Modulation of the Activity of the Cerebellum in Autism (MACA)

Autism Spectrum Disorder Clinical Trial

— MACA  

Official title:

Modulation of the Activity in the Cerebellum With Transcranial Direct Current Stimulation in Autistic Participants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05781412
• Other study ID #: 22064MACA
• Status: Recruiting
• Phase: N/A
• Start date: May 24, 2022
• Est. completion date: October 30, 2024

Study information

• Verified date: April 2023
• Source: Vrije Universiteit Brussel
• Contact: Beatriz Catoira, Msc
• Phone: +32456267472
• Email: Beatriz.catoira[@]vub.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Research on the involvement of the cerebellum in social understanding behavior and the mentalizing brain system has just begun. Knowledge about the neurobiology of social understanding is important for understanding the ways to manipulate these processes. Like cerebral tDCS, cerebellar tDCS could then be used to enhance more complex processes, such as mentalizing, in healthy individuals. It can eventually also be examined as a therapeutic tool for patients with mentalizing difficulties such as patients with ASD. In this study, it is examined whether anodal tDCS at the right posterior cerebellum influences social understanding and which cerebro-cerebellar networks play a role in this process.

Description:

Autism Spectrum Disorders (ASD) are a group of lifelong neurodevelopmental disorders characterized by social and communicative difficulties and repetitive and stereotyped behaviors. Research has shown that cerebellar abnormalities are among the most important etiological factors for ASD. The cerebellum is found to be most frequently involved in tasks where participants must remember or imagine past or future autobiographical events, judge persons or situations based on behavioral sentences, make trait inferences of others using stories, words or faces, and describe persons or objects based on behavioral or object pictures. Recent research has also provided evidence on the involvement of the posterior areas of the cerebellum in social cognition.

Specifically, the areas crus I and crus II, located at the lateral hemispheres of the posterior cerebellum, are associated with more complex cognitive and social processes, such as mentalizing. Mentalizing is the cognitive ability to attribute mental states, such as desires, intentions, and beliefs, to other people. This ability is needed to understand and predict other people's behavior and is the main component of social cognition. Problems with mentalizing, including the attribution of false beliefs to others, are characteristic for autism spectrum disorder (ASD). A sequencing task (that included social and non social conditions) showing that cerebellar patients performed worse than healthy participants.

Facial emotion recognition refers to the ability to derive emotional meaning from facial expressions and has been shown to underlie social competency. Recent literature reviews have reported significant facial emotion recognition impairments in individuals with ASD. These impairments take various forms, such as a reduced accuracy in labeling facial emotions or reduced specificity in rating facial emotions of varying intensity . Thus, there is evidence suggesting that ASD is associated with a selective impairment in facial emotion recognition.

Transcranial direct current stimulation (tDCS) is a noninvasive technique that can produce long-lasting changes in the excitability and spontaneous activity of the stimulated brain areas. Therefore, tDCS is investigated as a possible treatment for different psychiatric diseases. Cerebellar tDCS have shown to also produce prolonged changes successfully at the neural and behavioral level. However, due to the high density of neurons in the cerebellum and diffuse connections to the cerebrum, it is more difficult to understand the working mechanisms of cerebellar as compared to cerebral tDCS. In addition, the electrical current will spread across more neurons in the cerebellum by cerebellar tDCS and will functionally affect the cerebral regions to which these cerebellar neurons are connected as well. Therefore, the type of behavioral effect, such as an improvement of performance after anodal tDCS or an impairment of performance after cathodal tDCS, is harder to predict for cerebellar than cerebral tDCS.

Modulation of social understanding with tDCS has been studied by stimulating the key mentalizing regions mPFC and TPJ. In healthy participants, an improvement on tasks was found that required the enhancement or inhibition of representation of the self or of others, which is important for mentalizing, after anodal tDCS at the TPJ compared to sham tDCS or cathodal tDCS. The effect of cerebellar tDCS on social understanding using action sequences has not yet been examined.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 30, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Participant Inclusion/exclusion criteria:

• Participants must be more than 18 years old

• normal eyesight and hearing;

• Dutch, French or English speaking;

Neurotypical participants inclusion/exclusion criteria:

• No disorder (now or in the past) that could have affected the brain such as cerebrovascular accidents (CVA), neurodegenerative disorders, or essential tremor;

• No neurological diseases that could affect reasoning or intellectual abilities (such as Parkinson's Disease, Epilepsy, and Multiple Sclerosis)

• Neurotypical participants will be matched on age and gender to the ASD population;

ASD participants inclusion/exclusion criteria:

Patients with a formal diagnosis of high-functioning ASD as determined by the clinical psychologist/psychiatrist.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder

Intervention

Device:
• tDCS
Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order

Locations

Country	Name	City	State
Belgium	UZ Brussel	Jette	Brussels

Sponsors (4)

Lead Sponsor	Collaborator
Beatriz Catoira	Universitair Ziekenhuis Brussel, University Ghent, Vrije Universiteit Brussel

Country where clinical trial is conducted

Belgium, 

References & Publications (26)

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Yeung MK, Lee TL, Chan AS. Impaired Recognition of Negative Facial Expressions is Partly Related to Facial Perception Deficits in Adolescents with High-Functioning Autism Spectrum Disorder. J Autism Dev Disord. 2020 May;50(5):1596-1606. doi: 10.1007/s1080 — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Electrical Field Simulations	Simulation of the electric field generated by the tDCS stimulation.	First 10 minutes of assessment
Other	Correlations between DWI, behavioural data, simulation and functional data	The primary outcome measures from the diffusion weighted imaging will provide different measures for structural connectivity per participant. The correlation of these measures with behavioural and/or functional data will be computed.	assessment will include data from the 60 minutes that are spent in the scanner in the session
Primary	PS_RT	Reaction Time in the pictorial sequencing time	assessment will begin 10 minutes after stimulation and last up to 15 minutes
Primary	PS_accuracy	Accuracy in the pictorial sequencing task	assessment will begin 10 minutes after stimulation and last up to 15 minutes
Primary	ER_RT	Reaction Times in the emotion recognition task	assessment will begin 20 minutes after stimulation and last up to 5 minutes
Primary	ER_accuracy	Accuracy in the emotion recognition task	assessment will begin 20 minutes after stimulation and last up to 5 minutes
Primary	Brain activity at the emotion recognition task	Brain activity (fMRI) in regions of interest/whole brain analysis. Differences between stimulation and sham, between task conditions and between sessions as well as possible interactions in between those factors and covariates (AQ scores, age, gender...)	assessment will begin 20 minutes after stimulation and last up to 5 minutes
Primary	Brain activity at resting state	Brain activity (fMRI) in regions of interest/whole brain analysis. Differences between stimulation and sham, between task conditions and between sessions as well as possible interactions in between those factors and covariates (AQ scores, age, gender...)	assesment will begin concurrent with stimulation and last up to 20 minutes
Primary	Brain activity at the pictorial sequencing task	Brain activity (fMRI) in regions of interest/whole brain analysis. Differences between stimulation and sham, between task conditions and between sessions as well as possible interactions in between those factors and covariates (AQ scores, age, gender...)	assessment will begin 10 minutes after stimulation and last up to 15 minutes
Primary	White matter integrity in the cerebellum	White matter integrity matrix (FA, MD, RD) in the cerebellum using tract-based spatial statistics in the cerebellum & differences between groups	assessment will begin immediately after stimulation and last up to 10 minutes
Secondary	Connectivity_PStask	Brain connectivity (fMRI) analysis on the pictorial sequencing task	assessment will begin 10 minutes after stimulation and last up to 15 minutes
Secondary	Connectivity_ERtask	Brain connectivity (fMRI) analysis on the emotion recognition task	assessment will begin 20 minutes after stimulation and last up to 5 minutes
Secondary	Connectivity_stimulation	Brain connectivity (fMRI) analysis during stimulation	assesment will begin concurrent with stimulation and last up to 20 minutes
Secondary	Fiber tractography between the cerebellum and the default mode/ mentalizing network	Fiber tractography (Diffusion weighted imaging) between the cerebellum and the default mode / mentalizing network, by extraction of white matter integrity parameters on each fiber tract	assessment will begin immediately after stimulation and last up to 10 minutes
Secondary	ROI-based structural connectivity	Structural connectivity (DWI) between ROIs from the default mode/mentalizing network	assessment will begin immediately after stimulation and last up to 10 minutes
Secondary	Whole brain structural network construction	Structural connectivity (DWI) within the whole brain using graph theory	assessment will begin immediately after stimulation and last up to 10 minutes