In line with our previous works, the goal is now (1) to better study the neural basis underlying these mechanisms of plasticity, with especially an improvement of the knowledge of the cerebral connectivity (2) to analyze the role of the normal and tumoral human stem cells in central nervous system remapping.

One project is to perform anatomical dissections of the white matter pathways in the laboratory of anatomy (PhD Thesis Igor Maldonaldo).

Duffau Img1Example of anatomic dissection of the inferior fronto-occipital fascicle – from Martino et al., Cortex 2010.

 

 

 

 

 

The complementary study is based on the use of diffusion tensor imaging, which enables the tracking of subcortical white bundles, and to combine these new findings to functional MRI (PhD Thesis Nicolas Menjot) in collaboration with the department of Neuroradiology of Pr. Alain Bonafé (CHU Montpellier).

Duffau Img2

Example of tracking of the white matter pathways in human, showing the relationships between the arcuate fascicle (blue), the middle longitudinal fascicle (red), the inferior fronto-occipital fascicle (yellow) and the inferior longitudinal fascicle (green) – from Menjot et al.

 

 

 

 

Secondly, our aim is also to improve the sensitivity of the cognitive tasks performed intraoperatively during awake surgery of glioma in eloquent areas, by using direct electrical stimulation mapping. The goal is to optimize the accuracy of the on-line anatomo-functional correlations, both at cortical and subcortical levels. Indeed, we have extensively shown that intrasurgical mapping under local anesthesia allowed the optimization of the benefit-to-risk ratio of glioma surgery, i.e. to maximize the extent of resection while minimizing the risk of permanent deficit. However, preservation of the quality of life on the basis of the better understanding of dynamic processing of brain connectivity and plasticity is possible only if the functional tests are adapted to each patient. This is the reason why we will also better examine the patients before and after surgery from a neuropsychological point of view, especially regarding semantic processing and executive functions (PhD Thesis Sylvie Moritz-Gasser) as well as emotions, behavior and consciousness (PhD Thesis Guillaume Herbet). To this end, in addition to the visual input frequently used in our past experience, it is important to incorporate more systematically the auditory input, with the aim to (1) move towards a multimodal (auditivo-verbal) assessment and mapping of the patients (2) to discriminate the impact of possible deficit of auditory processing in cognitive function such as working memory and attentional processing (3) to improve the knowledge of the neural foundations sub-serving higher integrative functions. We would also like to create new programs of functional rehabilitation adapted to each patient.

Duffau Img3   Duffau Img4bCorrelation between intraoperative electrostimulation and tractography with regard to spatial cognition – from Thiebaut de Schotten et al., Science 2005.

 

 

 

 

Furthermore, brain remapping will be longitudinally studied, using non-invasive functional neuroimaging before and after surgery for glial tumors, combined to intraoperative electrical mapping at cortical and subcortical levels. Moreover, in cases of re-operation some years later, the same paradigm will be used to analyze functional redistribution in the same patient over time, and to define an “individual index of plasticity” useful both for basic neuroscience and for the therapeutic management, i.e. preservation of the quality of life. The ultimate goal is to revisit the classical models of anatomo-functional connectivity, i.e. to move from a localisationist concept to a “hodological” view of brain organization.

Duffau Img4   Duffau Img5   Duffau Img6Different patterns of brain reorganization in patients without deficit harboring a low-grade glioma involving the left dominant insula: intralesional (left), perilesional (middle) and contralesional (right) activations during language functional MRI – from Duffau, Lancet Neurol 2005.

 

Finally, we would like to make a link between cognition, functional anatomy, and ultrastructural mechanisms of brain plasticity. We propose to study the role of the normal human stem cells in central nervous system remapping. Indeed, we have the possibility to obtain samples from the subventricular zone, white and grey matter of the encephalon, during cerebral surgery, especially for surgical approaches within the normal brain (H Duffau/L Bauchet). The study of normal stem cells is carried by JP Hugnot, in strong collaboration with group 2. This last point is crucial to compare normal and tumor stem cells.

 

Major publications

Almairac F et al., Neurology. In press
Duffau H, Neurology. In press
Herbet G et al., Neurology. Feb 14. [Epub ahead of print], 2018
Bourdillon P et al., Epilepsia. 58:2038-2047, 2017
Herbet G et al., Brain. Mar;139(Pt 3):829-44, 2016
Herbet G et al., Brain. 139:3007-3021, 2016
Herbet G et al., Brain. 139:e23, 2016
Duffau H, Taillandier L, Neuro Oncol. 17:332-342, 2015
Surbeck W et al., Neuro Oncol. 17:574-9, 2015
Duffau H, Nat Rev Neurol. May;11(5):255-65, 2015

 

Collaborations

  • University of Amsterdam (Netherlands)
  • University of Califormia San Francisco (USA)
  • University of Chicago (USA)
  • University of Osaka (Japan)
  • University of Madrid (Spain)
  • University of Basel (Switzerland)
  • University of Natal (Brazil)
  • University of Roma (Italy)
  • University of Guangzhou (China)

 

Fundings

AOI 2010
PHRI 2011

 

Contact

Duffau Hugues