Section: New Results

Research axis 2: Applications in Neuroradiology and Neurological Disorders

Bimodal EEG-fMRI Neurofeedback for Stroke Rehabilitation: a Case Report

Participants : Giulia Lioi, Mathis Fleury, Simon Butet, Christian Barillot, Isabelle Bonan.

Neurofeedback (NF) consists on training self-regulation of brain activity by providing real-time information about the participant brain function. Few works have shown the potential of NF for stroke rehabilitation however its effectiveness has not been investigated yet. NF approaches are usually based on real-time monitoring of brain activity using a single imaging technique. Recent studies have revealed the potential of combining EEG and fMRI to achieve a more efficient and specific self-regulation. In a case report, we tested the feasibility of applying bimodal EEG-MRI NF on two stroke patients. [54]

This work was done in collaboration with Anatole Lecuyer from the Inria/IRISA HYBRID team.

Refining understanding of working memory buffers through the construct of binding: Evidence from a single case informs theory and clinical practise

Participants : Pierre-Yves Jonin, Quentin Duché.

Binding operations carried out in working memory enable the integration of information from different sources during online performance. While available evidence suggests that working memory may involve distinct binding functions, whether or not they all involve the episodic buffer as a cognitive substrate remains unclear. Similarly, knowledge about the neural underpinnings of working memory buffers is limited, more specifically regarding the involvement of medial temporal lobe structures. In the present study, we report on the case of patient KA, with developmental amnesia and selective damage to the whole hippocampal system. We found that KA was unable to hold shape-colours associations (relational binding) in working memory. In contrast, he could hold integrated coloured shapes (conjunctive binding) in two different tasks. Otherwise, and as expected, KA was impaired on three relational memory tasks thought to depend on the hippocampus that are widely used in the early detection of Alzheimer's disease. Our results emphasized a dissociation between two binding processes within working memory, suggesting that the visuo-spatial sketchpad could support conjunctive binding, and may rely upon a large cortical network including sub-hippocampal structures. By contrast, we found evidence for a selective impairment of relational binding in working memory when the hippocampal system is compromised, suggesting that the long-term memory deficit observed in amnesic patients may be related to impaired short-term relational binding at encoding. Finally, these findings may inform research on the early detection of Alzheimer's disease as the preservation of conjunctive binding in KA is in sharp contrast with the impaired performance demonstrated very early in this disease [15].

This work was done in collaboration with Mario Alfredo Parra and Clara Calia, from Herriot Wyatt University, Edinburgh, UK; with Emmanuel Barbeau and Sophie Muratot from the CNRS 5549 CerCo unit in Toulouse, France; and with Serge Belliard, from CHU de Rennes, Service de Neurologie, Rennes, France.

Superior explicit memory despite severe developmental amnesia: In-depth case study and neural correlates

Participants : Pierre-Yves Jonin, Christian Barillot.

The acquisition of new semantic memories is sometimes preserved in patients with hippocampal amnesia. Robust evidence for this comes from case reports of developmental amnesia suggesting that low-to-normal levels of semantic knowledge can be achieved despite compromised epi-sodic learning. However, it is unclear whether this relative preservation of semantic memory results from normal acquisition and retrieval or from residual episodic memory, combined with effortful repetition. Furthermore, lesion studies have mainly focused on the hippocampus itself, and have seldom reported the state of structures in the extended hippocampal system. Preserved components of this system may therefore mediate residual episodic abilities, contributing to the apparent semantic preservation. We recently reported an in-depth study of Patient KA, a 27-year-old man who had severe hypoxia at birth, in which we carefully explored his residual episodic learning abilities. We used novel speeded recognition paradigms to assess whether KA could explicitly acquire and retrieve new context-free memories. Despite a pattern of very severe amnesia, with a 44-point discrepancy between his intelligence and memory quotients, KA exhibited normal-to-superior levels of knowledge, even under strict time constraints. He also exhibited normal-to-superior recognition memory for new material, again under strict time constraints. Multimodal neuroimaging revealed an unusual pattern of selective atrophy within each component of the extended hippocampal system, contrasting with the preservation of anterior subhippocampal cortices. A cortical thickness analysis yielded a pattern of thinner but also thicker regional cortices, pointing toward specific temporal lobe reorganization following early injury. We thus report the first case of superior explicit learning and memory in a severe case of amnesia, raising important questions about how such knowledge can be acquired [14].

This work was done in collaboration with Emmanuel Barbeau and Gabriel Besson from the CNRS 5549 CerCo unit in Toulouse, France; with Renaud La Joie; with Jérémie Pariente from the Inserm UMR 1214 Tonic unit in Toulouse, France; and with Serge Belliard, from CHU de Rennes, Service de Neurologie, Rennes, France.

Retrieval practice based on recognition memory: testing the retrieval effort hypothesis

Participants : Pierre-Yves Jonin, Christian Barillot.

We tested a core prediction of the retrieval effort hypothesis as an account for the testing effect (TE). Retrieval effort predicts that automatic, effortful retrieval should not lead to TE. Experiment 1 (N=76) showed that despite an encoding duration of three times less, object pictures retention is better after repeated testing under Old/New recognition conditions, than following repeated study. Experiment 2 (N=30) used a speeded and accuracy boosting procedure to rule out the contribution of recollection to retrieval. Retention of object pictures at 25 minutes and 6 months was similar after repeated testing or after repeated studying. These results call for a revision of the retrieval effort hypothesis as a mechanistic account of TE [53].

This work was done in collaboration with Audrey Noël, from Université de Rennes 2, Rennes, France; with Gabriel Besson from the CNRS 5549 CerCo unit in Toulouse, France; with Emmanuel Barbeau and Sophie Muratot from the CNRS 5549 CerCo unit in Toulouse, France; and with Serge Belliard, from CHU de Rennes, Service de Neurologie, Rennes, France.

Voxel-wise Comparison with a-contrario Analysis for Automated Segmentation of Multiple Sclerosis Lesions from Multimodal MRI

Participants : Francesca Galassi, Olivier Commowick, Christian Barillot.

We have introduced a new framework for the automated and un-supervised segmentation of Multiple Sclerosis lesions from multimodal Magnetic Resonance images. It relies on a voxel-wise approach to detect local white matter abnormalities, with an a-contrario analysis, which takes into account local information. First, a voxel-wise comparison of multimodal patient images to a set of controls is performed. Then, region-based probabilities are estimated using an a-contrario approach. Finally, correction for multiple testing is performed. Validation was undertaken on a multi-site clinical dataset of 53 MS patients with various number and volume of lesions. We showed that the proposed framework outperforms the widely used FDR-correction for this type of analysis, particularly for low lesion loads [37].

This work was done in collaboration with Emmanuel Vallée from Orange Labs, Lannion, France.

Integration of Probabilistic Atlas and Graph Cuts for Automated Segmentation of Multiple Sclerosis lesions

Participants : Francesca Galassi, Olivier Commowick, Christian Barillot.

We have proposed a framework for automated segmentation of Multiple Sclerosis (MS) lesions from MR brain images. It integrates a priori tissues and MS lesions information into a Graph-Cuts algorithm for improved segmentation results. [36].

Multiple sclerosis

Spinal Cord

Participants : Anne Kerbrat, Gilles Edan, Jean-Christophe Ferré, Benoit Combès, Olivier Commowick, Élise Bannier, Sudhanya Chatterjee, Haykel Snoussi, Emmanuel Caruyer, Christian Barillot.

The VisAGeS research team has a strong focus on applying the developed methodologies (illustrated in research axis 1) to multiple sclerosis (MS) understanding and the prediction of its evolution. Related to the EMISEP project on spinal cord injury evolution in MS, a first work investigated the magnetization transfer reproducibility across centers in the spinal cord and was accepted for publication [6]. Based on this work, a second work investigated the sensitivity of magnetization transfer to assess diffuse and focal burden in MS patients and was published in Multiple Sclerosis [5].

Reproducibility and Evolution of Diffusion MRI measurements within the Cervical Spinal Cord in Multiple Scleros

Participants : Haykel Snoussi, Anne Kerbrat, Benoit Combès, Olivier Commowick, Élise Bannier, Emmanuel Caruyer, Christian Barillot.

In Multiple Sclerosis (MS), there is a large discrepancy between the clinical observations and how the pathology is exhibited on brain images, this is known as the clinical-radiological paradox (CRP). One of the hypotheses is that the clinical deficit may be more related to the spinal cord damage than the number or location of lesions in the brain. Therefore, investigating how the spinal cord is damaged becomes an acute challenge to better understand and overcome the CRP. Diffusion MRI is known to provide quantitative

figures of neuronal degeneration and axonal loss, in the brain as well as in the spinal cord. In this work, we have proposed to investigate how diffusion MRI metrics vary in the different cervical regions with the progression of the disease. We first study the reproducibility of diffusion MRI on healthy volunteers with a test-retest procedure using both standard diffusion tensor imaging (DTI) and multi-compartment Ball-and-Stick models. Then, based on the test re-test quantitative calibration, we provided quantitative figures of pathology evolution between M0 and M12 in the cervical spine on a set of 31 MS patients, exhibiting how the pathology damage spans in the cervical spinal cord.

Epilepsy

Participants : Élise Bannier, Jean-Christophe Ferré.

Accurate localization of the thalamic subregions is of paramount importance for Deep Brain Stimulation (DBS) planning. Current MRI protocols use T2 and Gadolinium-enhanced T1 images, to visualize both the basal ganglia and the vessels, in order to define the electrode trajectory and target. A study showing the usefulness of Fluid and White Matter Suppression, i.e. FLAWS imaging, in eleven drug-resistant epileptic patients for preoperative Deep Brain Stimulation planning and anterior thalamic nucleus targeting was presented as a Power Pitch at the ISMRM Meeeting in Paris  [27].

This work was done in collaboration with Giulio Gambarota, Anca Nica and Claire Haegelen from the LTSI and Tobias Kober from Lausanne.

Arterial Spin Labeling in pediatric populations

Participants : Élise Bannier, Christian Barillot, Olivier Commowick, Isabelle Corouge, Jean-Christophe Ferré, Antoine Legouhy, Maia Proisy.

Arterial Spin Labeling is an attractive perfusion MRI technique due to its complete non-invasiveness. However it still remains confidential in clinical practice. Over the years, we have developed several applications to evaluate its potential in different contexts. As part of the PhD of Maia Proisy, we have been working on processing and analysing MR perfusion images using arterial spin labeling in neonates and children for several purposes:

• Investigation of brain perfusion evolution between 6 month and 15 years using ASL sequence in order to provide reference values in this age range [4],

• Evaluation of the evolution of the cerebral blood flow changes betwren day-of-life 3 and day-of-life 10 in a population of neonates with hypoxic-ischemic encephalopathy [45], ["Changes in brain perfusion in successive arterial spin labelling MRI scans in neonates with hypoxic-ischaemic encephalopathy", article in revision in Neuroimage: Clinical].

Diffusion MRI in depression

Diffusion MRI as an imaging marker of depression from a large and homogenous population study

Participants : Julie Coloigner, Jean-Marie Batail, Isabelle Corouge, Jean-Christophe Ferre, Christian Barillot.

Despite the extensive therapy options available for depression, up to 80% of patients will suffer from a relapse. Consequently, understanding the neural correlates underlying the depression will optimize the diagnosis and treatment of individual depressed patients. In an experimental study, we investigated alterations of white matter integrity in a large cohort of patients suffering from depression using diffusion tensor imaging. Our findings provide robust evidence that the reduction of white-matter integrity in the interhemispheric connections and fronto-limbic neuronal circuits may play an important role in depression pathogenesis. [34].

This work was done in collaboration with Dominique Drapier from Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France, EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, Rennes, France.

Diffusion MRI as a descriptive imaging marker of the pathogenesis of treatment-resistant depression

Participants : Julie Coloigner, Jean-Marie Batail, Isabelle Corouge, Jean-Christophe Ferre, Christian Barillot.

Despite the extensive therapy options available for depression, treatment-resistant depression (TRD) occurs in 20-30% of depressed patients. Consequently, identification of neural changes in TRD could support to better understand the mechanism of resistance and to improve the treatment of individual depressed patients. We aimed to investigate the white-matter microstructure in a sample of depressed patients in which response to treatment was subsequently evaluated 6 months after. Our findings suggest the abnormalities of the white-matter integrity in multiple white matter tracts, such as anterior limb of internal capsule and genu of corpus may play a role in the pathogenesis of treatment-resistant depression [33].

Depressive disorder is characterized by a profound dysregulation of affect and mood as well as additional abnormalities including cognitive dysfunction, insomnia, fatigue and appetite disturbance. This disease is the most prevalent mental illness, with an estimated lifetime prevalence reported to range from 10% to 15% worldwide. Despite the extensive therapy options available for depression, up to 80% of patients will suffer from a relapse. Consequently, understanding the neural correlates underlying the depression is critical for improving the specificity and efficacy of diagnostic and treatment strategies.Previous studies of structural and functional magnetic resonance imaging have reported several microstructural abnormalities in the prefrontal cortex, anterior cingulate cortex, hippocampus and thalamus. These observations suggest a dysfunction of the circuits connecting frontal and subcortical brain regions, leading to a "disconnection syndrome". Using graph theory-based analysis, we examined white matter changes in the organization of networks in patients suffering from depression. Our diffusion imaging data showed white matter alteration in patients suffering from depression is occurring in the anterior thalamic radiation and in the cingulate bundle. Our findings suggest decreased fiber density in circuits connecting subcortical brain regions with the frontal and parietal cortex, supporting the theory of limbic-frontal circuit dysfunction [50]. We were awarded for this workby the French Institute of Psychiatry for our communication at its annual Forum.

This work was done in collaboration with Dominique Drapier from Academic Psychiatry Department, Centre Hospitalier Guillaume Régnier, Rennes, France, EA 4712 Behavior and Basal Ganglia, CHU Rennes, Rennes 1 University, Rennes, France.