Real-Time Self-Regulation of Emotion Networks in Patients with Depression

Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression

Nivolumab‐induced celiac‐like enteropathy in patient with metastatic renal cell carcinoma: Case report and review of the literature

International audienceNivolumab may induce severe celiac-like enteropathy, that may appear very rapidly, after only two injections of nivolumab, and may be successfully treated with corticosteroids. This observation underlines the importance of histological analysis of duodenal biopsies and the necessity to rule out a real celiac disease in patients with nivolumab-induced diarrhea

Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment

International audienceAutoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis. Four blood lymphocyte populations were significantly altered in AIHn patients at diagnosis compared with healthy subjects. Levels of mucosal-associated invariant T cells (MAIT), Type 1/Type 17 helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB) cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also observed. These alterations were not restored with standard immunosuppressive treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers were enriched in the hepatic lobule. During remission, the hepatic lobule was clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB) was linked to severe fibrosis. Conclusion: Our work proposes a global view of the lymphocyte alterations from diagnosis to remission phase in AIH patients. The absence of blood immune homeostasis restoration and the persistence of a CD4 infiltrate in the liver under standard immunosuppres-sion could form the basis of the high risk of relapse observed in AIH

Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon Standard Immunosuppressive Treatment

International audienceAutoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis. Four blood lymphocyte populations were significantly altered in AIHn patients at diagnosis compared with healthy subjects. Levels of mucosal-associated invariant T cells (MAIT), Type 1/Type 17 helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB) cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also observed. These alterations were not restored with standard immunosuppressive treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers were enriched in the hepatic lobule. During remission, the hepatic lobule was clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB) was linked to severe fibrosis. Conclusion: Our work proposes a global view of the lymphocyte alterations from diagnosis to remission phase in AIH patients. The absence of blood immune homeostasis restoration and the persistence of a CD4 infiltrate in the liver under standard immunosuppres-sion could form the basis of the high risk of relapse observed in AIH

Neurofeedback protocol.

<p>During the neurofeedback runs (3 in each of the 4 sessions), participants alternated between 20 s periods of rest and 20 s periods where they had to upregulate activity in the target area. The level of activation was fed back in real time (updated for each TR of 2 s) through the thermometer display.</p

Neurofeedback produced clinical improvement that was not seen in the control group.

<p>Patients in the neurofeedback (NF) treatment group, but not those in the imagery (IM) control group, improved significantly on the 17-item Hamilton Depression Rating scale, a standard clinical measure of depression severity and treatment effects. Lower values denote clinical improvement (error bars: standard errors).</p

Network activation and deactivation during neurofeedback.

<p>a) Activation of the insular cortex (INS) bilaterally and the right ventral striatum (VS) supported the neurofeedback task, whereas the temporoparietal junctions (TPJ) of both hemispheres were deactivated. The TPJ is recognised as part of the brain’s “default mode network” that is deactivated during effortful tasks. For a full documentation of the activated and deactivated networks see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038115#pone-0038115-t003" target="_blank">Table 3</a>. View from the front and above. The right side of the brain is on the observer’s left (Talairach coordinates of virtual cuts: y = 25, z = −2). b) Successive training sessions produced further increases of activation during upregulation periods in the VS bilaterally (coronal view at y = 7, the right side of the brain is on the observer’s left).</p

The localiser procedure identified networks of positive mood.

<p>Higher activation of right insula (INS), ventral striatum (VS), anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (VMPFC) during presentation of positive compared to neutral images in the localiser runs (for full list of areas see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038115#pone-0038115-t002" target="_blank">Table 2</a>). The localiser runs were effective in identifying brain areas responsive to positive images, which were used as target regions of interests (ROIs) for the subsequent neurofeedback procedure. The figure shows the contrast map thresholded at p&lt;.05 (cluster level corrected) on a sample brain seen from the right and front (Talairach coordinates of virtual cuts: x = 0, y = 0, z = −2).</p