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Written by ︱ Fu Huimin, editor in charge ︱ Wang Sizhen In autism spectrum disorder (ASD), abnormal sensory processing ability is one of the prominent clinical features of the group[1]
.
For example, compared with the non-ASD population, ASD patients have enhanced local visual processing ability, slower binocular rivalry, reduced spatial inhibition, and decreased global motor perception [2-5]
.
Studies have shown that, at the neurobiological level, abnormalities in the excitatory-inhibitory balance, especially the inhibitory γ-aminobutyric acid (GABA) pathway, may be involved in the abnormal process of visual processing in ASD play an important role in [6-8]
.
The association between GABA concentrations and visual processing has been demonstrated in non-ASD populations, but not in ASD
.
The role of GABA receptors in the process of visual inhibition is crucial
.
Of the two subtypes of GABA receptors, GABAA receptors elicit "phasic" rapid postsynaptic inhibition and "tonic" extracellular inhibitory responses [9], and GABAB receptors coordinate neuronal excitability "Slow" changes, but also can quickly inhibit neural network activity [10]
.
Currently, it remains unclear whether activation of GABA receptors can modulate the visual perception differences in ASD
.
On January 5, 2022, Professor Gráinne M.
McAlonan's group at King's College London published a research paper entitled "GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder" in Science Translational Medicine
.
The authors found that differences in the GABA pathway are responsible for abnormal visual processing in ASD patients, and high doses of GABAB receptor agonists abolish these differences, which has important implications for the development of personalized interventions based on sensory differences in ASD
.
This study included 19 ASD patients and 25 healthy individuals, who were divided into 6 groups after treatment with placebo or baclofen (a GABAB receptor agonist): control group - placebo group (Control_P), control group - low dose group (Control_L), control group - high dose group (Control_H), autism - placebo group (ASD_P), autism - low dose group (ASD_L), autism - high dose group (ASD_H)
.
First, they found no difference in baseline GABA+ concentrations in the medial occipital cortex between 15 ASD and 18 control participants
.
The proportion of non-zero foreground contrast-evoked increase in SSVEP was then defined by EEG recordings of steady-state visual evoked potentials (SSVEPs) elicited by peripheral visual field stimuli, including circularly blinking Gabor foreground gratings and static backgrounds in specific configurations is the variable θ
.
Where the foreground grating has a contrast of 0% (F0), 30% (F30) or 100% (F100), and the background pattern has a contrast of 0% (B0) or 100% (B100)
.
The results showed that there were significant group differences in θ in the Control_P group and the ASD_P group
.
In the Control_L condition, background disturbance and foreground contrast still significantly affect θ, but the Control_H condition destroys this effect
.
Under the ASD_L condition, the foreground contrast can significantly affect θ, but the background disturbance cannot; under the ASD_H condition, the background disturbance and foreground contrast significantly affect θ (Fig.
1)
.
These results suggest that excessive GABAB activation disrupts sensitivity to visual stimuli in non-ASD individuals and enhances sensitivity to visual stimuli in ASD individuals
.
Figure 1 SSVEP responses to visual stimuli in six participating groups (Source: Huang et al.
, Sci Transl Med.
2022) To verify the role of background distraction in SSVEP’s response to foreground, researchers compared background distraction to each foreground The effect of the condition is defined as "surround suppression" (SS)
.
Significant differences were found in SSF100, but not SSF30, between Control_P and ASD_P groups (Fig.
2)
.
Thus, background interference suppressed the control group but not the ASD group's SSVEP response to F100
.
Figure 2 "Peripheral inhibition" in ASD and control groups (Image source: Huang et al.
, Sci Transl Med.
2022) Next, the authors determined the correlation between visual acuity during background interference and occipital GABA+ concentrations in the placebo group.
correlation
.
It was found that in the Control_P group, there was a clear correlation between theta and GABA+ concentrations when the foreground contrast was high and there was background interference
.
In contrast, there was no correlation between theta and GABA+ concentrations in the ASD_P group under any contrast conditions (Fig.
3)
.
This suggests that there is no definite association between GABA and SSVEP
.
Figure 3.
Correlation between GABA+ concentration and SSVEP response (Source: Huang et al.
, Sci Transl Med.
2022) Finally, the authors examined the "" Sensitivity Index"
.
Analysis showed that high doses of baclofen significantly affected the transition of sensitivity indices in ASD participants, and 100% of the ASD group showed an increase in Δθ (Figure 4)
.
Figure 4 In ASD participants, the individual sensitivity index after drug treatment (Source: Huang et al.
, Sci Transl Med.
2022) Conclusion and discussion, inspiration and prospect This study proves that ASD patients have GABA-dependent, Abnormal visual processing, which can be reversed by targeting GABAB receptors
.
Activation of GABAB receptors has presynaptic and postsynaptic effects, which can cause inhibition and release [11]
.
In the present study, high doses of baclofen induced neurotypical responses and sensitivity to different visual stimuli in patients with ASD
.
Therefore, increasing GABAB may restore the excitation-inhibitory balance and drive sensory perception, which is consistent with previous findings that GABAB receptors support changes in neuronal adaptive activity [11]
.
However, the results of this study do not address the clinical efficacy of baclofen, nor which core ASD symptoms this effect targets
.
Second, the authors also do not specify in which stage of the GABAergic difference occurs in ASD, a neurodevelopmental disorder in children where brain development is governed by multiple "cascades" of sensitive periods of distinct neural circuits/complex functions composition, these functions persist throughout childhood and adolescence [12]
.
And it is worth considering whether uniform stimuli can indiscriminately enter higher-order processing in the visual cortex of ASD? If so, the ability to detect and low-contrast stimuli in high-interference conditions may sometimes be beneficial and support the acquisition of specific skills; however, it may also contribute to the sensory "overload" and distress common in ASD patients
.
Link to the original text: https:// Selected articles from previous issues[1] Sci Adv︱Xu Yong/Xu Pingping/He Yanlin collaborated to discover that estrogen receptor neurons regulate body temperature and movement [2] PNAS︱Han Chun's group reveals a new mechanism of neuronal degeneration caused by external phagocytosis [3] Nat Neurosci︱VTA dopaminergic neurons are involved in encoding social prediction error and social reinforcement learning [4] Nature︱New Discover! Inflammatory lymphocytes or new targets mediating CNS inflammation? 【5】Neurosci Bull︱Hu Bo’s research group reveals that the deep cerebellar nucleus neurons projecting to the ventromedial thalamus are specifically involved in the regulation of combined sensory-motor learning behavior 【6】Nat Neurosci︱Wu Longjun research group reveals the key pathological proteins of ALS A new ligand for TDP-43 - TREM2【7】Cereb Cortex︱Luo Yuejia's team revealed the cognitive control mechanism under uncertain expectations conditions of anxious individuals 【8】PNAS︱Xiao Bo's research group revealed a new mechanism for regulating the development of myelin in the central nervous system Mechanism 【9】Science︱Neuronal mechanism controlling behavioral motivation 【10】Sci Adv︱Chen Zhong team proposed a new idea for epilepsy drug treatment: Electrically responsive polydopamine nano-drug delivery system References (swipe up and down to view) 【1】DR Simmons , AE Robertson, LS McKay, E.
Toal, P.
McAleer, FE Pollick, Vision in autism spectrum disorders.
Vision Res.
49, 2705–2739 (2009).
【2】S.
Dakin, U.
Frith, Vagaries of visual perception in autism.
Neuron 48, 497–507 (2005).
[3] CE Robertson, DJ Kravitz, J.
Freyberg, S.
Baron-Cohen, CI Baker, Slower rate of binocular rivalry in autism.
J.
.
For example, compared with the non-ASD population, ASD patients have enhanced local visual processing ability, slower binocular rivalry, reduced spatial inhibition, and decreased global motor perception [2-5]
.
Studies have shown that, at the neurobiological level, abnormalities in the excitatory-inhibitory balance, especially the inhibitory γ-aminobutyric acid (GABA) pathway, may be involved in the abnormal process of visual processing in ASD play an important role in [6-8]
.
The association between GABA concentrations and visual processing has been demonstrated in non-ASD populations, but not in ASD
.
The role of GABA receptors in the process of visual inhibition is crucial
.
Of the two subtypes of GABA receptors, GABAA receptors elicit "phasic" rapid postsynaptic inhibition and "tonic" extracellular inhibitory responses [9], and GABAB receptors coordinate neuronal excitability "Slow" changes, but also can quickly inhibit neural network activity [10]
.
Currently, it remains unclear whether activation of GABA receptors can modulate the visual perception differences in ASD
.
On January 5, 2022, Professor Gráinne M.
McAlonan's group at King's College London published a research paper entitled "GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder" in Science Translational Medicine
.
The authors found that differences in the GABA pathway are responsible for abnormal visual processing in ASD patients, and high doses of GABAB receptor agonists abolish these differences, which has important implications for the development of personalized interventions based on sensory differences in ASD
.
This study included 19 ASD patients and 25 healthy individuals, who were divided into 6 groups after treatment with placebo or baclofen (a GABAB receptor agonist): control group - placebo group (Control_P), control group - low dose group (Control_L), control group - high dose group (Control_H), autism - placebo group (ASD_P), autism - low dose group (ASD_L), autism - high dose group (ASD_H)
.
First, they found no difference in baseline GABA+ concentrations in the medial occipital cortex between 15 ASD and 18 control participants
.
The proportion of non-zero foreground contrast-evoked increase in SSVEP was then defined by EEG recordings of steady-state visual evoked potentials (SSVEPs) elicited by peripheral visual field stimuli, including circularly blinking Gabor foreground gratings and static backgrounds in specific configurations is the variable θ
.
Where the foreground grating has a contrast of 0% (F0), 30% (F30) or 100% (F100), and the background pattern has a contrast of 0% (B0) or 100% (B100)
.
The results showed that there were significant group differences in θ in the Control_P group and the ASD_P group
.
In the Control_L condition, background disturbance and foreground contrast still significantly affect θ, but the Control_H condition destroys this effect
.
Under the ASD_L condition, the foreground contrast can significantly affect θ, but the background disturbance cannot; under the ASD_H condition, the background disturbance and foreground contrast significantly affect θ (Fig.
1)
.
These results suggest that excessive GABAB activation disrupts sensitivity to visual stimuli in non-ASD individuals and enhances sensitivity to visual stimuli in ASD individuals
.
Figure 1 SSVEP responses to visual stimuli in six participating groups (Source: Huang et al.
, Sci Transl Med.
2022) To verify the role of background distraction in SSVEP’s response to foreground, researchers compared background distraction to each foreground The effect of the condition is defined as "surround suppression" (SS)
.
Significant differences were found in SSF100, but not SSF30, between Control_P and ASD_P groups (Fig.
2)
.
Thus, background interference suppressed the control group but not the ASD group's SSVEP response to F100
.
Figure 2 "Peripheral inhibition" in ASD and control groups (Image source: Huang et al.
, Sci Transl Med.
2022) Next, the authors determined the correlation between visual acuity during background interference and occipital GABA+ concentrations in the placebo group.
correlation
.
It was found that in the Control_P group, there was a clear correlation between theta and GABA+ concentrations when the foreground contrast was high and there was background interference
.
In contrast, there was no correlation between theta and GABA+ concentrations in the ASD_P group under any contrast conditions (Fig.
3)
.
This suggests that there is no definite association between GABA and SSVEP
.
Figure 3.
Correlation between GABA+ concentration and SSVEP response (Source: Huang et al.
, Sci Transl Med.
2022) Finally, the authors examined the "" Sensitivity Index"
.
Analysis showed that high doses of baclofen significantly affected the transition of sensitivity indices in ASD participants, and 100% of the ASD group showed an increase in Δθ (Figure 4)
.
Figure 4 In ASD participants, the individual sensitivity index after drug treatment (Source: Huang et al.
, Sci Transl Med.
2022) Conclusion and discussion, inspiration and prospect This study proves that ASD patients have GABA-dependent, Abnormal visual processing, which can be reversed by targeting GABAB receptors
.
Activation of GABAB receptors has presynaptic and postsynaptic effects, which can cause inhibition and release [11]
.
In the present study, high doses of baclofen induced neurotypical responses and sensitivity to different visual stimuli in patients with ASD
.
Therefore, increasing GABAB may restore the excitation-inhibitory balance and drive sensory perception, which is consistent with previous findings that GABAB receptors support changes in neuronal adaptive activity [11]
.
However, the results of this study do not address the clinical efficacy of baclofen, nor which core ASD symptoms this effect targets
.
Second, the authors also do not specify in which stage of the GABAergic difference occurs in ASD, a neurodevelopmental disorder in children where brain development is governed by multiple "cascades" of sensitive periods of distinct neural circuits/complex functions composition, these functions persist throughout childhood and adolescence [12]
.
And it is worth considering whether uniform stimuli can indiscriminately enter higher-order processing in the visual cortex of ASD? If so, the ability to detect and low-contrast stimuli in high-interference conditions may sometimes be beneficial and support the acquisition of specific skills; however, it may also contribute to the sensory "overload" and distress common in ASD patients
.
Link to the original text: https:// Selected articles from previous issues[1] Sci Adv︱Xu Yong/Xu Pingping/He Yanlin collaborated to discover that estrogen receptor neurons regulate body temperature and movement [2] PNAS︱Han Chun's group reveals a new mechanism of neuronal degeneration caused by external phagocytosis [3] Nat Neurosci︱VTA dopaminergic neurons are involved in encoding social prediction error and social reinforcement learning [4] Nature︱New Discover! Inflammatory lymphocytes or new targets mediating CNS inflammation? 【5】Neurosci Bull︱Hu Bo’s research group reveals that the deep cerebellar nucleus neurons projecting to the ventromedial thalamus are specifically involved in the regulation of combined sensory-motor learning behavior 【6】Nat Neurosci︱Wu Longjun research group reveals the key pathological proteins of ALS A new ligand for TDP-43 - TREM2【7】Cereb Cortex︱Luo Yuejia's team revealed the cognitive control mechanism under uncertain expectations conditions of anxious individuals 【8】PNAS︱Xiao Bo's research group revealed a new mechanism for regulating the development of myelin in the central nervous system Mechanism 【9】Science︱Neuronal mechanism controlling behavioral motivation 【10】Sci Adv︱Chen Zhong team proposed a new idea for epilepsy drug treatment: Electrically responsive polydopamine nano-drug delivery system References (swipe up and down to view) 【1】DR Simmons , AE Robertson, LS McKay, E.
Toal, P.
McAleer, FE Pollick, Vision in autism spectrum disorders.
Vision Res.
49, 2705–2739 (2009).
【2】S.
Dakin, U.
Frith, Vagaries of visual perception in autism.
Neuron 48, 497–507 (2005).
[3] CE Robertson, DJ Kravitz, J.
Freyberg, S.
Baron-Cohen, CI Baker, Slower rate of binocular rivalry in autism.
J.
