Commonalities in visual perception between children at familial risk for synaesthesia and in children with autism spectrum disorder

It recently became known that people with autism spectrum disorder (ASD) are at
least five times more likely (20%) than healthy controls (2-4%) to have a form
of synaesthesia, a mixing of the senses (e.g. seeing colours for letters). In
the DSM-5, alterations in sensory processing are part of the diagnostic
criteria for ASD and sensory dysregulation in ASD is regarded as a very
important topic in the ASD literature at the moment (Green et al ). Synesthesia
is part of the sensory dysregulation occurring in ASD and can provide important
information on how sensory processing is dysregulated in ASD patients. Linking
ASD and synaesthesia may inspire new perspectives on the neurobiological
mechanisms underlying ASD. Investigating synaesthesia in relation to other
sensory abnormalities in ASD patients will enhance our understanding of sensory
dysregulation in ASD.
In ASD, detail perception is enhanced compared to global
structure/motion processing. We aim to show the same imbalance in children who
are likely to develop synaesthesia (since synaesthesia is heritable (~40%),
children of whom one parent has synaesthesia are likely to develop the
condition). We specifically test the hypothesis that early changes in visual
sensory processing occur in both synaesthetessia and ASD patients and are
related to the presence of synaesthesia. To this end, 4-5 year old children
will watch static grating stimuli of high (detail) and low (global structure)
spatial frequency while we measure electrophysiological activity of the brain
using EEG. We will investigate children prior to the emergence of
grapheme-colour synaesthesia, excluding synaesthesia itself as the cause of
altered visual processing. We conduct a longitudinal follow-up test for the
actual emergence of synaesthesia (expected: 40% in potential synaesthete group,
20% in ASD group) and compare the experimental outcomes of participants with
and without synaesthesia.

Primary objective:
To assess whether synaesthesia and ASD lead to similar alterations in
electrophysiological brain activity during visual information processing,
expressing a bias towards detail/high spatial frequency information processing
in the visual system.

Secondary objectives:
1) shedding more light on the co-occurrence of visual abnormalities and
synaesthesia in young ASD patients;
2) assessing the presence of synaesthesia in ~5 year olds with and without ASD;
3) assessing group differences on other aspects: visual prospective memory
abilities, reading abilities, scores on screening questionnaires, chromatic
stimulus processing.

A between-subjects study with three groups.
The between-subjects comparison is combined with a cohort-study, in which
longitudinal outcomes will be related to initial (physiological and
behavioural) characteristics.

Sessions:
- ADOS diagnostic test for the ASD group
- Eelectroencephalography (EEG) (age 4/5)
- Questionnaires by parents and synaesthesia test by children aged 4/5
- Follow-up reading tasks and synaesthesia test (age 6/7)

The study bears no risks for the participants, since all the experimental
measures are either behavioural tests or completely safe non-invasive tests.
The nature and extent of the burden for the participants, and the group
relatedness are described in detail in Chapter 11.4 of the Research protocol.
Below is a summary of this chapter.

With regard to the burden for the participants:

The study comprises the following sessions.
- ADOS diagnostic test for the ASD group
- Eelectroencephalography (EEG) (age 4/5)
- Questionnaires by parents and synaesthesia test by children aged 4/5
- Follow-up reading tasks and synaesthesia test (age 6/7)

The burden for participants consists of a time investment of 3 to 4 hours and
the efforts and discomforts that come with taking part. We expect only the EEG
session during the lab visit to possibly cause discomfort in the sense of
stress for the young participants, since this session will take place in a new
environment, while all other tasks will be done either from the children*s home
or at the children*s regular treatment centre (ADOS). We expect that possible
stress and discomfort will be mainly experienced in the ASD group. Karakter
University Centre has a lot of experience in running experiments with young
children with ASS and with preparing children for the experiments. We will do
our utmost best to make the visit to our lab as safe, comfortable, and
predictable as possible to minimize the risk of stress and discomfort. Our
procedures are described in detail in Chapters 8.3 and 11.4 in the Research
Protocol. We will apply the following measures for the ASD patients.
Children with ASD will receive an example EEG cap to take home in order
to familiarize themselves with the feel and look of the cap (at least one week
prior to the lab visit). When handing out the cap parents will be instructed
how the cap will be placed on the child*s head during the procedure and that it
might be necessary to also touch the child*s head during the application of
additional gel in the electrodes, so that this can be practiced at home as
well. Children will be given photos of the site of the lab visit, including
photographs of the building*s exterior entrance, interior entrance, the
hallway, the entrance to the laboratory, the main area of the laboratory, and
the EEG cabinet. This will help them to prepare for their visit. Again, parents
will be informed during the telephone interview which procedures will take
place during the experiment and will be asked what their child*s possible
reactions may be, and will be asked what kind of toy materials might distract
the child the best during EEG preparation.
For non-ASD participants, the preparation procedure will be the same
except for the EEG cap, which will not be provided physically prior to the
experiment but only in the form of a photograph (in the information letter).
Tthe EEG preparation will be done by experienced researchers who can
apply the cap quickly and with minimal discomfort for the children. The study
will be run in a very child-friendly EEG-lab that is specifically used and
equipped for infant and child EEG-studies. Toys are available and the lab is
spacious and bright. In a large-scale study in babies, the EEG-measurements are
taking place without problems in this new environment for the babies. The
experimenters will be trained and experienced in conducting research with young
children. At all times, prior to and during the study, the children will be
clearly informed about the next steps in the experiment so that they know what
to expect and are prepared. This is especially relevant for the children with
ASD. The child*s caregiver will remain with the child at all times during the
experiment and where possible, the child will be allowed to sit on the
caregiver*s lap if that is desired. After every step in the EEG cap application
(putting it on the head, adjusting the chin strap or harness, and electrode
preparation) the child will be rewarded with a toy or colouring in of an EEG
diploma. The EEG session during the lab visit will be kept as short as possible
(therefore we use a passive viewing paradigm, in which trial time can be
short).


Group relatedness

There are three main reasons why the study is group related with respect to the
age of the children.

First of all, a research goal is to gain knowledge about abnormalities in the
development of the visual sensory system at a young age in the ASD population.
Sensory dysregulation is included as a diagnostic criterium of ASD in the
recent DSM-5, and this research topic is regarded as very important in the
current ASD research field. There is a growing hypothesis that many symptoms in
ASD that are related to higher cognition may originate from altered sensory
processing at a very basic level. Synaesthesia is a manifestation of altered
perceptual processes in ASD and may serve as a model condition to investigate
sensory dysregulation. It is expected that more knowledge about sensory
dysregulation, sensory symptoms and their relation to early
electrophysiological markers of brain development, and later clinical outcomes
will lead to important clinical benefits for ASD patients: 1) More knowledge
about sensory dysregulation in young children can possibly lead to altered and
earlier interventions in ASD patients; 2) More knowledge can lead to more
fine-tuned care for patients: if we can establish that ASD patients with
synaesthesia benefit more or less from their current treatments than patients
without synaesthesia, synaesthesia in ASD may function as a biomarker for ASD
subtypes (we expect 20% of our ASD participants to develop synaesthesia); 3)
Better ASD diagnostics. These clinical benefits are described in detail on page
12/13 of the Research protocol as well as in Chapter 11.4.
If we want to understand the early development of ASD symptoms better,
in order to facilitate earlier interventions and better treatments, we have to
investigate sensory perception at a young age as well. This is why we intend to
perform this study with young children. We want to emphasize that our
integrated approach, including physiological as well as behavioural tests, and
a follow-up session, will also be very useful in the clinical sense for the
individual participants in the study.

The second reason for performing this study with young children is that there
is a very limited amount of brain research available on visual information
processing in children of this age with ASD. Out study will therefore have
great additional value for the field.

A third reason for investigating children specifically at age 4/5 is that for
the synaesthesia and ASD groups, we expect visual perception to be altered
prior to the development of synaesthesia. Only by testing children before they
develop synaesthesia can we test this hypothesis. This is why we intend to test
children at an age where they are usually not able to recognize letters in an
automatic fashion (before entering or just after entering group 2 in the Dutch
primary school system).