Clément Debacker

Anorexia nervosa (AN) is a severe psychiatric disorder with high relapse rates despite successful weight restoration. Altered reward processing and an imbalance between goal-directed and habitual control within the striatum have been proposed to contribute to the persistence of maladaptive behaviours, but the striatal mechanisms underlying recovery and relapse remain unclear. Here, we combined cross-species structural MRI, including cross-sectional analyses in mice and longitudinal neuroimaging and clinical assessments in patients with AN, to investigate striatal alterations associated with recovery. Male mice with deletion of the vesicular acetylcholine transporter (VAChTcKO; n = 9), a model of maladaptive eating behaviour, showed reduced dorsolateral striatal volume compared with wild-type mice (n=9). At baseline, women with AN (n = 71) showed reduced striatal volumes compared with healthy controls (n = 30). Longitudinally, patients with AN (n = 41) and healthy controls (n = 28) were reassessed, revealing substantial recovery of striatal volumes following weight restoration in AN. Posterior-anterior putamen gradient changes differed according to subsequent remission status, with changes in the right putamen gradient predicting relapse. Striatal gradient changes were also associated with goal-directed and habitual behaviour during the slip-of-action task, response consistency during delay discounting, and circulating ghrelin and desacyl ghrelin concentrations. These findings identify longitudinal putamen reorganization as a candidate marker of vulnerability to relapse and link striatal plasticity, goal-directed and habitual control, reward processing, and metabolic processes in AN.

Background: Major Depressive Disorder is highly prevalent, and approximately 30% of patients develop treatment-resistant depression (TRD). Electroconvulsive therapy (ECT) remains the most effective treatment for TRD. Given the central role of the subcallosal cingulate (SCC) in depression, we investigated whether baseline SCC functional connectivity predicts ECT response and whether default mode network (DMN) connectivity changes are associated with clinical improvement.Methods: In this longitudinal study, 47 patients with TRD undergoing ECT and 25 matched healthy controls (HC) were recruited. Usable resting-state fMRI were available for 30 patients and 22 HC. Depression severity (Montgomery–Åsberg Depression Rating Scale, MADRS) and rs-fMRI were assessed at baseline, after five ECT sessions, and at the end of treatment. SCC functional connectivity was investigated using seed-based and region-of-interest analyses.Results: ECT was associated with a reduced SCC-medial prefrontal cortex connectivity, a core DMN region (pFDR = 0.001). Higher baseline SCC connectivity with a left prefrontal cluster (MNI:–22, 28, 28) was associated with greater clinical improvement (r = 0.59; p = 0.002). This connectivity was positive in remitters, negative in non-remitters, and near zero in HC. Complementary network-level analyses further identified baseline differences between remitters and non-remitters within a PCC-centered DMN subnetwork.Conclusion: SCC- and DMN-related connectivity patterns were associated with ECT responsiveness. The opposite baseline SCC connectivity observed in remitters and non-remitters suggests distinct functional network states linked to treatment outcome. If replicated, these findings may support the development of biomarker-guided neuromodulation strategies aimed at optimizing response to ECT.

A large MRI voxel-based atlas mapped intracranial meningioma distributions, linking location to symptoms, management, and malignancy grade, and provided a standardized spatial reference to anticipate presentation and guide clinical decision-making.

Ce travail de thèse, principalement méthodologique, s'est intéressé aux techniques d'imagerie par résonance magnétique (IRM) permettant de mesurer le flux sanguin cérébral (CBF) et plus particulièrement aux techniques de marquage de spins artériels (ASL), qui utilisent les protons de l'eau du sang comme marqueur. Nous avons mis en place la séquence ASL de marquage pseudo-continu (pCASL) et évalué sa réponse à un stimulus hypercapnique. Nous avons évalué différentes stratégies pour optimiser l'efficacité d'inversion. Pour cela, nous avons également mis en place des outils de simulations numériques des approches ASL. Nos résultats démontrent que l'efficacité d'inversion est influencée par l'homogénéité du champ magnétique dans la région de marquage, ce qui pose un problème à haut champ magnétique. Le protocole pCASL optimisé a ensuite été évalué chez le rat à trois champ magnétiques (4.7, 7, et 11.7T) et comparé avec une approche en ASL continu classique (CASL). Cette comparaison a montré une excellente reproductibilité inter-animal et inter-champ de la méthode développée. Dans une seconde partie, nous nous sommes également intéressés à l'influence du temps de relaxation longitudinal (T1) du tissu cérébral sur les valeurs du CBF calculées. Pour cela, nous avons modifié le T1 du tissu par une injection intra-cérébrale de manganèse. Cette étude a montré la difficulté de prendre en compte le changement de T1 du tissu. Dans une troisième partie, nous avons évalué l'apport d'une antenne de marquage spécifique pour l'approche CASL en comparant les mesures de CBF obtenues avec celles de la pCASL. Nous avons observé une bonne concordance entre ces deux méthodes à travers les coupes. Nos résultats illustrent également l'importante contribution du transfert d'aimantation dans les séquences de CASL. Les outils développés au cours de cette thèse sont en cours d'application dans des protocoles d'étude de modèles de tumeurs cérébrales, d'accident vasculaire cérébral et de traumatisme crânien.

Background Correlating the human connectome with clinical responses elicited during intraoperative brain mapping helps understanding of the intrinsic organization of the human brain. Methods for locating eloquent sites on neuroimaging are not standardized. In the present study, we standardized a methodology for locating subcortical eloquent sites identified during intraoperative mapping for awake brain tumor resection on a reference brain template. Methods Subcortical eloquent sites were tagged by co-registration of intraoperative photographs with early postoperative MRI ( < 48 h). Neuroimaging data were normalized into MNI152 space. To assess whether the location of subcortical eloquent sites on the MNI template was concordant with the expected brain connectivity, we compared each subcortical eloquent site with the Human Connectome Project 1065 probabilistic tractography atlas. Results We analyze 290 subcortical eloquent sites identified during 69/90 awake surgeries. 2/290 (0.7%) subcortical eloquent sites identified intraoperatively do not intersect with a fiber tract according to the reference atlas. Among the other 288 that successfully intersect with, at least, one white matter tract, 255/288 (88.5%) have a clinical response elicited intraoperatively that is congruent with the intersected white matter tract. In the remaining 33/288 (11.5%) functional incongruent and the 2/290 (0.7%) anatomical incongruent subcortical sites, the minimal mean distance between the eloquent site and a congruent with matter tract is 3.6 ± 4.4 mm (range 1.0–23.9, median 3.6, interquartile range 2.5–5.4). Conclusions We propose a standardized methodology to locate with accuracy on a reference brain template subcortical eloquent sites identified intraoperatively during functional brain mapping using direct electrical stimulations under awake condition.

Electroconvulsive therapy (ECT) induces hippocampal volume increases in depressed patients, potentially reflecting neuroplasticity. We hypothesized that Neurite Orientation Dispersion and Density Imaging (NODDI) could provide in vivo evidence of hippocampal neuroplasticity following ECT. This longitudinal study evaluated 43 depressed patients undergoing ECT and 24 controls. MRI and clinical assessments were performed at baseline (V1), after 5 sessions (V2), and post-treatment (V3). Evaluations included a 3 T MR-scan with 3DT1-weighted and multi-shell diffusion (b = 200/1500/2500 s/mm², 30/45/60directions) sequences. Q-ball, Diffusion Tensor, and NODDI models provided: axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), generalized FA (GFA), neurite density index (NDI), isotropic fraction (Fiso), and orientation dispersion index (ODI). FreeSurfer extracted whole hippocampal and subfield volumes from T1-weighted images. Longitudinal changes were assessed with linear mixed-effect models. 107 MRIs from patients and 24 MRIs from controls were analyzed. ECT induced significant bilateral hippocampal volume increases (p < 0.001). Group comparisons showed consistently higher FA, lower GFA and ODI in patients compared to controls at all time-points. Following ECT, significant diffusion changes included decreased hippocampal GFA, FA, AD, MD and Fiso, along with increased ODI and NDI. NDI and Fiso changes were localized to the dentate gyrus but not the hippocampal tail. ECT responders showed a significant right hippocampal volume increase at V2 compared to non-responders. After ECT, hippocampal volume increases are accompanied by bilateral changes in NODDI parameters, particularly in the dentate gyrus, consistent with hippocampal neuroplasticity.

To assess the efficacy of horticultural therapy (HT) on anterior cingulate cortex (ACC) activity and the changes in rumination and catastrophizing scores in individuals with chronic low back pain (LBP). We conducted a randomized, controlled, cross-over, 3-week pilot study (ClinicalTrials.gov Identifier: NCT04656158). The departments of physical medicine and rehabilitation (hospital grounds and occupational therapy room) and imaging research were involved. The participants were adults with non-specific chronic LBP. All participants underwent two 90-min HT sessions and two 90-min handiwork sessions per week. The activity sequence order was randomized, and the activities were separated by a wash-out period of 1 week. Each participant underwent 3 brain MRIs: before, after the first, and after the second activity. The primary outcome was the change in ACC perfusion in ml/100g/min using arterial spin labeling MRI. The secondary outcomes were the changes in self-reported rumination and catastrophizing scores after each activity compared to baseline. Sixteen participants were included: 14 women (87.5%), LBP intensity (numeric rating scale) mean (SD) 45.1 (27.2)/100, specific activity limitation (Roland Morris disability questionnaire) 9.3 (4.1)/24. Change in ACC perfusion from baseline was -0.1 (10.7), 95% CI [-5.6, 5.8] ml (blood)/100g (tissue)/min after handiwork and -0.1 (8.7), [-4.7, 4.6] after HT and did not differ between the 2 activities (p = 0.91). Change in rumination [-0.5 (4.4) after handiwork and -0.3 (2.8) after HT] and catastrophizing scores [-2 (2.8) after handiwork and -1.4 (2.3) after HT] did not differ between activities (p = 0.99 and 0.22, respectively). Limited exposure to the interventions and the sample profile (moderate levels of pain) may explain our results. Our results highlight the need for future studies using the most appropriate outcomes to determine the exact effects of nature experiences in people with chronic musculoskeletal disease.

Background: Catatonia is a psychomotor syndrome frequently observed in disorders with neurodevelopmental impairments, including psychiatric disorders such as schizophrenia. The orbitofrontal cortex (OFC) has been repeatedly associated with catatonia. It presents with an important interindividual morphological variability, with three distinct H-shaped sulcal patterns, types I, II, and III, based on the continuity of the medial and lateral orbital sulci. Types II and III have been identified as neurodevelopmental risk factors for schizophrenia. The sulcal pattern of the OFC has never been investigated in catatonia despite the role of the OFC in the pathophysiology and the neurodevelopmental component of catatonia. Methods: In this context, we performed a retrospective analysis of the OFC sulcal pattern in carefully selected homogeneous and matched subgroups of schizophrenia patients with catatonia (N = 58) or without catatonia (N = 65), and healthy controls (N = 82). Results: Logistic regression analyses revealed a group effect on OFC sulcal pattern in the left (χ² = 18.1; p < .001) and right (χ² = 28.3; p < .001) hemispheres. Catatonia patients were found to have more type III and less type I in both hemispheres compared to healthy controls and more type III on the left hemisphere compared to schizophrenia patients without catatonia. Conclusion: Because the sulcal patterns are indirect markers of early brain development, our findings support a neurodevelopmental origin of catatonia and may shed light on the pathophysiology of this syndrome.