Verb processing and verb learning in children with paediatric posterior fossa tumours

Survivors of paediatric posterior fossa tumours (PPFTs) often present with
cognitive impairments, and are less likely to finish high school than healthy
peers. Importantly, the amount of words they know (their vocabulary) is related
to their school achievements. Nonetheless, current research typically describes
vocabulary size, while a deeper understanding of language (i.e.
lexical-semantic processing, word learning abilities, and impairments in
learning mechanisms) is crucial for selecting appropriate intervention
strategies.

As verbs are better indicators of everyday language ability than nouns, the
current project characterizes verb processing and verb learning abilities of
children with PPFTs, and compares them to the abilities of typically developing
children (aim 1). In addition, neural correlates of language abilities will be
studied (aim 2), while studying the effects of treatment (surgery,
chemotherapy, and proton therapy) on language ability, as well as the
relationship between changes in language and neuroanatomical changes during and
after the proton therapy treatment (aim 3).

This is an observational study. Children with PPFTs will be tested during the
course of their post-surgical treatment, approximately at 0-2 months, 12
months, and 24 months after surgery. All aspects of the medical treatment
follow standard clinical protocols, without any manipulation related to
participation in the research. It is, therefore, not an intervention study.
However, in the context of this research, children will complete language and
other cognitive assessment tasks at each assessment moment, and the assessment
moments are chosen strategically to observe cognitive and neuroanatomical
changes associated with different moments of the treatment pathway. Regarding
the first timepoint: Given the standard clinical protocols for the different
etiological groups, the post-surgical scan is gathered sometime between 2 weeks
after surgery and not later than 1 week into the RT (normally up to 6 weeks).
The language tests will be administered as early as possible within this
interval.


Additional MRI data will be gathered in UMCG 12 months after surgery. In
addition, routinely gathered neuroimaging data (MRI) and part of the
neuropsychological assessment data collected during the standard clinical
assessments will be shared with the researchers, through data sharing
agreements. A sample of typically developing children, made primarily of
siblings, will also be recruited and act as the control sample. Controls will
be matched in age, gender, and parental education, and will be retested at the
same intervals as patients, in order to support both cross-sectional (for aims
1 and 2) and longitudinal comparisons (for aim 3).

Verb processing and learning ability will be studied in the context of various
levels of syntactic (concerning grammar) and semantic (concerning meaning)
complexity. This will make it possible to identify difficulties with syntax and
semantics and to document their impact on verb learning. We expect children
with PPFTs to experience language impairment and a poor ability to learn new
verbs compared to typically developing peers. Contrasts between children with
children with PPFTs and siblings at 12 to 24 months post surgery will test this
hypothesis, for different aspects of verb learning and verb processing (Aim 1).
We believe that these impairments are associated with structural brain changes
that result from treatment. Hence, relations between brain measures (white
matter integrity, grey matter thickness) and language measure (verb processing
and verb learning) will be studied at 12 months after surgery, to align with
the end of the proton therapy treatment, and children with PPFTs will also be
compared to the healthy siblings in anatomical measures (Aim 2). Finally,
longitudinal changes in anatomical measures and language measures will be
documented during the course of proton therapy (0 months to 12 months after
surgery) and in the year after (12 months to 24 months after surgery), to study
both early and late effects of proton therapy. Across each of these two
12-month periods, the developmental change observed in anatomical and language
measures in children with PPFTs will be compared to corresponding longitudinal
data from healthy siblings (Aim 3).

The testing moments take place 0-2 months, 12 months, and/or 24 months after
surgery. Patients will be required to participate in one session of 1 to 1.5
hours, at one to a maximum of three moments (depending on the moment of
enrollment: see table 1 in the research protocol), followed by an MRI scan
(T1-weighted images and diffusion MRI) at 12 months months after surgery. The
language tests will be planned at the UMCG, at parents* home, or a lab at the
university, as deemed most convenient to the family, after consultation with
parents. There are no expected risks of administering these pen-and-paper or
computer-based tests. However, the child may become tired, or feel unwell
because of the post-surgical treatments that they are undergoing. This way,
each assessment moment will be divided into smaller blocks of 15-30 minutes if
necessary, and assessments will be interrupted flexibly to ensure the child*s
well-being. The remaining measures, including neuropsychological test scores
and MRI data (T1-weighted images and diffusion MRI) will be gathered as part of
standard clinical practice, and shared with the researchers as agreed in data
sharing agreements.

The healthy control group will complete a preliminary screening session of
approximately 1h (to exclude the presence of language impairment), in addition
to the same 1- to 1.5-hour session administered to patients. Both sessions will
be planned in consecutive days, as it is expected that either the researcher or
the participant may have to travel for data collection. Costs will be
reimbursed. Furthermore, siblings will be invited for an MRI session as well,
where the same MRI sequences administered to patients will be gathered. MRI has
no known negative effects on health, and it is a standard brain imaging
technique. There is a risk for individuals with any metal devices in their
body, and these will not be allowed to participate. MRI involves lying still in
a confined environment, which is difficult for children. During acquisition the
scanner makes loud noises. Ear plugs will be provided, but noise is still
audible and can be burdensome. For these reasons, the MRI acquisition will not
be longer than 30 minutes with the session extending up to 1h (including 30
minutes of preparation time). Children and parents will be able to view an
animated cartoon illustrating the procedures of the MRI session and children
will go through a planned playful preparation to minimize any potential worries
related to taking part in MRI acquisition. To minimize boredom, participants
will be allowed to watch a movie during MRI acquisition, since no language
tasks will be administered.

No benefit from participating in this research is anticipated for the healthy
controls. However, their participation enables contrasting the results of
children with PPFTs and identifying aspects of verb processing and verb
learning in which there is evidence of impairment. Such research findings will
potentially provide clinicians with awareness of the need to assess verb
processing and verb learning in this population.

Furthermore, the verb processing and verb learning tests that will be
administered are currently undergoing a standardization process. This way, the
scores of the participants can be contrasted to the normative data and shared
with parents and clinicians, if desired, in the form of a short report. Such
information may be used by the clinicians to help set further directions for
language assessment and intervention for, for example, speech therapists
directly involved in patient care.

Furthermore, this project aims to identify the cortical and subcortical regions
that are at risk of radiation-induced damage, leading to language impairment.
While this information will not be directly beneficial to those taking part in
the present research, it may influence the development of radiation protocols
tailored to spare those regions, and thus improve long-term outcomes and
quality of life of survivors of PPFTs.

Although conducting this research with adults would be easier, posterior fossa
tumors predominantly affect the pediatric population. Furthermore, the
characterization of these children*s language abilities, and linguistic and
neuroanatomical development during the course of post-surgical treatments
cannot be assumed to match the same processes in an adult brain. This way,
findings based on research with adults would not be directly transferable for
the aims of the present research.