMA is thought to be essential for coordinated body movements (Roland et al, 1980;Tanji et al, 1988;Sumner and Husain, 2008). In agreement with our recent report, the present study's finding indicates that reduced GABA+ in the SMA may reflect complicated motor disability in ASD (Umesawa et al, 2020). Prior work has found that GABA concentrations in V1 did not differ between adults with ASD and controls, but rather were associated with functional measures that characterized that population (Robertson et al, 2016).…”

Section: Discussionsupporting

confidence: 92%

GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability

et al. 2020

Self Cite

View full text Add to dashboard Cite

Individuals with autism spectrum disorder (ASD) often exhibit abnormal processing of sensory inputs from multiple modalities and higher-order cognitive/behavioral response to those inputs. Several lines of evidence suggest that altered γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, is a central characteristic of the neurophysiology of ASD. The relationship between GABA in particular brain regions and atypical sensory processing in ASD is poorly understood. We therefore employed 1 H magnetic resonance spectroscopy (1 H-MRS) to examine whether GABA levels in brain regions critical to higher-order motor and/or multiple sensory functions were associated with abnormal sensory responses in ASD. We evaluated atypical sensory processing with a clinically-validated assessment tool. Furthermore, we measured GABA levels in four regions: one each in the primary visual cortex, the left sensorimotor cortex, the left supplementary motor area (SMA), and the left ventral premotor cortex (vPMC). The latter two regions are thought to be involved in executing and coordinating cognitive and behavioral functions in response to multisensory inputs. We found severer sensory hyper-responsiveness in ASD relative to control participants. We also found reduced GABA concentrations in the left SMA but no differences in other regions of interest between ASD and control participants. A correlation analysis revealed a negative association between left vPMC GABA and the severity of sensory hyper-responsiveness across all participants, and the independent ASD group. These findings suggest that reduced inhibitory neurotransmission (reduced GABA) in a higher-order motor area, which modulates motor commands and integrates multiple sensory modalities, may underlie sensory hyper-responsiveness in ASD.

show abstract

Section: Discussionsupporting

confidence: 92%

GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Again, as shown in Figure 2 A, the amplitude of N45 component of spTMS was smaller in the OLD group and SCZ group (especially significantly lower in the OLD group) than in the YNG group, suggesting a relative decrease in GABA A receptor-mediated neurophysiological function. Thus, the decline in inhibitory neurophysiological function due to age-related changes as well as the pathophysiology of schizophrenia may affect the impairment of coordinated motor skills among motor control [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Single-Pulse Transcranial Magnetic Stimulation-Evoked Potential Amplitudes and Latencies in the Motor and Dorsolateral Prefrontal Cortex among Young, Older Healthy Participants, and Schizophrenia Patients

Noda

Barr

Zomorrodi

et al. 2021

JPM

View full text Add to dashboard Cite

Background: The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) allows for non-invasive investigation of cortical response and connectivity in human cortex. This study aimed to examine the amplitudes and latencies of each TMS-evoked potential (TEP) component induced by single-pulse TMS (spTMS) to the left motor (M1) and dorsolateral prefrontal cortex (DLPFC) among healthy young participants (YNG), older participants (OLD), and patients with schizophrenia (SCZ). Methods: We compared the spatiotemporal characteristics of TEPs induced by spTMS among the groups. Results: Compared to YNG, M1-spTMS induced lower amplitudes of N45 and P180 in OLD and a lower amplitude of P180 in SCZ, whereas the DLPFC-spTMS induced a lower N45 in OLD. Further, OLD demonstrated latency delays in P60 after M1-spTMS and in N45-P60 over the right central region after left DLPFC-spTMS, whereas SCZ demonstrated latency delays in N45-P60 over the midline and right central regions after DLPFC-spTMS. Conclusions: These findings suggest that inhibitory and excitatory mechanisms mediating TEPs may be altered in OLD and SCZ. The amplitude and latency changes of TEPs with spTMS may reflect underlying neurophysiological changes in OLD and SCZ, respectively. The spTMS administered to M1 and the DLPFC can probe cortical functions by examining TEPs. Thus, TMS-EEG can be used to study changes in cortical connectivity and signal propagation from healthy to pathological brains.

show abstract

“…Inhibitory γ-amino butyric acid (GABA)ergic signaling controls the excitability of neuronal networks (Roth and Draguhn, 2012). Deficits in GABAergic neurotransmission are associated with 4 neurodevelopmental disorders, including attention deficit / hyperactivity disorder (Edden et al, 2012), developmental co-ordination disorder (Umesawa et al, 2020), and depressive disorders (Luscher et al, 2011). GABAergic neurotransmission also plays a key role in regulating food intake (Meng et al, 2016;Xu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Neuronal growth regulator 1 (NEGR1) promotes synaptic targeting of glutamic acid decarboxylase 65 (GAD65)

Tan

Kozlova

et al. 2022

Preprint

View full text Add to dashboard Cite

Neuronal growth regulator 1 (NEGR1) is a glycosylphosphatidylinositol-anchored cell adhesion molecule encoded by an obesity susceptibility gene. We demonstrate that NEGR1 accumulates in GABAergic inhibitory synapses in hypothalamic neurons, a GABA-synthesizing enzyme GAD65 attaches to the plasma membrane, and NEGR1 promotes clustering of GAD65 at the synaptic plasma membrane. GAD65 is removed from the plasma membrane with newly formed vesicles. The association of GAD65 with vesicles results in increased GABA synthesis. In NEGR1 deficient mice, the synaptic targeting of GAD65 is decreased, the GABAergic synapse densities are reduced, and the reinforcing effects of food rewards are blunted. In mice fed a high fat diet, levels of NEGR1 are increased and GAD65 abnormally accumulates at the synaptic plasma membrane. Our results indicate that NEGR1 regulates a previously unknown step required for synaptic targeting and functioning of GAD65, which can be affected by bidirectional changes in NEGR1 levels causing disruptions in the GABAergic signaling controlling feeding behavior.

show abstract

Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder

Cited by 19 publications

References 76 publications

GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability

GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability

Single-Pulse Transcranial Magnetic Stimulation-Evoked Potential Amplitudes and Latencies in the Motor and Dorsolateral Prefrontal Cortex among Young, Older Healthy Participants, and Schizophrenia Patients

Neuronal growth regulator 1 (NEGR1) promotes synaptic targeting of glutamic acid decarboxylase 65 (GAD65)

Contact Info

Product

Resources

About