Modifications structuro-fonctionnelles cérébrales chez des sujets dépressifs sévères avant et après traitement par électroconvulsivothérapie : étude exploratoire ECTIM

Introduction : L'électroconvulsivothérapie (ECT) est un traitement non pharmacologique du trouble dépressif résistant. Bien que son efficacité ait été démontrée dans cette indication, les mécanismes cérébraux qui sous-tendent ce processus restent très imprécis. Il n'existe actuellement pas de travail étudiant l'effet d'une ECT efficace au niveau des modifications structurofonctionnelles cérébrales. Il semble primordial de poursuivre l'étude des corrélats neuroanatomiques précoces et plus tardifs sous tendant les processus neurofonctionnels responsables de l'amélioration de la clinique. Méthodes : Il s'agit d'une étude mono centrique menée sur le CHU de Toulouse. Chez des patients présentant un trouble dépressif résistant, des évaluations cliniques et en IRM multimodale sont réalisées à 4 temps. La 1ère évaluation a lieu avant le début de la cure, la 2ème après une 1ère ECT, la 3ème après une 1ère ECT efficace et la 4ème après rémission.Résultats: Concernant le volume de l'hippocampe et de l'amygdale à la première visite n'était pas diffèrent du volume à la troisième visite (t(135) = .329, p = .94). Au contraire, il y avait une différence significatif entre le volume de deux structures entre la première et la quatrième visite (t(135) = -2.47, p = .039) et entre la troisième et la quatrième visite (t(135) = -3.51, p = .002). Concernant la diffusivité moyenne en tant que l'effet des visites tend vers la significativité pour la DM (F(2,136) = 2.67, p = .072). En IRM resting state, il existe une hypoconnectivité précoce entre (i) l'hippocampe Droit et le cortex Cingulaire antérieur dorsal (t = -6.20 ; pFDR : 0.0123) ; (ii) l'hippocampe Droit et le noyaux caudé gauche ( t = -7.69 ; pFDR : 0.0035) et (iii) le vermis cervelet et le precuneus (t = -5.93 p FDR : 0.0363). Il existe une hyperconnectivité entre V4 et V1 entre (i) le cortex orbito frontal médian droit et le gyrus occipital médian (t = 6.58 ; p FDR : 0.0146) et (ii) le gyrus frontal inférieur droit et le cortex fronto median gauche (t = 6.83 ; pFDR : 0.0104). Il existe une diminution significative des symptomes de depression entre la V4 et la V1 à l'échelle d'Hamilton (V4: 3,08 ET : 1,62 ; V1 : 23,17 ET : 3,21 ; p <0.001).Conclusion : Il semble exister des modifications structuro-fonctionnelle à l'issu de la cure d'ECT sans modifications structurelles et micro structurelles précoces.Background: Electroconvulsive Therapy (ECT) is a non-pharmacological treatment of resistant depressive disorder. Although its efficacy has been demonstrated in this indication, the brain mechanisms underlying this process remain very imprecise. There is currently no work studying the effect of one effective ECT on cerebral structural changes. It seems essential to continue the study of the early and late neuroanatomical correlates underlying neurofunctional processes responsible for improving the clinic. Methods: This is a mono-centric study conducted on the Toulouse University Hospital. In patients with resistant depressive disorder, clinical and multimodal MRI assessments are performed at 4-step intervals. The first evaluation takes place before the beginning of the treatment, the 2nd after a 1st ECT, the 3rd after a 1st effective ECT and the 4th after remission. Results: Regarding the volume of the hippocampus and amygdala at the first visit was not different from the volume at the third visit (t (135) = .329, p = .94). On the contrary, there was a significant difference between the volume of two structures between the first and the fourth visit (t (135) = -2.47, p = .039) and between the third and fourth visits (t (135) = -3.51, p = .002). For mean diffusivity, the effect of visits showed a trend toward significance for MD (F (2.136) = 2.67, p = .072). In the MRI resting state, there is early hypoconnectivity between (i) the right hippocampus and the dorsal anterior cingulate cortex (t = -6.20, pFDR: 0.0123); (ii) right hippocampus and left caudate nucleus (t = -7.69, pFDR: 0.0035) and (iii) vermis cerebellum and precuneus (t = -5.93 p FDR: 0.0363). There is hyperconnectivity between V4 and V1 between (i) the right medial orbit frontal cortex and the medial occipital gyrus (t = 6.58; p FDR: 0.0146) and (ii) the right inferior frontal gyrus and left fronto medial cortex (t = 6.83, pFDR: 0.0104). There is a significant decrease in the symptoms of depression between V4 and V1 at the Hamilton scale (V4: 3.08 AND: 1.62, V1: 23.17 AND: 3.21, p <0.001). Conclusion: There appears to be structural-functional changes at the end of the ECT course. However, we do not find early structural and micro structural changes

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0–60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0–27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0–30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms

How is tailored implementation undertaken using a self-guided toolkit? Qualitative study of the ItFits-toolkit in the ImpleMentAll project

BackgroundThe process of tailored implementation is ill-defined and under-explored. The ItFits-toolkit was developed and subsequently tested as a self-guided online platform to facilitate implementation of tailored strategies for internet-based cognitive behavioural therapy (iCBT) services. In ImpleMentAll, ItFits-toolkit had a small but positive effect on the primary outcome of iCBT normalisation. This paper investigates, from a qualitative perspective, how implementation teams developed and undertook tailored implementation using the toolkit within the trial.MethodsImplementation teams in thirteen sites from nine countries (Europe and Australia) used the ItFits-toolkit for six months minimum, consistent with the trial protocol. A qualitative process evaluation was conducted. Descriptive data regarding goals, barriers, strategies, and implementation plans collected within the toolkit informed qualitative data collection in real time. Qualitative data included remote longitudinal interviews (n = 55) with implementation team members (n = 30) and observations of support calls (n = 19) with study sites. Qualitative data were analysed thematically, using a team-based approach.ResultsImplementation teams developed and executed tailored implementation projects across all steps in the toolkit process. Working in a structured way but with room for flexibility, decisions were shaped by team members' ideas and goals, iterative stakeholder engagement, internal and external influences, and the context of the ImpleMentAll project. Although teams reported some positive impacts of their projects, 'time', both for undertaking the work, and for seeing project impacts, was described as a key factor in decisions about implementation strategies and assessments of success.ConclusionThis study responds directly to McHugh et al.'s (2022) call for empirical description of what implementation tailoring looks like in action, in service settings. Self-guided facilitation of tailored implementation enables implementers in service settings to undertake tailoring within their organisations. Implementation tailoring takes considerable time and involves detailed work but can be supported through the provision of implementation science informed guidance and materials, iterative and ongoing stakeholder engagement, and working reflectively in response to external influencing factors. Directions for advancement of tailored implementation are suggested

Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = -2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression

Electroconvulsive therapy and cognitive performance from the Global ECT MRI Research Collaboration

The Global ECT MRI Research Collaboration (GEMRIC) has collected clinical and neuroimaging data of patients treated with electroconvulsive therapy (ECT) from around the world. Results to date have focused on neuroimaging correlates of antidepressant response. GEMRIC sites have also collected longitudinal cognitive data. Here, we summarize the existing GEMRIC cognitive data and provide recommendations for prospective data collection for future ECT-imaging investigations. We describe the criteria for selection of cognitive measures for mega-analyses: Trail Making Test Parts A (TMT-A) and B (TMT-B), verbal fluency category (VFC), verbal fluency letter (VFL), and percent retention from verbal learning and memory tests. We performed longitudinal data analysis focused on the pre-/post-ECT assessments with healthy comparison (HC) subjects at similar timepoints and assessed associations between demographic and ECT parameters with cognitive changes. The study found an interaction between electrode placement and treatment number for VFC (F(1,107) = 4.14, p = 0.04). Higher treatment was associated with decreased VFC performance with right unilateral electrode placement. Percent retention showed a main effect for group, with post-hoc analysis indicating decreased cognitive performance among the HC group. However, there were no significant effects of group or group interactions observed for TMT-A, TMT-B, or VFL. We assessed the current GEMRIC cognitive data and acknowledge the limitations associated with this data set including the limited number of neuropsychological domains assessed. Aside from the VFC and treatment number relationship, we did not observe ECT-mediated neurocognitive effects in this investigation. We provide prospective cognitive recommendations for future ECT-imaging investigations focused on strong psychometrics and minimal burden to subjects

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&amp;cond=depression&amp;cntry=FR&amp;rank=

Structural-functional brain changes in depressed patients before and after treatment with electroconvulsive therapy : a pilot study ECTIM

Introduction : L'électroconvulsivothérapie (ECT) est un traitement non pharmacologique du trouble dépressif résistant. Bien que son efficacité ait été démontrée dans cette indication, les mécanismes cérébraux qui sous-tendent ce processus restent très imprécis. Il n'existe actuellement pas de travail étudiant l'effet d'une ECT efficace au niveau des modifications structurofonctionnelles cérébrales. Il semble primordial de poursuivre l'étude des corrélats neuroanatomiques précoces et plus tardifs sous tendant les processus neurofonctionnels responsables de l'amélioration de la clinique. Méthodes : Il s'agit d'une étude mono centrique menée sur le CHU de Toulouse. Chez des patients présentant un trouble dépressif résistant, des évaluations cliniques et en IRM multimodale sont réalisées à 4 temps. La 1ère évaluation a lieu avant le début de la cure, la 2ème après une 1ère ECT, la 3ème après une 1ère ECT efficace et la 4ème après rémission.Résultats: Concernant le volume de l'hippocampe et de l'amygdale à la première visite n'était pas diffèrent du volume à la troisième visite (t(135) = .329, p = .94). Au contraire, il y avait une différence significatif entre le volume de deux structures entre la première et la quatrième visite (t(135) = -2.47, p = .039) et entre la troisième et la quatrième visite (t(135) = -3.51, p = .002). Concernant la diffusivité moyenne en tant que l'effet des visites tend vers la significativité pour la DM (F(2,136) = 2.67, p = .072). En IRM resting state, il existe une hypoconnectivité précoce entre (i) l'hippocampe Droit et le cortex Cingulaire antérieur dorsal (t = -6.20 ; pFDR : 0.0123) ; (ii) l'hippocampe Droit et le noyaux caudé gauche ( t = -7.69 ; pFDR : 0.0035) et (iii) le vermis cervelet et le precuneus (t = -5.93 p FDR : 0.0363). Il existe une hyperconnectivité entre V4 et V1 entre (i) le cortex orbito frontal médian droit et le gyrus occipital médian (t = 6.58 ; p FDR : 0.0146) et (ii) le gyrus frontal inférieur droit et le cortex fronto median gauche (t = 6.83 ; pFDR : 0.0104). Il existe une diminution significative des symptomes de depression entre la V4 et la V1 à l'échelle d'Hamilton (V4: 3,08 ET : 1,62 ; V1 : 23,17 ET : 3,21 ; p <0.001).Conclusion : Il semble exister des modifications structuro-fonctionnelle à l'issu de la cure d'ECT sans modifications structurelles et micro structurelles précoces.Background: Electroconvulsive Therapy (ECT) is a non-pharmacological treatment of resistant depressive disorder. Although its efficacy has been demonstrated in this indication, the brain mechanisms underlying this process remain very imprecise. There is currently no work studying the effect of one effective ECT on cerebral structural changes. It seems essential to continue the study of the early and late neuroanatomical correlates underlying neurofunctional processes responsible for improving the clinic. Methods: This is a mono-centric study conducted on the Toulouse University Hospital. In patients with resistant depressive disorder, clinical and multimodal MRI assessments are performed at 4-step intervals. The first evaluation takes place before the beginning of the treatment, the 2nd after a 1st ECT, the 3rd after a 1st effective ECT and the 4th after remission. Results: Regarding the volume of the hippocampus and amygdala at the first visit was not different from the volume at the third visit (t (135) = .329, p = .94). On the contrary, there was a significant difference between the volume of two structures between the first and the fourth visit (t (135) = -2.47, p = .039) and between the third and fourth visits (t (135) = -3.51, p = .002). For mean diffusivity, the effect of visits showed a trend toward significance for MD (F (2.136) = 2.67, p = .072). In the MRI resting state, there is early hypoconnectivity between (i) the right hippocampus and the dorsal anterior cingulate cortex (t = -6.20, pFDR: 0.0123); (ii) right hippocampus and left caudate nucleus (t = -7.69, pFDR: 0.0035) and (iii) vermis cerebellum and precuneus (t = -5.93 p FDR: 0.0363). There is hyperconnectivity between V4 and V1 between (i) the right medial orbit frontal cortex and the medial occipital gyrus (t = 6.58; p FDR: 0.0146) and (ii) the right inferior frontal gyrus and left fronto medial cortex (t = 6.83, pFDR: 0.0104). There is a significant decrease in the symptoms of depression between V4 and V1 at the Hamilton scale (V4: 3.08 AND: 1.62, V1: 23.17 AND: 3.21, p <0.001). Conclusion: There appears to be structural-functional changes at the end of the ECT course. However, we do not find early structural and micro structural changes

Modifications structuro-fonctionnelles cérébrales chez des sujets dépressifs sévères avant et après traitement par électroconvulsivothérapie : étude exploratoire ECTIM

Background: Electroconvulsive Therapy (ECT) is a non-pharmacological treatment of resistant depressive disorder. Although its efficacy has been demonstrated in this indication, the brain mechanisms underlying this process remain very imprecise. There is currently no work studying the effect of one effective ECT on cerebral structural changes. It seems essential to continue the study of the early and late neuroanatomical correlates underlying neurofunctional processes responsible for improving the clinic. Methods: This is a mono-centric study conducted on the Toulouse University Hospital. In patients with resistant depressive disorder, clinical and multimodal MRI assessments are performed at 4-step intervals. The first evaluation takes place before the beginning of the treatment, the 2nd after a 1st ECT, the 3rd after a 1st effective ECT and the 4th after remission. Results: Regarding the volume of the hippocampus and amygdala at the first visit was not different from the volume at the third visit (t (135) = .329, p = .94). On the contrary, there was a significant difference between the volume of two structures between the first and the fourth visit (t (135) = -2.47, p = .039) and between the third and fourth visits (t (135) = -3.51, p = .002). For mean diffusivity, the effect of visits showed a trend toward significance for MD (F (2.136) = 2.67, p = .072). In the MRI resting state, there is early hypoconnectivity between (i) the right hippocampus and the dorsal anterior cingulate cortex (t = -6.20, pFDR: 0.0123); (ii) right hippocampus and left caudate nucleus (t = -7.69, pFDR: 0.0035) and (iii) vermis cerebellum and precuneus (t = -5.93 p FDR: 0.0363). There is hyperconnectivity between V4 and V1 between (i) the right medial orbit frontal cortex and the medial occipital gyrus (t = 6.58; p FDR: 0.0146) and (ii) the right inferior frontal gyrus and left fronto medial cortex (t = 6.83, pFDR: 0.0104). There is a significant decrease in the symptoms of depression between V4 and V1 at the Hamilton scale (V4: 3.08 AND: 1.62, V1: 23.17 AND: 3.21, p <0.001). Conclusion: There appears to be structural-functional changes at the end of the ECT course. However, we do not find early structural and micro structural changes.Introduction : L'électroconvulsivothérapie (ECT) est un traitement non pharmacologique du trouble dépressif résistant. Bien que son efficacité ait été démontrée dans cette indication, les mécanismes cérébraux qui sous-tendent ce processus restent très imprécis. Il n'existe actuellement pas de travail étudiant l'effet d'une ECT efficace au niveau des modifications structurofonctionnelles cérébrales. Il semble primordial de poursuivre l'étude des corrélats neuroanatomiques précoces et plus tardifs sous tendant les processus neurofonctionnels responsables de l'amélioration de la clinique. Méthodes : Il s'agit d'une étude mono centrique menée sur le CHU de Toulouse. Chez des patients présentant un trouble dépressif résistant, des évaluations cliniques et en IRM multimodale sont réalisées à 4 temps. La 1ère évaluation a lieu avant le début de la cure, la 2ème après une 1ère ECT, la 3ème après une 1ère ECT efficace et la 4ème après rémission.Résultats: Concernant le volume de l'hippocampe et de l'amygdale à la première visite n'était pas diffèrent du volume à la troisième visite (t(135) = .329, p = .94). Au contraire, il y avait une différence significatif entre le volume de deux structures entre la première et la quatrième visite (t(135) = -2.47, p = .039) et entre la troisième et la quatrième visite (t(135) = -3.51, p = .002). Concernant la diffusivité moyenne en tant que l'effet des visites tend vers la significativité pour la DM (F(2,136) = 2.67, p = .072). En IRM resting state, il existe une hypoconnectivité précoce entre (i) l'hippocampe Droit et le cortex Cingulaire antérieur dorsal (t = -6.20 ; pFDR : 0.0123) ; (ii) l'hippocampe Droit et le noyaux caudé gauche ( t = -7.69 ; pFDR : 0.0035) et (iii) le vermis cervelet et le precuneus (t = -5.93 p FDR : 0.0363). Il existe une hyperconnectivité entre V4 et V1 entre (i) le cortex orbito frontal médian droit et le gyrus occipital médian (t = 6.58 ; p FDR : 0.0146) et (ii) le gyrus frontal inférieur droit et le cortex fronto median gauche (t = 6.83 ; pFDR : 0.0104). Il existe une diminution significative des symptomes de depression entre la V4 et la V1 à l'échelle d'Hamilton (V4: 3,08 ET : 1,62 ; V1 : 23,17 ET : 3,21 ; p <0.001).Conclusion : Il semble exister des modifications structuro-fonctionnelle à l'issu de la cure d'ECT sans modifications structurelles et micro structurelles précoces

Conséquences psychopathologiques de la chirurgie de l'épilepsie

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Structural and functional changes associated with functional/dissociative seizures: A review of the literature

International audienceIntroduction: The term 'functional/dissociative seizures (FDS)' refers to a paroxysmal, transient clinical manifestation that may include motor, sensory, vegetative, psychological and cognitive signs, similar to the manifestations observed in epileptic seizures. In recent years, there has been an increase of literature in the field of brain imaging research on functional neurological disorders and, more specifically, on FDS. However, most of the studies have been carried out on limited samples. We propose an update of this review work by performing a systematic review of studies performed since 2017 in the field of neuroimaging in patients with FDS.Methods: We conducted a systematic review of the literature using the PRISMA methodology and reproduced most of the methodological elements of the latest systematic literature review.Results: Our work over the last five years has identified 14 articles. It is still difficult to isolate a distinct structure or network specifically involved in the mechanism of FDS. However, certain structures are recurrently involved in imaging studies, notably the amygdala, the orbitofrontal cortex, and the anterior cingulate cortex.Conclusion: The contribution of neuroimaging may allow a more precise explanation of the disorder for patients, avoiding the stigma frequently associated with this diagnosis. as with other 'conversion' phenomena which have traditionally been considered only as 'medically unexplained'. In the longer term and beyond a better understanding of the physiopathology of the disorder, the challenge of this neuroimaging work would be to identify specific imaging biomarkers for a diagnosis of FDS