Fractioning the phenotype of the biology of the visual Conscious networks. – Phenotypes

We employed various approaches to measure the brain connectivity in healthy controls and brain disconnection in patients.
We setup advanced magnetic resonance sequences to quantify the strength of the white matter connections (functional connectivity between the projections), their myelination (T1/T2 ratio) as well as their density (hindrance modulated orientational anisotropy). These measures will be correlated to original measures of conscious perception in healthy controls and patients. We developed a new software suite, the BCBtoolkit available freely at the following link www.brainconnectivitybehaviour.eu. BCBtoolkit allows for advanced measure of white matter connections in patients with a brain damage

For the first time, we mapped new white matter connections in the human brain (Rojkova et al. 2015), applied this new knowledge through the use of our software to the evaluation of the recovery of patients with a brain damage in the left (Forkel et al. 2014) and the right side of the brain (Lunven et al. 2015) as well as in keystone neurological patients (Thiebaut de Schotten et al. 2015). Our main conclusion is that the disruption of white matter pathways is the main denominator for most of the disfunctioning of the damaged human brain and consequently the functioning of the healthy human brain.

We are now tackling the core part of the project, which is to identify different white matter phenotypes within the healthy population and to relate these phenotypes to different brain functioning. We are currently analyzing data acquired from 35 healthy volunteers and we are starting to collect high-resolution longitudinal data from patients with a stroke in the right hemisphere.

We produced 8 papers in good journals (impact factor > 5), submitted 5 additional papers, released a new analysis software (BCBtoolkit, www.brainconnectivitybehaviour.eu) and obtained two prizes (Elisabeth Warrington www.the-bns.org and Cortex www.fesn.eu Prizes).

From spotting a friend in the crowd to avoiding a potential threat, we crucially depend on the proper access of visual information to our consciousness. However, in some neurological conditions, this access may be stopped, which severely and negatively affects the quality of life for thousands of individuals. For instance, following 80% of strokes in the right hemisphere, a group of common disorders of visual conscious access frequently occur, leading to debilitating neuropsychological symptoms such as, hemineglect. Hemineglect patients seem to live in a halved world; they do not eat from the left part of their dish, or see obstacles situated on their left side, but more importantly, hemineglect presents several dangers to everyday life, including increasing the risk for car accidents and severe falls. Currently, only 40% of patients with hemineglect will eventually recover within 6 months. This means that 480,000 new European patients every year will remain symptomatic, which spoils their quality of life and prevents them from returning to work. Early identification of simple anatomical predictors of visual conscious access recovery may significantly reduce the burden of the disorder on the individuals, their families and society at large, and will lead to the discovery of new treatment tractable targets.

Although a fronto-parietal cortical network for visual conscious experience has previously been described, progress has been hampered by the inability to visualise white matter connections supporting this in vivo network. During my post-doctorate at King’s College London I have pioneered the development of advanced non-invasive magnetic resonance imaging (MRI) techniques that allows for the reconstruction fronto-parietal pathways in the living human brain. With these tools, I wish to define the anatomical connectivity and uncover the dynamic characteristics of the conscious network in the living human brain, using state-of-the-art methodologies.

To do this, I propose two main objectives: i) Define the biology of the healthy human visual conscious network in an integrated way in order to fractionate its phenotype ii) Find the biomarkers that are associated with predispositions to recover from hemineglect.
Three different, but complimentary connectivity measures will be used to achieve the project’s objectives. Advanced diffusion imaging and tractography will be applied to reconstruct the anatomical connections of the network and characterise their white matter microstructure properties (e.g. axonal density and diameters). Multi-component and multi-compartmental MR relativity analysis will be used to quantify T1, T2 and extract an index of myelination for the brain connections. Additionally, measures of effective connectivity (e.g. dynamic causal modeling DCM) using functional magnetic resonance imaging (fMRI) will finally offer a dynamic picture of the network that supports visual conscious access in healthy and pathological brains.

If successful these first studies will allow me to determine if measures of brain ‘connectivity’ can translate into advanced standard operating procedures for more personalised medicine by aiding clinical diagnosis, and helping predict symptom changes of individuals.