To study sensory processing and hyperexcitability in children with ASD and epilepsy using neurophysiological measurements (EEG/ERP).
ID
Source
Brief title
Condition
- Neurological disorders NEC
- Developmental disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: The main outcome parameters are EEG markers: brain evoked P50
suppression, P300, mismatch negativity and absolute resting-state power change.
Secondary outcome
Secondary endpoints: Other EEG phenotypes, neurocognitive and behavioural
parameters.
Background summary
Autism spectrum disorder (ASD) is a behaviorally defined syndrome characterized
by variable abnormalities in social interactions and communication, in
association with restricted interest patterns and unusual stereotyped behaviors
(1). The heterogeneity of ASD has obstructed the development of targeted
treatments. No individual with ASD is the same in terms of clinical
presentation and many different etiological factors have been implicated (2,
3). Nonetheless, preclinical research has revealed the possibility of
converging mechanisms that may contribute to a substantial part of ASD. One
important mechanism is the balance between inhibitory and excitatory inputs in
the brain, also referred to as the E/I balance (4, 5). Many studies in animal
models as well as experimental neurophysiological studies have brought evidence
that an elevated E/I imbalance lead to disturbance in information processing
and functional brain development (6-12). At the same time, it has also been
emphasized that not all forms of ASD might be related to elevated E/I
imbalances and even that the reverse, e.g. excessive inhibition, might also
occur (11, 13). A contribution of hyperexcitable cortical networks, however, is
strongly suggested by the frequent concurrence of epilepsy and/or seizures in
children with ASD (14). Furthermore, the strong aversive reactions of children
with ASD to sensory stimuli further indicates that cortical networks overreact
to relative neutral stimuli (15). Indeed, excessive response to sensory stimuli
is also thought to facilitate or cause seizures (16, 17). Hence, a continuum of
E/I imbalances across ASD and epilepsy is increasingly suggested and may
constitute an important treatment target to reduce excitability and excessive
response to sensory stimuli. In fact, novel treatments are currently being
developed that can lower excitatory (*glutamatergic*) inputs or enhance
inhibitory (*GABAergic*) activity (12). Successful application of these
treatment requires the development of clinical markers that can indicate E/I
imbalances and/or sensory processing deficits. In this study, we aim to deliver
these markers by studying neurophysiological correlates of E/I imbalances in
children with ASD an epilepsy. We hypothesize that the presence of seizure
susceptibility or epilepsy in these types of ASD indicates the presence of
hyperexcitable networks that may be detected by neurophysiological measurements
of resting brain states and sensory processing capabilities.
To test this hypothesis, we will investigate sensory processing in children
with epilepsy and ASD and compare these with typically developing controls and
children with ASD without seizures. Sensory processing and E/I balance
correlates will be assessed using electroencephalography (EEG) and
event-related potentials (ERPs). With these studies we aim to establish
neurophysiological markers of sensory processing deficits and E/I imbalances in
ASD.
Study objective
To study sensory processing and hyperexcitability in children with ASD and
epilepsy using neurophysiological measurements (EEG/ERP).
Study design
Observational study
Study burden and risks
The risks associated with participation in this study are minimal/ negligible.
The burden for the participant is that he or she has to come to the University
medical centre Utrecht three times; for neurocognitive and behavioural
assessments, and for the EEG assessment. The EEG assessment is not an invasive
procedure, although some children might find it uncomfortable to be touched on
the head. In addition to the test days, parents of the participants will be
asked to fill in multiple types of questionnaires about their child. There will
be no direct benefit for the participants. However, in these patients with ASD
and, finding evidence for a E/I imbalance via sensory processing deficits might
give implications for more targeted treatment of (their) behavioural problems
as novel, safe treatments are being developed. Furthermore, this study brings a
detailed characterization of behavioural, sensory and cognitive profile for
each of the participants, which can facilitate better treatment and guidance.
This study will be performed among children with epilepsy and autism as the
aforementioned sensory processing deficits are assumed to cause behavioural
symptoms of hyperexcitability in both disorders. Finding neurophysiological
correlates of sensory processing and E/I deficits might give implications for
better understanding of epilepsy as well as autism, and raises possibilities
for treatment of ASD symptomatology. A typically developing control group is
added to generate reliable reference data.
heidelberglaan 100
Utrecht 3508 GA
NL
heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
Inclusion criteria
Ability to comply with the protocol-specified procedures for the duration of the study
IQ above 70
Written informed consent (and assent if appropriate to local laws and regulations),
In case of methylphenidate use, willingness to skip methylphenidate on the testing days
For epilepsy groups: Males and females aged 7-12, Diagnosis of epilepsy and ASD symptoms (SRS50+ or diagnosis according to ADOS, or probable/definite difference at SP-NLor behavioral problems indicative of sensory processing problems (problems at school, irritability etc)
For ASD group: Males and females aged 7-12, Diagnosis according to ADOS or given by psychiatrist
For control group: Males and females aged 7-15, No psychiatric disorder present
Exclusion criteria
Major visual or auditory impairment
Presence of severe medical disorder
Other (psychiater) disorders other than epilepsy or ASD
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL51700.041.15 |