Presence of a central vein within white matter lesions on susceptibility weighted imaging: a specific finding for multiple sclerosis?

INTRODUCTION: Susceptibility weighted imaging depicts the perivenous extent of multiple sclerosis white matter lesions (MS-WML) in vivo by directly visualizing their centrally running vein. The aim of this study was to investigate the specificity of this finding for MS. METHODS: Fifteen patients with MS and 15 patients with microangiopathic white matter lesions (mWML) underwent 3T MRI, including a fluid-attenuated inversion recovery sequence (FLAIR) and a susceptibility weighted angiography (SWAN). All WMLs were identified on FLAIR and assigned to one of the following localizations: supratentorial peripheral, supratentorial periventricular, or infratentorial. Subsequently, the presence of a central vein within these lesions was assessed on SWAN. RESULTS: A total of 711 MS-WMLs and 1,119 m-WMLs were identified on FLAIR, all of which could also be visualized on SWAN. A central vein was detectable in 80% of the MS-WMLs and in 78% of the m-WMLs (in 73% and 76% of the peripheral, in 92% and 94% of the periventricular, and in 71% and 75% of the infratentorial MS-WMLs and m-WMLs, respectively). With regard to the supratentorial peripheral lesions, significantly more m-WMLs showed a central vein compared to the MS-WMLs. For the other localizations, there was no significant difference between the groups with regard to the percentage of lesions with central vein. CONCLUSIONS: Our results indicate that the detection of a central vein within a WML should not be considered a specific finding for MS; it is also found in WMLs of other etiologies.

Reduced B12 uptake and increased gastrointestinal formate are associated with archaeome-mediated breath methane emission in humans.

BACKGROUND: Methane is an end product of microbial fermentation in the human gastrointestinal tract. This gas is solely produced by an archaeal subpopulation of the human microbiome. Increased methane production has been associated with abdominal pain, bloating, constipation, IBD, CRC or other conditions. Twenty percent of the (healthy) Western populations innately exhale substantially higher amounts (>5 ppm) of this gas. The underlying principle for differential methane emission and its effect on human health is not sufficiently understood. RESULTS: We assessed the breath methane content, the gastrointestinal microbiome, its function and metabolome, and dietary intake of one-hundred healthy young adults (female: n = 52, male: n = 48; mean age =24.1). On the basis of the amount of methane emitted, participants were grouped into high methane emitters (CH4 breath content 5-75 ppm) and low emitters (CH4 < 5 ppm). The microbiomes of high methane emitters were characterized by a 1000-fold increase in Methanobrevibacter smithii. This archaeon co-occurred with a bacterial community specialized on dietary fibre degradation, which included members of Ruminococcaceae and Christensenellaceae. As confirmed by metagenomics and metabolomics, the biology of high methane producers was further characterized by increased formate and acetate levels in the gut. These metabolites were strongly correlated with dietary habits, such as vitamin, fat and fibre intake, and microbiome function, altogether driving archaeal methanogenesis. CONCLUSIONS: This study enlightens the complex, multi-level interplay of host diet, genetics and microbiome composition/function leading to two fundamentally different gastrointestinal phenotypes and identifies novel points of therapeutic action in methane-associated disorders. Video Abstract.

Reduced olfactory sensitivity in subjects with depressive symptoms.

BACKGROUND: Clinical studies suggest that olfactory sensitivity is reduced in major depression. Nevertheless, only little is known about the relationship between depressive symptoms and olfactory functions in healthy subjects. METHODS: The present study investigated the association between depressive symptoms and olfactory performance in 48 healthy subjects (14 male). First depressive symptoms were assessed using the Beck Depression Inventory, following by olfactory testing. Olfactory threshold and discrimination performance was assessed as well as emotional arousal and pleasantness during the testing procedure. RESULTS: We observed a significant negative correlation between olfactory sensitivity and depressive symptoms while olfactory discrimination was not related to depressive symptoms. LIMITATIONS: The degree of depressive symptoms was assessed by questionnaire. A clinical interview might assess depressive symptoms more accurate. CONCLUSION: We conclude that depressive symptoms are related to a reduced olfactory sensitivity. The observed relation between reduced olfactory sensitivity and depressive symptoms could be mediated by functional deviations within brain structures subserving primary olfactory processing such as amygdala and piriform cortex which is in line with results showing abnormal activity pattern in the amygdala and other brain regions in depression.

Brain activation predicts treatment improvement in patients with major depressive disorder.

Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.

Functional connectivity of emotional processing in depression.

OBJECTIVES: The aim of the study is to map a neural network of emotion processing and to identify differences in major depression compared to healthy controls. It is hypothesized that intentional perception of emotional faces activates connections between amygdala (Demir et al.), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and prefrontal cortex (PFC) and that frontal-amygdala connections are altered in major depressive disorder (MDD). METHODS: Fifteen medication-free patients with MDD and fifteen healthy controls were enrolled. All subjects were assessed using the same face-matching functional Magnetic Resonance Imaging (fMRI) task, known to involve those areas. Brain activations were obtained using Statistical Parametric Mapping version 5 (SPM5) for data analysis and MARSBAR for extracting of fMRI time series. Then data was analyzed using structural equation modeling (SEM). RESULTS: A valid model was established for the left and the right hemispheres showing a circuit involving ACC, OFC, PFC and AMY. The left hemisphere shows significant lower connectivity strengths in patients than controls, for the pathway that goes from AMY to the OF11, and a trend of higher connectivity in patients for the path that goes from the PF9 to the OF11. In the right hemisphere, patients show lower connectivity coefficients in the paths from the AMY to OF11, from the AMY to ACC, and from the ACC to PF9. By the contrary, controls show lower connectivity strengths for the path that goes from ACC to AMY. CONCLUSIONS: Functional disconnection between limbic and frontal brain regions could be demonstrated using structural equation modeling. The interpretation of these findings could be that there is an emotional processing bias with disconnection bilaterally between amygdala to orbitofrontal cortices and in addition a right disconnection between amygdala and ACC as well as between ACC and prefrontal cortex possibly in line with a more prominent role for the right hemisphere in emotion processing.

Different effects of mirtazapine and venlafaxine on brain activation: an open randomized controlled fMRI study.

OBJECTIVE: Antidepressants with different mechanisms of action might have different effects on brain functions. The aim of the study was therefore to investigate effects of 2 antidepressants on brain activation and to identify predictors for therapy response. METHOD: Twenty-four untreated patients with major depressive disorder (according to Structured Clinical Interview for DSM-IV) were enrolled in a prospective, randomized, 4-week trial with mirtazapine and venlafaxine. Functional magnetic resonance imaging (fMRI) was performed at baseline and after 4 weeks in the patients and in 15 healthy controls. The primary outcome measure was fMRI blood-oxygen-level dependence (BOLD) activation. The patients were recruited in 2007 and 2008. RESULTS: Comparison between patients and controls revealed that emotional face matching elicited enhanced activation in the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, and basal ganglia in patients. During treatment, a significant decrease of BOLD responses was seen in the hippocampus, basal ganglia, thalamus, and cerebellum of venlafaxine-treated patients, and a significant increase in BOLD responses was seen in the middle cingulate gyrus and supplementary motor area of mirtazapine-treated patients (P < .05, family wise error [FWE] cluster-level corrected). Larger BOLD responses in the left fusiform gyrus at baseline predicted a better response to venlafaxine, and smaller BOLD responses in the right rolandic operculum at baseline predicted a better response to mirtazapine (P < .05, FWE cluster-level corrected). CONCLUSIONS: These fMRI results indicate that antidepressants with different mechanisms of action have different effects on brain function. It therefore seems that fMRI can be used for therapy evaluation and response prediction and can facilitate the development of new pharmaceuticals.

Functional connectivity bias of the orbitofrontal cortex in drug-free patients with major depression.

BACKGROUND: The orbitofrontal cortex (OFC) plays a crucial role in emotion-processing circuits and should therefore also be included in models of the pathophysiology of major depression. The aim of this study was to compare the functional connectivity of the OFC during emotion processing in patients with major depression and healthy control subjects. METHODS: Twenty-five untreated patients with major depression and 15 healthy control subjects were investigated using a functional magnetic resonance imaging face-matching task. RESULTS: Dorsal anterior cingulate cortex, precuneus, and cerebellum activity showed less connectivity with the OFC in patients than in control subjects. In contrast, functional connectivity between the OFC and the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal operculum, and left motor areas was increased in patients compared with healthy control subjects. CONCLUSIONS: The OFC plays a key role in the pathophysiology of major depression. The observed imbalance of OFC connectivity seems to represent a neural mechanism of the processing bias. From a neurobiological point of view, the uncoupling of precuneus and gyrus cinguli activity from the OFC might be associated with problems in the regulation of self-schemas, whereas the increased connectivity of the DLPFC to the OFC might represent a higher neural response to negative stimuli.