Clinical trial NCT05781412: Modulation of the Activity of the Cerebellum in Autism (MACA)
Official title: Modulation of the Activity in the Cerebellum With Transcranial Direct Current Stimulation in Autistic Participants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: tDCS
Cerebellum
neuromodulation
autism
Lead sponsor: Vrije Universiteit Brussel
Sponsor class: OTHER
Collaborators: name: Vrije Universiteit Brussel
name: University Ghent
name: Universitair Ziekenhuis Brussel
First posted: 2023-03-23
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: PS_RT
timeFrame: assessment will begin 10 minutes after stimulation and last up to 15 minutes
measure: PS_accuracy
timeFrame: assessment will begin 10 minutes after stimulation and last up to 15 minutes
measure: ER_RT
timeFrame: assessment will begin 20 minutes after stimulation and last up to 5 minutes
measure: ER_accuracy
timeFrame: assessment will begin 20 minutes after stimulation and last up to 5 minutes
measure: Brain activity at the emotion recognition task
timeFrame: assessment will begin 20 minutes after stimulation and last up to 5 minutes
measure: Brain activity at resting state
timeFrame: assesment will begin concurrent with stimulation and last up to 20 minutes
measure: Brain activity at the pictorial sequencing task
timeFrame: assessment will begin 10 minutes after stimulation and last up to 15 minutes
measure: White matter integrity in the cerebellum
timeFrame: assessment will begin immediately after stimulation and last up to 10 minutes
Secondary outcomes:
measure: Connectivity_PStask
timeFrame: assessment will begin 10 minutes after stimulation and last up to 15 minutes
measure: Connectivity_ERtask
timeFrame: assessment will begin 20 minutes after stimulation and last up to 5 minutes
measure: Connectivity_stimulation
timeFrame: assesment will begin concurrent with stimulation and last up to 20 minutes
measure: Fiber tractography between the cerebellum and the default mode/ mentalizing network
timeFrame: assessment will begin immediately after stimulation and last up to 10 minutes
measure: ROI-based structural connectivity
timeFrame: assessment will begin immediately after stimulation and last up to 10 minutes
measure: Whole brain structural network construction
timeFrame: assessment will begin immediately after stimulation and last up to 10 minutes
Other outcomes:
measure: Electrical Field Simulations
timeFrame: First 10 minutes of assessment
measure: Correlations between DWI, behavioural data, simulation and functional data
timeFrame: assessment will include data from the 60 minutes that are spent in the scanner in the session
Locations:
city: Jette
country: Belgium
facility: UZ Brussel
state: Brussels
Study officials:
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