Empathic brain responses in insula are modulated by levels of alexithymia but not autism

Difficulties in social cognition are well recognized in individuals with autism spectrum conditions (henceforth ‘autism'). Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism, much less is known about the capacity of individuals with autism for affect sharing. Based on previous data suggesting that empathy deficits in autism are a function of interoceptive deficits related to alexithymia, we aimed to investigate empathic brain responses in autistic and control participants with high and low degrees of alexithymia. Using functional magnetic resonance imaging, we measured empathic brain responses with an ‘empathy for pain' paradigm assessing empathic brain responses in a real-life social setting that does not rely on attention to, or recognition of, facial affect cues. Confirming previous findings, empathic brain responses to the suffering of others were associated with increased activation in left anterior insula and the strength of this signal was predictive of the degree of alexithymia in both autistic and control groups but did not vary as a function of group. Importantly, there was no difference in the degree of empathy between autistic and control groups after accounting for alexithymia. These findings suggest that empathy deficits observed in autism may be due to the large comorbidity between alexithymic traits and autism, rather than representing a necessary feature of the social impairments in autis

Financing transformative health systems towards achievement of the health Sustainable Development Goals: a model for projected resource needs in 67 low-income and middle-income countries

The ambitious development agenda of the Sustainable Development Goals (SDGs) requires substantial investments across several sectors, including for SDG 3 (healthy lives and wellbeing). No estimates of the additional resources needed to strengthen comprehensive health service delivery towards the attainment of SDG 3 and universal health coverage in low-income and middle-income countries have been published. Methods We developed a framework for health systems strengthening, within which population-level and individual-level health service coverage is gradually scaled up over time. We developed projections for 67 low-income and middle-income countries from 2016 to 2030, representing 95% of the total population in low-income and middle-income countries. We considered four service delivery platforms, and modelled two scenarios with differing levels of ambition: a progress scenario, in which countries' advancement towards global targets is constrained by their health system's assumed absorptive capacity, and an ambitious scenario, in which most countries attain the global targets. We estimated the associated costs and health effects, including reduced prevalence of illness, lives saved, and increases in life expectancy. We projected available funding by country and year, taking into account economic growth and anticipated allocation towards the health sector, to allow for an analysis of affordability and financial sustainability. Findings We estimate that an additional $274 billion spending on health is needed per year by 2030 to make progress towards the SDG 3 targets (progress scenario), whereas US$371 billion would be needed to reach health system targets in the ambitious scenario—the equivalent of an additional $41 (range 15–102) or$58 (22–167) per person, respectively, by the final years of scale-up. In the ambitious scenario, total health-care spending would increase to a population-weighted mean of $271 per person (range 74–984) across country contexts, and the share of gross domestic product spent on health would increase to a mean of 7·5$20–54 billion per year is projected. Should funds be made available and used as planned, the ambitious scenario would save 97 million lives and significantly increase life expectancy by 3·1–8·4 years, depending on the country profile. Interpretation All countries will need to strengthen investments in health systems to expand service provision in order to reach SDG 3 health targets, but even the poorest can reach some level of universality. In view of anticipated resource constraints, each country will need to prioritise equitably, plan strategically, and cost realistically its own path towards SDG 3 and universal health coverage

They played with the trade: MEG investigation of the processing of past tense verbs and their phonological twins

How regular and irregular verbs are processed remains a matter of debate. Some English-speaking patients with nonfluent aphasia are especially impaired on regular past-tense forms like played, whether the task requires production, comprehension or even the judgement that "play" and "played" sound different. Within a dual-mechanism account of inflectional morphology, these deficits reflect disruption to the rule-based process that adds (or strips) the suffix -ed to regular verb stems; but the fact that the patients are also impaired at detecting the difference between word pairs like "tray" and "trade" (the latter being a phonological but not a morphological twin to "played") suggests an important role for phonological characteristics of the regular past tense. The present study examined MEG brain responses in healthy participants evoked by spoken regular past-tense forms and phonological twin words (plus twin pseudowords and a non-speech control) presented in a passive oddball paradigm. Deviant forms (played, trade, kwade/kwayed) relative to their standards (play, tray, kway) elicited a pronounced neuromagnetic response at approximately 130 ms after the onset of the affix; this response was maximal at sensors over temporal areas of both hemispheres but stronger on the left, especially for played and kwayed. Relative to the same standards, a different set of deviants ending in /t/--plate, trait and kwate--produced stronger difference responses especially over the right hemisphere. Results are discussed with regard to dual- and single-mechanism theories of past tense processing and the need to consider neurobiological evidence in attempts to understand inflectional morphology

Effect of Divalent Cations on DMPC/DHPC Bicelle Formation and Alignment

Many important classes of biomolecules require divalent cations for optimal activity, making these ions essential for biologically relevant structural studies. Bicelle mixtures composed of short-chain and long-chain lipids are often used in solution- and solid-state NMR structure determination; however, the phase diagrams of these useful orienting media and membrane mimetics are sensitive to other solution components. Therefore, we have investigated the effect of varying concentrations of four divalent cations, Ca²⁺, Mg²⁺, Zn²⁺, and Cd²⁺, on cholesterol sulfate-stabilized DMPC/DHPC bicelles. We found that low concentrations of all the divalent ions are tolerated with minimal perturbation. At higher concentrations Zn²⁺ and Cd²⁺ disrupt the magnetically aligned phase while Ca²⁺ and Mg²⁺ produce more strongly oriented phases. This result indicates that divalent cations are not only required to maintain the biological activity of proteins and nucleic acids; they may also be used to manipulate the behavior of the magnetically aligned phase

Atypical recruitment of medial prefrontal cortex in autism spectrum disorders:an fMRI study of two executive function tasks

AbstractRecent studies have suggested an uneven profile of executive dysfunction in autism spectrum disorders (ASD). For example, some authors have reported deficits on newly developed tests of executive function sensitive to rostral prefrontal function, despite spared, or even superior, performance on other tests. We investigated the performance of a group of high-functioning participants with ASD (N=15) and an age- and IQ-matched control group (N=18) on two executive function tests, whilst undergoing functional magnetic resonance imaging (fMRI). Behaviourally, there were no significant differences between the two groups. In a classical test of executive function (random response generation), BOLD signal differed between the groups in the cerebellum but not in the frontal lobes. However, on a new test of executive function (selection between stimulus-oriented and stimulus-independent thought), the ASD group exhibited significantly greater signal-change in medial rostral prefrontal cortex (especially Brodmann Area 10) in the comparison of stimulus-oriented versus stimulus-independent attention. In addition, the new test (but not the classical test) provided evidence for abnormal functional organisation of medial prefrontal cortex in ASD. These results underline the heterogeneity of different tests of executive function, and suggest that executive functioning in ASD is associated with task-specific functional change

Preferential and Specific Binding of Human αB-Crystallin to a Cataract-Related Variant of γS-Crystallin

Transparency in the eye lens is maintained via specific, functional interactions among the structural βγ- and chaperone α-crystallins. Here, we report the structure and α-crystallin binding interface of the G18V variant of human γS-crystallin (γS-G18V), which is linked to hereditary childhood-onset cortical cataract. Comparison of the solution nuclear magnetic resonance structures of wild-type and G18V γS-crystallin, both presented here, reveal that the increased aggregation propensity of γS-G18V results from neither global misfolding nor the solvent exposure of a hydrophobic residue but instead involves backbone rearrangement within the N-terminal domain. αB-crystallin binds more strongly to the variant, via a well-defined interaction surface observed via chemical shift differences. In the context of the αB-crystallin structure and the finding that it forms heterogeneous multimers, our structural studies suggest a potential mechanism for cataract formation via the depletion of the finite αB-crystallin population of the lens

Levels of emotional awareness and autism: an fMRI study

Autism is associated with an inability to identify and distinguish one’s own feelings. We assessed this inability using alexithymia and empathy questionnaires, and used fMRI to investigate brain activity while introspecting on emotion. Individuals with high functioning autism/Asperger syndrome (HFA/AS) were compared with matched controls. Participants rated stimuli from the International Affective Picture System twice, once according to the degree of un/pleasantness that the pictures induced, and once according to their color balance. The groups differed significantly on both alexithymia and empathy questionnaires. Alexithymia and lack of empathy were correlated, indicating a link between understanding one’s own and others’ emotions. For both groups a strong relationship between questionnaire scores and brain activity was found in the anterior insula (AI), when participants were required to assess their feelings to unpleasant pictures. Regardless of selfreported degree of emotional awareness, individuals with HFA/AS differed from controls when required to introspect on their feelings by showing reduced activation in self-reflection/mentalizing regions. Thus, we conclude that difficulties in emotional awareness are related to hypoactivity in AI in both individuals with HFA/AS and controls, and that the particular difficulties in emotional awareness in individuals with HFA/AS are not related to their impairments in selfreflection/mentalizing