Emotional Speech Perception Unfolding in Time: The Role of the Basal Ganglia

The basal ganglia (BG) have repeatedly been linked to emotional speech processing in studies involving patients with neurodegenerative and structural changes of the BG. However, the majority of previous studies did not consider that (i) emotional speech processing entails multiple processing steps, and the possibility that (ii) the BG may engage in one rather than the other of these processing steps. In the present study we investigate three different stages of emotional speech processing (emotional salience detection, meaning-related processing, and identification) in the same patient group to verify whether lesions to the BG affect these stages in a qualitatively different manner. Specifically, we explore early implicit emotional speech processing (probe verification) in an ERP experiment followed by an explicit behavioral emotional recognition task. In both experiments, participants listened to emotional sentences expressing one of four emotions (anger, fear, disgust, happiness) or neutral sentences. In line with previous evidence patients and healthy controls show differentiation of emotional and neutral sentences in the P200 component (emotional salience detection) and a following negative-going brain wave (meaning-related processing). However, the behavioral recognition (identification stage) of emotional sentences was impaired in BG patients, but not in healthy controls. The current data provide further support that the BG are involved in late, explicit rather than early emotional speech processing stages

Seeing Emotion with Your Ears: Emotional Prosody Implicitly Guides Visual Attention to Faces

Interpersonal communication involves the processing of multimodal emotional cues, particularly facial expressions (visual modality) and emotional speech prosody (auditory modality) which can interact during information processing. Here, we investigated whether the implicit processing of emotional prosody systematically influences gaze behavior to facial expressions of emotion. We analyzed the eye movements of 31 participants as they scanned a visual array of four emotional faces portraying fear, anger, happiness, and neutrality, while listening to an emotionally-inflected pseudo-utterance (Someone migged the pazing) uttered in a congruent or incongruent tone. Participants heard the emotional utterance during the first 1250 milliseconds of a five-second visual array and then performed an immediate recall decision about the face they had just seen. The frequency and duration of first saccades and of total looks in three temporal windows ([0–1250 ms], [1250–2500 ms], [2500–5000 ms]) were analyzed according to the emotional content of faces and voices. Results showed that participants looked longer and more frequently at faces that matched the prosody in all three time windows (emotion congruency effect), although this effect was often emotion-specific (with greatest effects for fear). Effects of prosody on visual attention to faces persisted over time and could be detected long after the auditory information was no longer present. These data imply that emotional prosody is processed automatically during communication and that these cues play a critical role in how humans respond to related visual cues in the environment, such as facial expressions

Functional KV10.1 Channels Localize to the Inner Nuclear Membrane

Ectopically expressed human KV10.1 channels are relevant players in tumor biology. However, their function as ion channels at the plasma membrane does not totally explain their crucial role in tumors. Both in native and heterologous systems, it has been observed that a majority of KV10.1 channels remain at intracellular locations. In this study we investigated the localization and possible roles of perinuclear KV10.1. We show that KV10.1 is expressed at the inner nuclear membrane in both human and rat models; it co-purifies with established inner nuclear membrane markers, shows resistance to detergent extraction and restricted mobility, all of them typical features of proteins at the inner nuclear membrane. KV10.1 channels at the inner nuclear membrane are not all transported directly from the ER but rather have been exposed to the extracellular milieu. Patch clamp experiments on nuclei devoid of external nuclear membrane reveal the existence of channel activity compatible with KV10.1. We hypothesize that KV10.1 channels at the nuclear envelope might participate in the homeostasis of nuclear K+, or indirectly interact with heterochromatin, both factors known to affect gene expression

It's not what you say but the way that you say it: an fMRI study of differential lexical and non-lexical prosodic pitch processing

<p>Abstract</p> <p>Background</p> <p>This study aims to identify the neural substrate involved in prosodic pitch processing. Functional magnetic resonance imaging was used to test the premise that prosody pitch processing is primarily subserved by the right cortical hemisphere.</p> <p>Two experimental paradigms were used, firstly pairs of spoken sentences, where the only variation was a single internal phrase pitch change, and secondly, a matched condition utilizing pitch changes within analogous tone-sequence phrases. This removed the potential confounder of lexical evaluation. fMRI images were obtained using these paradigms.</p> <p>Results</p> <p>Activation was significantly greater within the right frontal and temporal cortices during the tone-sequence stimuli relative to the sentence stimuli.</p> <p>Conclusion</p> <p>This study showed that pitch changes, stripped of lexical information, are mainly processed by the right cerebral hemisphere, whilst the processing of analogous, matched, lexical pitch change is preferentially left sided. These findings, showing hemispherical differentiation of processing based on stimulus complexity, are in accord with a 'task dependent' hypothesis of pitch processing.</p

Subcellular Localization of SUN2 Is Regulated by Lamin A and Rab5

SUN2 is an inner nuclear membrane protein with a conserved Sad1/UNC-84 homology SUN-domain at the C-terminus. Intriguingly, SUN2 has also been reported to interact with Rab5, which localizes in early endosomes. To clarify the dual subcellular localization of SUN2, we investigated its localization in lamin A/C deficient cells rescued with lamin A or lamin C isoform, and in HeLa cells transfected with Rab5 or its mutants. We found that expression of lamin A but not lamin C partly restored the nuclear envelope localization of SUN2. SUN2 was redistributed to endosomes upon overexpression of Rab5, but remained on the nuclear envelope when the SUN domain was deleted. To explore the physiological function of SUN2 in vesicle trafficking and endocytosis, we demonstrated the colocalization of endogenous SUN2 and Rab5. Moreover, overexpression of SUN2 stimulated the uptake of transferrin while suppression of SUN2 expression attenuated the process. These findings support a role of SUN2 in endocytosis

A murine model of ulcerative colitis: induced with sinusitis-derived superantigen and food allergen

BACKGROUND: The etiology of ulcerative colitis (UC) is to be understood. The basic pathological feature of UC is intestinal chronic inflammation. Superantigen, such as Staphylococcus enterotoxin B (SEB), is reported to compromise intestinal barrier function by increasing epithelial permeability and initiate inflammation in the intestinal mucosa. Inasmuch as anatomic position of the sinus, chronic sinusitis-derived SEB may follow the secretion and to be swallowed down to the gastrointestinal tract and induce lesions to the intestinal mucosa. METHODS: Sinus wash fluid (SWF, containing SEB) was collected from a group of patients with both chronic sinusitis (CS) and UC. A group of mice were sensitized to ovalbumin (OVA) in the presence of SWF. The sensitized mice were challenged with the specific antigen OVA. The inflammatory status of the colonic tissue was determined with histology, serology and electron microscopy. Using horseradish peroxidase (HRP) as a tracer, another group of mice was stimulated with SWF for 2 hours. The HRP activity was detected in the colonic tissue with enzymatic approaches and electron microscopy. RESULTS: Epithelial hyperpermeability in colonic epithelium was induced by stimulating with SWF. The HRP activity in the colonic mucosa was almost 11 times more in the SWF treated group (3.2 ± 0.6 μg/g tissue) than the control group (0.3 ± 0.1 μg/g tissue). Mice were sensitized using a mixture of SWF and OVA (serum OVA-specific IgE was detected with a highest titer as 1:64). Challenge with OVA induced extensive inflammation in the colonic mucosa by showing (1) marked degranulation in mast cells (MC, 46.3 ± 4.5%) and eosinophils (Eo, 55.7 ± 4.2%); (2) inflammatory cell infiltration (MC = 145.2 ± 11.4; Eo = 215.8 ± 12.5; mononuclear cell = 258.4 ± 15.3/mm(2 )tissue); (3) increased MPO activity (12.9 ± 3.2 U/g tissue) and inflammatory scores (1.8 ± 0.3); (4) mucosal surface ulcers; (5) edema in the lamina propria; (6) bacterial translocation and abscess formation in the subepithelial region. CONCLUSION: Introducing Sinusitis-derived SEB-containing SWF to the gastrointestinal tract compromised colonic mucosal barrier function increasing epithelial permeability to luminal macromolecular protein in mice. The SWF facilitated colonic mucosal sensitization to luminal antigen. Multiple challenging the sensitized colonic mucosa with specific antigen OVA induced inflammation, induced a condition similar to human ulcerative colitis

Sex-specific lesion pattern of functional outcomes after stroke.

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level

Results of a pilot study on the involvement of bilateral inferior frontal gyri in emotional prosody perception: an rTMS study

<p>Abstract</p> <p>Background</p> <p>The right hemisphere may play an important role in paralinguistic features such as the emotional melody in speech. The extent of this involvement however is unclear. Imaging studies have shown involvement of both left and right inferior frontal gyri in emotional prosody perception. The present pilot study examined whether these brain areas are critically involved in the processing of emotional prosody and of semantics in 9 healthy subjects. Repetitive transcranial magnetic stimulation was used with a coil centred over left and right inferior frontal gyri, as localized by neuronavigation based on the subject's MRI. A sham condition was included. An online-TMS approach was applied; an emotional language task was completed during stimulation. This computerized task consisted of sentences pronounced by actors. In the semantics condition an emotion (fear, anger or neutral) was expressed in the content pronounced with a neutral intonation. In the prosody condition the emotion was expressed in the intonation, while the content was neutral.</p> <p>Results</p> <p>Reaction times on the emotional prosody task condition were significantly longer after rTMS over both the right and the left inferior frontal gyrus as compared to sham stimulation and after controlling for learning effects associated with order of condition. When taking all emotions together, there was no difference in effect on reaction times between the right and left stimulation. For the emotion Fear, reaction times were significantly longer after stimulating the left inferior frontal gyrus as compared to the right inferior frontal gyrus. Reaction times in the semantics task condition were not significantly different between the three TMS conditions.</p> <p>Conclusions</p> <p>The data indicate a critical involvement of both the right and the left inferior frontal gyrus in emotional prosody perception. The findings of this pilot study need replication. Future studies should include more subjects and examine whether the left and right inferior frontal gyrus play a differential role and complement each other, e.g. in the integrated processing of linguistic and prosodic aspects of speech, respectively.</p

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke

Nuclear envelope protein Lem2 is required for mouse development and regulates MAP and AKT kinases

The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating signaling in the nucleus. Numerous human diseases arise from mutations in lamina proteins, and experimental models for these disorders have revealed aberrant regulation of various signaling pathways. Previously, we reported that the inner nuclear membrane protein Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes, although muscle regeneration induced by cardiotoxin was delayed. By contrast, homozygous Lemd2 knockout mice died by E11.5. Although many normal morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were substantially reduced in size. This was accompanied by activation of multiple MAP kinases (ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential role in mouse embryonic development and that it is involved in regulating several signaling pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered to be another candidate gene for human disease