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

Sponsor

Beatriz Catoira (Other)

Overall Status

Recruiting

CT.gov ID

NCT05781412

Collaborator

Vrije Universiteit Brussel (Other), University Ghent (Other), Universitair Ziekenhuis Brussel (Other)

100

Enrollment

Location

Arms

29.2

Anticipated Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder	Device: tDCS	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

There will be three groups of participants: autism-diagnosed, autism-non-diagnosed and neurotypical individuals (healthy controls). On each group, participants will be randomly allocated to one of two groups: anodal stimulation in the first session or anodal stimulation in the second session (in the other session there will be sham stimulation).There will be three groups of participants: autism-diagnosed, autism-non-diagnosed and neurotypical individuals (healthy controls). On each group, participants will be randomly allocated to one of two groups: anodal stimulation in the first session or anodal stimulation in the second session (in the other session there will be sham stimulation).

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

May 24, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Oct 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ASD_anodalstimulation ASD participant, anodal stimulation on the first session, sham stimulation on the second sesion	Device: tDCS Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order
Sham Comparator: ASD_shamstimulation ASD participant, sham stimulation on the first session, anodal stimulation on the second sesion	Device: tDCS Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order
Active Comparator: NT_anodalstimulation Neurotypical participant, anodal stimulation on the first session, sham stimulation on the second sesion	Device: tDCS Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order
Sham Comparator: NT_shamstimulation Neurotypical participant, sham stimulation on the first session, anodal stimulation on the second sesion	Device: tDCS Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order
Active Comparator: H-AQ_anodalstimulation non diagnosed autistic participant,anodal stimulation on the first session, sham stimulation on the second sesion	Device: tDCS Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order
Sham Comparator: H-AQ_shamstimulation non diagnosed autistic participant, sham stimulation on the first session, anodal stimulation on the second sesion	Device: tDCS Anodal and Sham cerebellar tDCS will be used in each participant in a counterbalanced order

Outcome Measures

Primary Outcome Measures

PS_RT [assessment will begin 10 minutes after stimulation and last up to 15 minutes]
Reaction Time in the pictorial sequencing time
PS_accuracy [assessment will begin 10 minutes after stimulation and last up to 15 minutes]
Accuracy in the pictorial sequencing task
ER_RT [assessment will begin 20 minutes after stimulation and last up to 5 minutes]
Reaction Times in the emotion recognition task
ER_accuracy [assessment will begin 20 minutes after stimulation and last up to 5 minutes]
Accuracy in the emotion recognition task
Brain activity at the emotion recognition task [assessment will begin 20 minutes after stimulation and last up to 5 minutes]
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...)
Brain activity at resting state [assesment will begin concurrent with stimulation and last up to 20 minutes]
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...)
Brain activity at the pictorial sequencing task [assessment will begin 10 minutes after stimulation and last up to 15 minutes]
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...)
White matter integrity in the cerebellum [assessment will begin immediately after stimulation and last up to 10 minutes]
White matter integrity matrix (FA, MD, RD) in the cerebellum using tract-based spatial statistics in the cerebellum & differences between groups

Secondary Outcome Measures

Connectivity_PStask [assessment will begin 10 minutes after stimulation and last up to 15 minutes]
Brain connectivity (fMRI) analysis on the pictorial sequencing task
Connectivity_ERtask [assessment will begin 20 minutes after stimulation and last up to 5 minutes]
Brain connectivity (fMRI) analysis on the emotion recognition task
Connectivity_stimulation [assesment will begin concurrent with stimulation and last up to 20 minutes]
Brain connectivity (fMRI) analysis during stimulation
Fiber tractography between the cerebellum and the default mode/ mentalizing network [assessment will begin immediately after stimulation and last up to 10 minutes]
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
ROI-based structural connectivity [assessment will begin immediately after stimulation and last up to 10 minutes]
Structural connectivity (DWI) between ROIs from the default mode/mentalizing network
Whole brain structural network construction [assessment will begin immediately after stimulation and last up to 10 minutes]
Structural connectivity (DWI) within the whole brain using graph theory

Other Outcome Measures

Electrical Field Simulations [First 10 minutes of assessment]
Simulation of the electric field generated by the tDCS stimulation.
Correlations between DWI, behavioural data, simulation and functional data [through study completion]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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;