Intervention induced reconfiguration of functional brain networks in dyslexic readers

The study is set up against the background of three emerging theoretical fields
in neuroscience: complex network analysis of brain activity, the brain as part
of a complex dynamical system (brain-body-environment system) and the analysis
of resting state brain activity. Related to developmental dyslexia the
following

1. Variability in repeated measures of cognitive performance in developmental
dyslexia are indicative of impaired coordination dynamics at the micro-scale
level of emergent (neuro-)physiological synchronization.

2. A wide range of structural anomalies in the organization of brain networks
have been associated with developmental dyslexia. Intervention induced changes
in structural connectivity have been reported.

3. A wide range of functional anomalies in patterns of activation of brain
networks have been associated with developmental dyslexia. Intervention induced
changes in functional connectivity have been reported.

4. Synchronization and coordination of physiological processes in body and
brain have been shown to develop naturally from independent component dynamics
towards interdependent scale-free, interaction dominant dynamics. Such dynamics
signify health and wellbeing of body and mind, fuency and proficiency of
(cognitive) performance. Change towards metastable dynamics can be induced by
means of medical and behavioural intervention. Change away from metastable
dynamics can be induced by disease and constraints of structural system
organization and the environment.

5. Studying the changes in structural and functional complex brain networks
induced by an intervention program known to cause behavioural changes in
developmental dyslexia allows for the study of micro-to-macro scale emergence
of behavior, as well as the macro-to-micro constraining of structural and
functional networks induced by an intervention program: An inquiry into
learning and plasticity.


The three major hypotheses derived from the framework above are:

1. Based on results obtained in our fuency and dispersion studies of impaired
reading: Complex networks obtained from resting-state activity of dyslexic
readers should show deviations from scale-free network organization.

2. Based on our studies showing that practice improves emergent coordination
dynamics: Within subject comparison of measurement occasions should reveal
network reconfiguration associated to behavioural improvement.

3. Based on our studies showing trade-offs across multiple scales of
coordination that depend on low-level principles of energy minimisation and
high-level task constraints: A hierarchy of connectivity changes associated
with component processes of reading is expected with processes demanding
highest integration and coupling between components to be the most resistant to
change.

1. Quantify changes in structural and functional brain networks within dyslexic
readers, induced by an intervention with known and established behavioural
effects.

2. Examine whether short brain activity acquisition (5-8 minutes) of the
resting state can reveal structural differences between dyslexic and average
readers.

3. Examine whether a characterisation of the structure*function interaction or
coupling of such networks within dyslexic readers provides insight into
differences in resistance to intervention between dyslexic readers.

4. Examine bi-directional association of micro-scale changes in brain networks
to macro-scale behavioural changes.

Three groups of 15 participants aged 10-12 years of age, will take part in the
study:

1. ListEnter: Clients who enter the waiting-list, that have just been diagnosed
with developmental dyslexia.
2. ListLeave: Clients who are leaving the waiting-list and are about to start
the intervention program.
3. Classroom: A control group of children sampled from the classrooms of the
participants diagnosed with developmental dyslexia.

All groups (total N=45) will be measured at least three times, the ListLeave
group ideally start the first measurement within the same month as the
ListEnter group and thus serves as a natural *no-intervention* control group to
the ListLeave group. As soon as a client in the ListEnter group leaves the
waiting-list to start the intervention program, their second measurement will
be performed.



Records of brain activity will be acquired using Magneto Encephalo Graphy
(MEG). After each measurement occasion a structural image will be acquired (for
co-registration purposes), using Magnetic Resonance Imaging (MRI). This is
warranted by the developing brains of the young participants in this study.

Structure: Resting-state
Analysis of resting state brain-activity enabled a majority of the reported
complex brain network studies to distinguish between experimental groups
(hypothesis 1). The proposed design allows for the first time assessment of
within subject structural changes induced by intervention (hypothesis 2).
Acquisition of resting-state activity is straightforward and involves the
participant closing his or her eyes for 5 to 8 minutes. The present study will
sample resting-state MEG at the beginning of each experimental session, at all
three measurement occasions. Additionally, a functional
MRI resting state will be acquired. This involves little additional burden, as
it can be obtained after acquisition of the structural MRI and does not involve
any activity on behalf of the participant. These measurements will be used to
analyze the structural brain connectivity with greater spatial resolution than
that of MEG. MEG on the other hand has superior temporal resolution allowing
for accurate analysis of functional connectivity.

Function ~ Behaviour: Phonology, reading and spelling
Recent studies of complex brain networks compare qualitatively different states
of activity, or associate cognitive performance to resting-state network
characteristics. The proposed study will do both in that resting-state network
characteristics will be associated with behavioural measures recorded during
diagnosis and various stages of the intervention. Additionally, measurements of
four important component processes that are also part of differential diagnosis
and progress assessment. These are the reading of a short story; the reading of
words and pseudo words; letter-sound identification and speech sound
manipulation by deletion. Each task will be performed inside the MEG scanner
and takes about 5 minutes to complete. The tasks have been adapted to enable
performance during brain activity acquisition and require a button press, or no
response at all.
The total duration of the experiment amounts to less than 30 minutes in the
MEG, followed by a 10 minute MRI scan to acquire a structural volume and
functional resting-state measurements.

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