Asymmetry of planum temporale constrains interhemispheric language plasticity in children with focal epilepsy.

Reorganization of eloquent cortex enables rescue of language functions in patients who sustain brain injury. Individuals with left-sided, early-onset focal epilepsy often show atypical (i.e. bilateral or right-sided) language dominance. Surprisingly, many patients fail to show such interhemispheric shift of language despite having major epileptogenic lesions in close proximity to eloquent cortex. Although a number of epilepsy-related factors may promote interhemispheric plasticity, it has remained unexplored if neuroanatomical asymmetries linked to human language dominance modify the likelihood of atypical lateralization. Here we examined the asymmetry of the planum temporale, one of the most striking asymmetries in the human brain, in relation to language lateralization in children with left-sided focal epilepsy. Language functional magnetic resonance imaging was performed in 51 children with focal epilepsy and left-sided lesions and 36 healthy control subjects. We examined the association of language laterality with a range of potential clinical predictors and the asymmetry of the length of the planum temporale. Using voxel-based methods, we sought to determine the effect of lesion location (in the affected left hemisphere) and grey matter density (in the unaffected right hemisphere) on language laterality. Atypical language lateralization was observed in 19 patients (38%) and in four controls (11%). Language laterality was increasingly right-sided in patients who showed atypical handedness, a left perisylvian ictal electroencephalographic focus, and a lesion in left anterior superior temporal or inferior frontal regions. Most striking was the relationship between rightward asymmetry of the planum temporale and atypical language (R = 0.70, P < 0.0001); patients with a longer planum temporale in the right (unaffected) hemisphere were more likely to have atypical language dominance. Voxel-based regression analysis confirmed that increased grey matter density in the right temporo-parietal junction was correlated with right hemisphere lateralization of language. The length of the planum temporale in the right hemisphere was the main predictor of language lateralization in the epilepsy group, accounting for 48% of variance, with handedness accounting for only a further 5%. There was no correlation between language lateralization and planum temporale asymmetry in the control group. We conclude that asymmetry of the planum temporale may be unrelated to language lateralization in healthy individuals, but the size of the right, contra-lesional planum temporale region may reflect a 'reserve capacity' for interhemispheric language reorganization in the presence of a seizure focus and lesions within left perisylvian regions

‘What’s the plan?’ ‘What plan?’ Changing aspirations among Gypsy youngsters, and implications for future cultural identities and group membership

PublishedMartin Levinson University of Exeter Graduate School of Education Heavitree Road Exeter EX1 2LU United KingdomArticleThis is an Accepted Manuscript of an article published by Taylor & Francis in British Journal of Sociology of Education on 28 March 2014, available online: http://wwww.tandfonline.com/10.1080/01425692.2014.897217Copyright © 2014 Taylor & FrancisConsidering data from a research project with two Gypsy communities (2010–2012) in South West England, this article explores issues of education and identity. The two communities have contrasting experiences within the education system. Informed by inter-disciplinary perspectives on identity and assimilation theories, the article explores these experiences within the wider context of the researcher’s work with Romani communities over the past two decades, exploring the impact of schooling on cultural identity and group membership. Questions are raised about theories concerning hybrid and multiple identities. Finally, the author emphasizes the need to acknowledge the heterogeneity of minority groups in formulating policy

Patients’ Preference and Experiences of Forced Medication and Seclusion

This study examined patients’ preferences for coercive methods and the extent to which patients’ choices were determined by previous experience, demographic, clinical and intervention-setting variables. Before discharge from closed psychiatric units, 161 adult patients completed a questionnaire. The association between patients’ preferences and the underlying variables was analyzed using logistic regression. We found that patients’ preferences were mainly defined by earlier experiences: patients without coercive experiences or who had had experienced seclusion and forced medication, favoured forced medication. Those who had been secluded preferred seclusion in future emergencies, but only if they approved its duration. This suggests that seclusion, if it does not last too long, does not have to be abandoned from psychiatric practices. In an emergency, however, most patients prefer to be medicated. Our findings show that patients’ preferences cannot guide the establishment of international uniform methods for managing violent behaviour. Therefore patients’ individual choices should be considered

V-ATPase-Mediated Granular Acidification Is Regulated by the V-ATPase Accessory Subunit Ac45 in POMC-Producing Cells

The regulation of the V-ATPase, the proton pump mediating intraorganellar acidification, is still elusive. We find that excess of the neuroendocrine V-ATPase accessory subunit Ac45 reduces the intragranular pH and consequently disturbs prohormone convertase activation and prohormone processing. Thus, Ac45 represents the first V-ATPase regulator

Microautophagy of the Nucleus Coincides with a Vacuolar Diffusion Barrier at Nuclear–Vacuolar Junctions

Nuclear-vacuolar (NV) junctions are organelle contact sites in yeast. They exclude nuclear pores from the organelle interface. On the vacuolar side, a lipid-dependent process excludes specific membrane proteins, such as V-ATPase, from the contact site. This suggests that NV junctions establish selective diffusion barriers

Leftward Lateralization of Auditory Cortex Underlies Holistic Sound Perception in Williams Syndrome

BACKGROUND: Individuals with the rare genetic disorder Williams-Beuren syndrome (WS) are known for their characteristic auditory phenotype including strong affinity to music and sounds. In this work we attempted to pinpoint a neural substrate for the characteristic musicality in WS individuals by studying the structure-function relationship of their auditory cortex. Since WS subjects had only minor musical training due to psychomotor constraints we hypothesized that any changes compared to the control group would reflect the contribution of genetic factors to auditory processing and musicality. METHODOLOGY/PRINCIPAL FINDINGS: Using psychoacoustics, magnetoencephalography and magnetic resonance imaging, we show that WS individuals exhibit extreme and almost exclusive holistic sound perception, which stands in marked contrast to the even distribution of this trait in the general population. Functionally, this was reflected by increased amplitudes of left auditory evoked fields. On the structural level, volume of the left auditory cortex was 2.2-fold increased in WS subjects as compared to control subjects. Equivalent volumes of the auditory cortex have been previously reported for professional musicians. CONCLUSIONS/SIGNIFICANCE: There has been an ongoing debate in the neuroscience community as to whether increased gray matter of the auditory cortex in musicians is attributable to the amount of training or innate disposition. In this study musical education of WS subjects was negligible and control subjects were carefully matched for this parameter. Therefore our results not only unravel the neural substrate for this particular auditory phenotype, but in addition propose WS as a unique genetic model for training-independent auditory system properties

Electrophysiological evidence for an early processing of human voices

<p>Abstract</p> <p>Background</p> <p>Previous electrophysiological studies have identified a "voice specific response" (VSR) peaking around 320 ms after stimulus onset, a latency markedly longer than the 70 ms needed to discriminate living from non-living sound sources and the 150 ms to 200 ms needed for the processing of voice paralinguistic qualities. In the present study, we investigated whether an early electrophysiological difference between voice and non-voice stimuli could be observed.</p> <p>Results</p> <p>ERPs were recorded from 32 healthy volunteers who listened to 200 ms long stimuli from three sound categories - voices, bird songs and environmental sounds - whilst performing a pure-tone detection task. ERP analyses revealed voice/non-voice amplitude differences emerging as early as 164 ms post stimulus onset and peaking around 200 ms on fronto-temporal (positivity) and occipital (negativity) electrodes.</p> <p>Conclusion</p> <p>Our electrophysiological results suggest a rapid brain discrimination of sounds of voice, termed the "fronto-temporal positivity to voices" (FTPV), at latencies comparable to the well-known face-preferential N170.</p

γCOP Is Required for Apical Protein Secretion and Epithelial Morphogenesis in Drosophila melanogaster

Background: There is increasing evidence that tissue-specific modifications of basic cellular functions play an important role in development and disease. To identify the functions of COPI coatomer-mediated membrane trafficking in Drosophila development, we were aiming to create loss-of-function mutations in the γCOP gene, which encodes a subunit of the COPI coatomer complex. Principal Findings: We found that γCOP is essential for the viability of the Drosophila embryo. In the absence of zygotic γCOP activity, embryos die late in embryogenesis and display pronounced defects in morphogenesis of the embryonic epidermis and of tracheal tubes. The coordinated cell rearrangements and cell shape changes during tracheal tube morphogenesis critically depend on apical secretion of certain proteins. Investigation of tracheal morphogenesis in γCOP loss-of-function mutants revealed that several key proteins required for tracheal morphogenesis are not properly secreted into the apical lumen. As a consequence, γCOP mutants show defects in cell rearrangements during branch elongation, in tube dilation, as well as in tube fusion. We present genetic evidence that a specific subset of the tracheal defects in γCOP mutants is due to the reduced secretion of the Zona Pellucida protein Piopio. Thus, we identified a critical target protein of COPI-dependent secretion in epithelial tube morphogenesis. Conclusions/Significance: These studies highlight the role of COPI coatomer-mediated vesicle trafficking in both general and tissue-specific secretion in a multicellular organism. Although COPI coatomer is generally required for protein secretion, we show that the phenotypic effect of γCOP mutations is surprisingly specific. Importantly, we attribute a distinct aspect of the γCOP phenotype to the effect on a specific key target protein

A Blueprint for Real-Time Functional Mapping via Human Intracranial Recordings

International audienceBACKGROUND: The surgical treatment of patients with intractable epilepsy is preceded by a pre-surgical evaluation period during which intracranial EEG recordings are performed to identify the epileptogenic network and provide a functional map of eloquent cerebral areas that need to be spared to minimize the risk of post-operative deficits. A growing body of research based on such invasive recordings indicates that cortical oscillations at various frequencies, especially in the gamma range (40 to 150 Hz), can provide efficient markers of task-related neural network activity. PRINCIPAL FINDINGS: Here we introduce a novel real-time investigation framework for mapping human brain functions based on online visualization of the spectral power of the ongoing intracranial activity. The results obtained with the first two implanted epilepsy patients who used the proposed online system illustrate its feasibility and utility both for clinical applications, as a complementary tool to electrical stimulation for presurgical mapping purposes, and for basic research, as an exploratory tool used to detect correlations between behavior and oscillatory power modulations. Furthermore, our findings suggest a putative role for high gamma oscillations in higher-order auditory processing involved in speech and music perception. CONCLUSION/SIGNIFICANCE: The proposed real-time setup is a promising tool for presurgical mapping, the investigation of functional brain dynamics, and possibly for neurofeedback training and brain computer interfaces

SMF-1, SMF-2 and SMF-3 DMT1 Orthologues Regulate and Are Regulated Differentially by Manganese Levels in C. elegans

Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode C. elegans, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in C. elegans: smf-1, smf-2 and smf-3. All three can functionally substitute for loss of their yeast orthologues in S. cerevisiae. In the worm, deletion of smf-1 or smf-3 led to an increased Mn tolerance, while loss of smf-2 led to increased Mn sensitivity. smf mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in smf mutants revealed that SMF-3 is required for normal Mn uptake, while smf-1 was dispensable. Higher smf-2 mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In smf-1 and smf-3 but not in smf-2 mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in C. elegans