Visemic processing in audiovisual discrimination of natural speech: a simultaneous fMRI-EEG study

In a noisy environment, visual perception of articulatory movements improves natural speech intelligibility. Parallel to phonemic processing based on auditory signal, visemic processing constitutes a counterpart based on "visemes", the distinctive visual units of speech. Aiming at investigating the neural substrates of visemic processing in a disturbed environment, we carried out a simultaneous fMRI-EEG experiment based on discriminating syllabic minimal pairs involving three phonological contrasts, each bearing on a single phonetic feature characterised by different degrees of visual distinctiveness. The contrasts involved either labialisation of the vowels, or place of articulation or voicing of the consonants. Audiovisual consonant-vowel syllable pairs were presented either with a static facial configuration or with a dynamic display of articulatory movements related to speech production. In the sound-disturbed MRI environment, the significant improvement of syllabic discrimination achieved in the dynamic audiovisual modality, compared to the static audiovisual modality was associated with activation of the occipito-temporal cortex (MT+V5) bilaterally, and of the left premotor cortex. While the former was activated in response to facial movements independently of their relation to speech, the latter was specifically activated by phonological discrimination. During fMRI, significant evoked potential responses to syllabic discrimination were recorded around 150 and 250 ms following the onset of the second stimulus of the pairs, whose amplitude was greater in the dynamic compared to the static audiovisual modality. Our results provide arguments for the involvement of the speech motor cortex in phonological discrimination, and suggest a multimodal representation of speech units.     

Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment

Hajek T, Cullis J, Novak T, Kopecek M, Höschl C, Blagdon R, O’Donovan C, Bauer M, Young L T, MacQueen G, Alda M. Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment.
Bipolar Disord 2012: 14: 261–270. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li). Methods: We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non‐Li group) and 11 healthy controls. All BD patients had at least 10 years of illness and five episodes. We also recruited 13 Li‐naïve, young BD participants (15–30 years of age) and 18 sex‐ and age‐matched healthy controls. We compared hippocampal volumes obtained from 1.5‐T magnetic resonance imaging (MRI) scans using optimized voxel‐based morphometry with small volume correction. Results: The non‐Li group had smaller left hippocampal volumes than controls (corrected p < 0.05), with a trend for lower volumes than the Li group (corrected p < 0.1), which did not differ from controls. Young, Li‐naïve BD patients close to the typical age of onset had comparable hippocampal volumes to controls. Conclusions: Whereas patients with limited lifetime Li exposure had significantly lower hippocampal volumes than controls, patients with comparable illness burden, but with over two years of Li treatment, or young Li‐naïve BD patients, showed hippocampal volumes comparable to controls. These results provide indirect support for neuroprotective effects of Li and negative effects of illness burden on hippocampal volumes in bipolar disorders.     

Microstructure of a three-way anatomical network predicts individual differences in response inhibition: a tractography study

Response inhibition is thought to depend critically on the inferior frontal gyrus, pars opercularis (IFGoper), presupplementary motor area (preSMA) and basal ganglia, including the subthalamic nucleus (STN), but the differential contribution of structural connections within this network to response inhibition remains unclear. Using diffusion tensor imaging and probabilistic fiber tractography, we investigated the relative associations between local white matter microstructure and stop-signal response inhibition in fronto-basal ganglia tracts delineated by probabilistic tractography. In a tract-of-interest approach, we identify significant associations with fractional anisotropy (FA) in fibers connecting the right STN region to both preSMA/SMA and IFGoper and in bilateral tracts connecting preSMA/SMA to IFGoper and the striatum. In addition, significant associations with radial diffusivity (RD) were found in fibers connecting the right preSMA/SMA to striatum and in bilateral tracts between IFGoper and STN region. In our whole-brain analysis, additional significant clusters were identified in the corpus callosum, optic radiation, inferior fronto-occipital tract and white matter of the precentral gyrus. To investigate the relative importance of regional white matter characteristics to response inhibition performance, we performed a step-wise multiple regression analysis that yielded FA in tracts connecting preSMA/SMA to the STN region and striatum, respectively, and RD in fibers connecting IFGoper to the STN region as best predictors of response inhibition performance (42% explained variance). These findings point to a specific contribution of white matter pathways connecting distinct basal ganglia structures with both medial frontal and ventrolateral prefrontal regions to response inhibition.     

Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis

Background: Smaller hippocampal volumes relative to controls are among the most replicated neuroimaging findings in individuals with unipolar but not bipolar depression. Preserved hippocampal volumes in most studies of participants with bipolar disorder may reflect potential neuroprotective effects of lithium (Li). Methods: To investigate hippocampal volumes in patients with bipolar disorder while controlling for Li exposure, we performed a meta-analysis of neuroimaging studies that subdivided patients based on the presence or absence of current Li treatment. To achieve the best coverage of literature, we categorized studies based on whether all or a majority, or whether no or a minority of patients were treated with Li. Hippocampal volumes were compared by combining standardized differences between means (Cohen d) from individual studies using random-effects models. Results: Overall, we analyzed data from 101 patients with bipolar disorder in the Li group, 245 patients in the non-Li group and 456 control participants from 16 studies. Both the left and right hippocampal volumes were significantly larger in the Li group than in controls (Cohen d = 0.53, 95% confidence interval [CI] 0.18 to 0.88; Cohen d = 0.51, 95% CI 0.21 to 0.81, respectively) or the non-Li group (Cohen d = 0.93, 95% CI 0.56 to 1.31; Cohen d = 1.07, 95% CI 0.70 to 1.45, respectively), which had smaller left and right hippocampal volumes than the control group (Cohen d = -0.36, 95% CI -0.55 to -0.17; Cohen d = -0.38, 95% CI -0.63 to -0.13, respectively). There was no evidence of publication bias. Limitations: Missing information about the illness burden or lifetime exposure to Li and polypharmacy in some studies may have contributed to statistical heterogeneity in some analyses. Conclusion: When exposure to Li was minimized, patients with bipolar disorder showed smaller hippocampal volumes than controls or Li-treated patients. Our findings provide indirect support for the negative effects of bipolar disorder on hippocampal volumes and are consistent with the putative neuroprotective effects of Li. The preserved hippocampal volumes among patients with bipolar disorder in most individual studies and all previous meta-analyses may have been related to the inclusion of Li-treated participants.     

Feasibility study of cavitation-induced liposomal doxorubicin release in an AT2 Dunning rat tumor model

Background: Targeted and triggered release of liposomal drug using heat or ultrasound represents a promising treatment modality able to increase the therapeutic-totoxicity ratio of encapsulated drugs. Purpose: To study the ability for high-intensity focused ultrasound to induce liposomal drug release mainly by focused inertial cavitation in vitro and in an animal model. Methods: A 1 MHz ultrasound setup has been developed for in vitro and in vivo drug release from a specific liposomal doxorubicin formulation at a target cavitation dose. Results: Controlled cavitation at 1 MHz was applied within the tumors 48 hours after liposome injection according to preliminary pharmacokinetic study. A small non-significant therapeutic effect of US-liposomal treatment was observed compared to liposomes alone suggesting no beneficial effect of ultrasound in the current setup. Conclusion: The in vitro study provided a suitable ultrasound setup for delivering a cavitation dose appropriate for safe liposomal drug release. However, when converting to an in vivo model, no therapeutic benefit was observed. This may be due to a number of reasons, one of which may be the difficulty in converting in vitro findings to an in vivo model. In light of these findings, we discuss important design features for future studies.     

Mental transformation abilities in patients with unilateral and bilateral vestibular loss

Vestibular information helps to establish a reliable gravitational frame of reference and contributes to the adequate perception of the location of one’s own body in space. This information is likely to be required in spatial cognitive tasks. Indeed, previous studies suggest that the processing of vestibular information is involved in mental transformation tasks in healthy participants. In this study, we investigate whether patients with bilateral or unilateral vestibular loss show impaired ability to mentally transform images of bodies and body parts compared to a healthy, age-matched control group. An egocentric and an object-based mental transformation task were used. Moreover, spatial perception was assessed using a computerized version of the subjective visual vertical and the rod and frame test. Participants with bilateral vestibular loss showed impaired performance in mental transformation, especially in egocentric mental transformation, compared to participants with unilateral vestibular lesions and the control group. Performance of participants with unilateral vestibular lesions and the control group are comparable, and no differences were found between right- and left-sided labyrinthectomized patients. A control task showed no differences between the three groups. The findings from this study substantiate that central vestibular processes are involved in imagined spatial body transformations; but interestingly, only participants with bilateral vestibular loss are affected, whereas unilateral vestibular loss does not lead to a decline in spatial imagery.     

Automation of an algorithm based on fuzzy clustering for analyzing tumoral heterogeneity in human skin carcinoma tissue sections

This study aims to develop a new FT-IR spectral imaging of tumoral tissue permitting a better characterization of tumor heterogeneity and tumor/surrounding tissue interface. Infrared (IR) data were acquired on 13 biopsies of paraffin-embedded human skin carcinomas. Our approach relies on an innovative fuzzy C-means (FCM)-based clustering algorithm, allowing the automatic and simultaneous estimation of the optimal FCM parameters (number of clusters K and fuzziness index m). FCM seems more suitable than classical 'hard' clusterings, as it permits the assignment of each IR spectrum to every cluster with a specific membership value. This characteristic allows differentiating the nuances in the assignment of pixels, particularly those corresponding to tumoral tissue and those located at the tumor/peritumoral tissue interface. FCM images permit to highlight a marked heterogeneity within the tumor and characterize the interconnection between tissular structures. For the infiltrative tumors, a progressive gradient in the membership values of the pixels of the invasive front was also revealed.     

Stereospecific interactions are necessary for Alzheimer disease amyloid-β toxicity

Previous studies suggest membrane binding is a key determinant of amyloid β (Aβ) neurotoxicity. However, it is unclear whether this interaction is receptor driven. To address this issue, a D-handed enantiomer of Aβ42 (D-Aβ42) was synthesized and its biophysical and neurotoxic properties were compared to the wild-type Aβ42 (L-Aβ42). The results showed D- and L-Aβ42 are chemically equivalent with respect to copper binding, generation of reactive oxygen species and aggregation profiles. Cell binding studies show both peptides bound to cultured cortical neurons. However, only L-Aβ42 was neurotoxic and inhibited long term potentiation indicating L-Aβ42 requires a stereospecific target to mediate toxicity. We identified the lipid phosphatidylserine, as a potential target. Annexin V, which has very high affinity for externalized phosphatidylserine, significantly inhibited L-Aβ42 but not D-Aβ42 binding to the cultured cortical neurons and significantly rescued L-Aβ42 neurotoxicity. This suggests that Aβ mediated toxicity in Alzheimer disease is dependent upon Aβ binding to phosphatidylserine on neuronal cells.