rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). METHODS: 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. RESULTS: N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. CONCLUSIONS: In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients' brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS

Exploring resting state connectivity in patients with psychotic depression

BACKGROUND: Severe depression is associated with high morbidity and mortality. Neural network dysfunction may contribute to disease mechanisms underlying different clinical subtypes. Here, we apply resting-state functional magnetic resonance imaging based measures of brain connectivity to investigate network dysfunction in severely depressed in-patients with and without psychotic symptoms. METHODS: A cohort study was performed at two sites. Older patients with major depressive disorder with or without psychotic symptoms were included (n = 23 at site one, n = 26 at site two). Resting state 3-Tesla functional MRI scans, with eyes closed, were obtained and Montgomery-Åsberg Depression Rating Scales were completed. We denoised data and calculated resting state networks in the two groups separately. We selected five networks of interest (1. bilateral frontoparietal, 2.left lateralized frontoparietal, 3.right lateralized frontoparietal, 4.default mode network (DMN) and 5.bilateral basal ganglia and insula network) and performed regression analyses with severity of depression, as well as presence or absence of psychotic symptoms. RESULTS: The functional connectivity (FC) patterns did not correlate with severity of depression. Depressed patients with psychotic symptoms (n = 14, 61%) compared with patients without psychotic symptoms (n = 9, 39%) from site one showed significantly decreased FC in the right part of the bilateral frontoparietal network (p = 0.002). This result was not replicated when comparing patients with (n = 9, 35%) and without (n = 17, 65%) psychotic symptoms from site two. CONCLUSION: Psychotic depression may be associated with decreased FC of the frontoparietal network, which is involved in cognitive control processes, such as attention and emotion regulation. These findings suggest that FC in the frontoparietal network may be related to the subtype of depression, i.e. presence of psychotic symptoms, rather than severity of depression. Since the findings could not be replicated in the 2nd sample, replication is needed before drawing definite conclusions

The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s00213-020-05597-7.Rationale: OCD is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. Objective: To investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD and healthy controls. Methods: A randomized double-blind crossover study assessed the effects of single dose escitalopram (20mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 hours after oral administration of the pharmacological challenge / placebo, and compared across and within groups using a mixed model ANOVA. Results: On the outcome measure of interest, i.e. the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59)=3.1; p=0.052), with patients (Least square [LS] mean: 1.43; Standard Error [SE]: 0.06; 95% confidence interval [CI], 1.31-1.55) and their relatives (LS mean: 1.46; SE: 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean: 1.26; SE: 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group x treatment interaction (F(2, 58)=2.8, p=0.069), with post hoc tests showing (i) patients (p=0.009; LS mean difference: 0.23; SE: 0.08) and relatives (p=0.03; LS mean difference: 0.22; SE: 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p=0.013; LS mean difference: 0.1; SE: 0.04), but not other groups (both p>0.1; controls: LS mean difference: -0.03; SE: 0.04; relatives: LS mean difference: 0.02; SE: 0.05). Conclusion: Our findings are consistent with a view that there is impaired executive planning in OCD, and that this constitutes a behavioral endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.Peer reviewe

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Brain activation of the defensive and appetitive survival systems in obsessive compulsive disorder

Several studies have shown that basic emotions are responsible for a significant enhancement of early visual processes and increased activation in visual processing brain regions. It may be possible that the cognitive uncertainty and repeated behavioral checking evident in Obsessive Compulsive Disorder (OCD) is due to the existence of abnormalities in basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional-laden stimuli. The objective of the present study was to test if patients with OCD show evidence of altered basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional stimuli. Fifteen patients with OCD and 12 healthy controls underwent functional magnetic resonance imaging acquisition while being exposed to emotional pictures, with different levels of arousal, intended to trigger the defensive and appetitive basic survival circuits. Overall, the present results seem to indicate dissociation in the activity of the defense and appetitive survival systems in OCD. Results suggest that the clinical group reacts to basic threat with a strong activation of the defensive system mobilizing widespread brain networks (i.e., frontal, temporal, occipital-parietal, and subcortical nucleus) and blocking the activation of the appetitive system when facing positive emotional triggers from the initial stages of visual processing (i.e., superior occipital gyrus)

Autism and ADHD Symptoms in Patients with OCD: Are They Associated with Specific OC Symptom Dimensions or OC Symptom Severity?

In obsessive-compulsive disorder (OCD), the relationship between autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and obsessive-compulsive (OC) symptom dimensions and severity has scarcely been studied. Therefore, 109 adult outpatients with primary OCD were compared to 87 healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD and autism symptom frequencies, OCD + ADHD patients reporting more autism symptoms (particularly attention switching and social skills problems) than OCD − ADHD patients. Attention switching problems were most significant predictors of OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not associated with elevated autism scale scores, but with inattention. In conclusion, attention switching problems may reflect both symptom overlap and a common etiological factor underlying ASD, ADHD and OCD

Single cell derived mRNA signals across human kidney tumors.

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer