Functional responses and structural connections of cortical areas for processing faces and voices in the superior temporal sulcus.

It was the aim of this study to delineate the areas along the right superior temporal sulcus (STS) for processing of faces, voices, and face-voice integration using established functional magnetic resonance imaging (fMRI) localizers and to assess their structural connectivity profile with diffusion tensor imaging (DTI). We combined this approach with an fMRI adaptation design during which the participants judged emotions in facial expressions and prosody and demonstrated response habituation in the orbitofrontal cortex (OFC) which occurred irrespective of the sensory modality. These functional data were in line with DTI findings showing separable fiber projections of the three different STS modules converging in the OFC which run through the external capsule for the voice area, through the dorsal superior longitudinal fasciculus (SLF) for the face area and through the ventral SLF for the audiovisual integration area. The OFC was structurally connected with the supplementary motor area (SMA) and activation in these two areas was correlated with faster stimulus evaluation during repetition priming. Based on these structural and functional properties, we propose that the OFC is part of the extended system for perception of emotional information in faces and voices and constitutes a neural interface linking sensory areas with brain regions implicated in generation of behavioral responses.

Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane.

It is assumed that the survival factors Bcl-2 and Bcl-x(L) are mainly functional on mitochondria and therefore must contain mitochondrial targeting sequences. Here we show, however, that only Bcl-x(L) is specifically targeted to the mitochondrial outer membrane (MOM) whereas Bcl-2 distributes on several intracellular membranes. Mitochondrial targeting of Bcl-x(L) requires the COOH-terminal transmembrane (TM) domain flanked at both ends by at least two basic amino acids. This sequence is a bona fide targeting signal for the MOM as it confers specific mitochondrial localization to soluble EGFP. The signal is present in numerous proteins known to be directed to the MOM. Bcl-2 lacks the signal and therefore localizes to several intracellular membranes. The COOH-terminal region of Bcl-2 can be converted into a targeting signal for the MOM by increasing the basicity surrounding its TM. These data define a new targeting sequence for the MOM and propose that Bcl-2 acts on several intracellular membranes whereas Bcl-x(L) specifically functions on the MOM.

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial.

BACKGROUND: Current efforts to improve clinical effectiveness and utility of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression (MD) include theta burst stimulation (TBS), a patterned form of rTMS. Here, we investigated the efficacy of bilateral TBS to the dorsolateral prefrontal cortex (dlPFC) in patients with MD in additon to ongoing medication and psychotherapy. METHODS: In this randomized-controlled trial, thirty-two patients with MD were treated for six weeks (thirty sessions) with either successively intermittent, activity enhancing TBS (iTBS) to the left and continuous, inhibiting TBS (cTBS) to the right dlPFC or with bilateral sham stimulation. Primary outcome measure was the proportion of treatment response defined as a Montgomery-Åsberg Depression Rating Scale (MADRS)≤50% compared to baseline. Secondary outcomes comprised response and remission rates of the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). RESULTS: A larger number of responders were found in the cTBS (n=9) compared to the sham-stimulation (n=4) group (odds ratio: 3.86; Wald χ(2)=3.9, p=0.048). On secondary endpoint analysis, patient-reported outcome as assessed by the BDI, pointed towards a higher rate of remitters in the cTBS (n=6) than in the sham (n=1) group (odds ratio: 9; Wald χ(2)=3.5, p=0.061). LIMITATIONS: With regard to the pilot character of the study and the small sample size, the results have to be considered as preliminary. CONCLUSIONS: These findings provide first evidence that six weeks treatment of MDD with iTBS to the left and cTBS to the right dlPFC for six weeks is safe, feasible and superior to sham stimulation applied add-on to pharmacological and psychotherapeutic treatment.

They are laughing at me: cerebral mediation of cognitive biases in social anxiety.

The fear of embarrassment and humiliation is the central element of social anxiety. This frequent condition is associated with cognitive biases indicating increased sensitivity to signals of social threat, which are assumed to play a causal role in the maintenance of social anxiety. Here, we employed laughter, a potent medium for the expression of acceptance and rejection, as an experimental stimulus in participants selected for varying degrees of social anxiety to identify cerebral mediators of cognitive biases in social anxiety using functional magnetic resonance imaging in combination with mediation analysis. We directly demonstrated that cerebral activation patterns within the dorsal attention network including the left dorsolateral and dorsomedial prefrontal cortex mediate the influence of social anxiety on laughter perception. This mediation proved to be specific for social anxiety after correction for measures of general state and trait anxiety and occurred most prominently under bimodal audiovisual laughter presentation when compared with monomodal auditory or visual laughter cues. Considering the possibility to modulate cognitive biases and cerebral activity by neuropsychological trainings, non-invasive electrophysiological stimulation and psychotherapy, this study represents a starting point for a whole line of translational research projects and identifies promising targets for electrophysiological interventions aiming to alleviate cognitive biases and symptom severity in social anxiety.

Judgment of emotional information expressed by prosody and semantics in patients with unipolar depression.

It was the aim of this study to investigate the impact of major depressive disorder (MDD) on judgment of emotions expressed at the verbal (semantic content) and non-verbal (prosody) level and to assess whether evaluation of verbal content correlate with self-ratings of depression-related symptoms as assessed by Beck Depression Inventory (BDI). We presented positive, neutral, and negative words spoken in happy, neutral, and angry prosody to 23 MDD patients and 22 healthy controls (HC) matched for age, sex, and education. Participants rated the valence of semantic content or prosody on a 9-point scale. MDD patients attributed significantly less intense ratings to positive words and happy prosody than HC. For judgment of words, this difference correlated significantly with BDI scores. No such correlation was found for prosody perception. MDD patients exhibited attenuated processing of positive information which generalized across verbal and non-verbal channels. These findings indicate that MDD is characterized by impairments of positive rather than negative emotional processing, a finding which could influence future psychotherapeutic strategies as well as provide straightforward hypotheses for neuroimaging studies investigating the neurobiological correlates of impaired emotional perception in MDD.

Bcl-x(S) induces an NGF-inhibitable cytochrome c release.

Bcl-x(S), a pro-apoptotic member of the Bcl-2 protein family, is localized in the mitochondrial outer membrane and induces caspase-dependent and nerve growth factor (NGF)-inhibitable apoptosis in PC12 cells. The mechanism of action of Bcl-x(S) and how NGF inhibits this death are not fully understood. It is still unknown whether Bcl-x(S) induces mitochondrial cytochrome c release, and which apoptotic step NGF inhibits. We show that Bcl-x(S) induces cytochrome c release and caspase-3 activation in several cell types, and that in PC12 cells, these events are inhibited by NGF treatment. The survival effect of NGF was inhibited by inhibitors of protein kinase C (PKC), phosphatidylinositol-3-kinase (PI 3-kinase), and the mitogen-activated protein kinase kinase (MEK) inhibitors GF109203X, LY294002, and U0126. These findings show that cytochrome c release and caspase-3 activation participate in Bcl-x(S)-induced apoptosis, and that NGF inhibits Bcl-x(S)-induced apoptosis at the mitochondrial level via the PKC, PI 3-kinase, and MEK signaling pathways.