Perceiving a Stranger's Voice as Being One's Own: A ‘Rubber Voice’ Illusion?

We describe an illusion in which a stranger's voice, when presented as the auditory concomitant of a participant's own speech, is perceived as a modified version of their own voice. When the congruence between utterance and feedback breaks down, the illusion is also broken. Compared to a baseline condition in which participants heard their own voice as feedback, hearing a stranger's voice induced robust changes in the fundamental frequency (F0) of their production. Moreover, the shift in F0 appears to be feedback dependent, since shift patterns depended reliably on the relationship between the participant's own F0 and the stranger-voice F0. The shift in F0 was evident both when the illusion was present and after it was broken, suggesting that auditory feedback from production may be used separately for self-recognition and for vocal motor control. Our findings indicate that self-recognition of voices, like other body attributes, is malleable and context dependent

Multivoxel Patterns Reveal Functionally Differentiated Networks Underlying Auditory Feedback Processing of Speech

Contains fulltext : 122909.pdf (publisher's version ) (Open Access)The everyday act of speaking involves the complex processes of speech motor control. An important component of control is monitoring, detection, and processing of errors when auditory feedback does not correspond to the intended motor gesture. Here we show, using fMRI and converging operations within a multivoxel pattern analysis framework, that this sensorimotor process is supported by functionally differentiated brain networks. During scanning, a real-time speech-tracking system was used to deliver two acoustically different types of distorted auditory feedback or unaltered feedback while human participants were vocalizing monosyllabic words, and to present the same auditory stimuli while participants were passively listening. Whole-brain analysis of neural-pattern similarity revealed three functional networks that were differentially sensitive to distorted auditory feedback during vocalization, compared with during passive listening. One network of regions appears to encode an "error signal" regardless of acoustic features of the error: this network, including right angular gyrus, right supplementary motor area, and bilateral cerebellum, yielded consistent neural patterns across acoustically different, distorted feedback types, only during articulation (not during passive listening). In contrast, a frontotemporal network appears sensitive to the speech features of auditory stimuli during passive listening; this preference for speech features was diminished when the same stimuli were presented as auditory concomitants of vocalization. A third network, showing a distinct functional pattern from the other two, appears to capture aspects of both neural response profiles. Together, our findings suggest that auditory feedback processing during speech motor control may rely on multiple, interactive, functionally differentiated neural systems

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Functional Specialization of the Planum Temporale

The planum temporale (PT) is an anatomically heterogeneous area with several architectonic subdivisions and extensive connections with other parts of the brain. Here I review a functional MRI study investigating the role of a functionally defined area (Spt) within the left PT in speech motor processing and discuss the functional properties of PT regions in the context of findings from recent neurophysiological and neuroimaging studies

Johnsrude IS. Reducing intersubject anatomical variation: Effect of normalization method on sensitivity of functional magnetic resonance imaging data analysis in auditory cortex and the superior temporal region

Abstract Conventional group analysis of functional MRI (fMRI) data usually involves spatial alignment of anatomy across participants by registering every brain image to an anatomical reference image. Due to the high degree of inter-subject anatomical variability, a low-resolution average anatomical model is typically used as the target template, and/or smoothing kernels are applied to the fMRI data to increase the overlap among subjects&apos; image data. However, such smoothing can make it difficult to resolve small regions such as subregions of auditory cortex when anatomical morphology varies among subjects. Here, we use data from an auditory fMRI study to show that using a high-dimensional registration technique (HAMMER) results in an enhanced functional signal-to-noise ratio (fSNR) for functional data analysis within auditory regions, with more localized activation patterns. The technique is validated against DARTEL, a high-dimensional diffeomorphic registration, as well as against commonly used low-dimensional normalization techniques such as the techniques provided with SPM2 (cosine basis functions) and SPM5 (unified segmentation) software packages. We also systematically examine how spatial resolution of the template image and spatial smoothing of the functional data affect the results. Only the high-dimensional technique (HAMMER) appears to be able to capitalize on the excellent anatomical resolution of a single-subject reference template, and, as expected, smoothing increased fSNR, but at the cost of spatial resolution. In general, results demonstrate significant improvement in fSNR using HAMMER * Corresponding author. Address: Medical Image Analysis Laboratory, School of Computing, Queen&apos;s University, Kingston, ON, CANADA. Tel: +1 (613) 533 2797. Email address: [email protected] (Amir M. Tahmasebi ) May 19, 2009 compared to analysis after normalization using DARTEL, or conventional normalization such as cosine basis function and unified segmentation in SPM, with more precisely localized activation foci, at least for activation in the region of auditory cortex. Preprint submitted to NeuroImag

The F0 (Hz) time course for ‘day’ from one representative participant is shown.

<p>This participant was from the Last Mismatch group and assigned V1 as the stimulus voice. The solid purple vertical line at trial 20 indicates the end of the Baseline stage. The two solid red vertical lines indicate the beginning and end of the Stimulus Voice Mismatch stage. The black dashed horizontal line indicates the F0 of the stimulus voice V1.</p

Schematic diagram of the four stages of the experiment.

<p>See text for details.</p