Relationship between large-scale structural and functional brain connectivity in the human lifespan
Creators: name: TOSELLI, BENEDETTA
Publisher: name: Universit� degli studi di Genova
Year: 2019

description: The relationship between the anatomical structure of the brain and its functional organization
is not straightforward and has not been elucidated yet, despite the growing interest this topic
has received in the last decade. In particular, a new area of research has been defined in these
years, called ?connectomics?: this is the study of the different kinds of ?connections? existing
among micro- and macro-areas of the brain, from structural connectivity ? described by
white matter fibre tracts physically linking cortical areas ? to functional connectivity ?
defined as temporal correlation between electrical activity of different brain regions ? to
effective connectivity?defining causal relationships between functional activity of different
brain areas. Cortical areas of the brain physically linked by tracts of white matter fibres
are known to exhibit a more coherent functional synchronization than areas which are not
anatomically linked, but the absence of physical links between two areas does not imply a
similar absence of functional correspondence. Development and ageing, but also structural
modifications brought on by malformations or pathology, can modify the relation between
structure and function.
The aim of my PhD work has been to further investigate the existing relationship between
structural and functional connectivity in the human brain at different ages of the human
lifespan, in particular in healthy adults and both healthy and pathological neonates and
children. These two ?categories? of subjects are very different in terms of the analysis
techniques which can be applied for their study, due to the different characteristics of the data
obtainable from them: in particular, while healthy adult data can be studied with the most
advanced state-of-the-art methods, paediatric and neonatal subjects pose hard constraints to
the acquisition methods applicable, and thus to the quality of the data which can be analysed.
During this PhD I have studied this relation in healthy adult subjects by comparing structural
connectivity from DWI data with functional connectivity from stereo-EEG recordings
of epileptic patients implanted with intra-cerebral electrodes. I have then focused on the
paediatric age, and in particular on the challenges posed by the paediatric clinical environment
to the analysis of structural connectivity. In collaboration with the Neuroradiology
Unit of the Giannina Gaslini Hospital in Genova, I have adapted and tested advanced DWI analysis methods for neonatal and paediatric data, which is commonly studied with less
effective methods. We applied the same methods to the study of the effects of a specific brain
malformation on the structural connectivity in 5 paediatric patients.
While diffusion weighted imaging (DWI) is recognised as the best method to compute
structural connectivity in the human brain, the most common methods for estimating functional
connectivity data ? functional MRI (fMRI) and electroencephalography (EEG) ?
suffer from different limitations: fMRI has good spatial resolution but low temporal resolution,
while EEG has a better temporal resolution but the localisation of each signal?s
originating area is difficult and not always precise. Stereo-EEG (SEEG) combines strong
spatial and temporal resolution with a high signal-to-noise ratio and allows to identify the
source of each signal with precision, but is not used for studies on healthy subjects because
of its invasiveness.
Functional connectivity in children can be computed with either fMRI, EEG or SEEG,
as in adult subjects. On the other hand, the study of structural connectivity in the paediatric
age is met with obstacles posed by the specificity of this data, especially for the application
of the advanced DWI analysis techniques commonly used in the adult age. Moreover, the
clinical environment introduces even more constraints on the quality of the available data,
both in children and adults, further limiting the possibility of applying advanced analysis
methods for the investigation of connectivity in the paediatric age.
Our results on adult subjects showed a positive correlation between structural and functional
connectivity at different granularity levels, from global networks to community structures
to single nodes, suggesting a correspondence between structural and functional organization
which is maintained at different aggregation levels of brain units. In neonatal and
paediatric subjects, we successfully adapted and applied the same advanced DWI analysis
method used for the investigation in adults, obtaining white matter reconstructions more
precise and anatomically plausible than with methods commonly used in paediatric clinical
environments, and we were able to study the effects of a specific type of brain malformation
on structural connectivity, explaining the different physical and functional manifestation
of this malformation with respect to similar pathologies. This work further elucidates the
relationship between structural and functional connectivity in the adult subject, and poses
the basis for a corresponding work in the neonatal and paediatric subject in the clinical
environment, allowing to study structural connectivity in the healthy and pathological child
with clinical data.