Current evidence strongly suggests that the arcuate fasciculus (AF) is critical for language, from spontaneous speech and word retrieval to repetition and comprehension abilities. However, to further ...pinpoint its unique and differential role in language, its anatomy needs to be explored in greater detail and its contribution to language processing beyond that of known cortical language areas must be established. We address this in a comprehensive evaluation of the specific functional role of the AF in a well-characterized cohort of individuals with chronic aphasia (
n
= 33) following left hemisphere stroke. To evaluate macro- and microstructural integrity of the AF, tractography based on the constrained spherical deconvolution model was performed. The AF in the left and right hemispheres were then manually reconstructed using a modified 3-segment model (
Catani et al., 2005
), and a modified 2-segment model (
Glasser and Rilling, 2008
). The normalized volume and a measure of microstructural integrity of the long and the posterior segments of the AF were significantly correlated with language indices while controlling for gender and lesion volume. Specific contributions of AF segments to language while accounting for the role of specific cortical language areas – inferior frontal, inferior parietal, and posterior temporal – were tested using multiple regression analyses. Involvement of the following tract segments in the left hemisphere in language processing beyond the contribution of cortical areas was demonstrated: the long segment of the AF contributed to naming abilities; anterior segment – to fluency and naming; the posterior segment – to comprehension. The results highlight the important contributions of the AF fiber pathways to language impairments beyond that of known cortical language areas. At the same time, no clear role of the right hemisphere AF tracts in language processing could be ascertained. In sum, our findings lend support to the broader role of the left AF in language processing, with particular emphasis on comprehension and naming, and point to the posterior segment of this tract as being most crucial for supporting residual language abilities.
We investigated the relation between cognitive processing speed and structural properties of white matter pathways via convergent imaging studies in healthy and brain-injured groups. Voxel-based ...morphometry (VBM) was applied to diffusion tensor imaging data from thirty-nine young healthy subjects in order to investigate the relation between processing speed, as assessed with the Digit–Symbol subtest from WAIS-III, and fractional anisotropy, an index of microstructural organization of white matter. Digit–Symbol performance was positively correlated with fractional anisotropy of white matter in the parietal and temporal lobes bilaterally and in the left middle frontal gyrus. Fiber tractography indicated that these regions are consistent with the trajectories of the superior and inferior longitudinal fasciculi. In a second investigation, we assessed the effect of white matter damage on processing speed using voxel-based lesion-symptom mapping (VLSM) analysis of data from seventy-two patients with left-hemisphere strokes. Lesions in left parietal white matter, together with cortical lesions in supramarginal and angular gyri were associated with impaired performance. These findings suggest that cognitive processing speed, as assessed by the Digit–Symbol test, is closely related to the structural integrity of white matter tracts associated with parietal and temporal cortices and left middle frontal gyrus. Further, fiber tractography applied to VBM results and the patient findings suggest that the superior longitudinal fasciculus, a major tract subserving fronto-parietal integration, makes a prominent contribution to processing speed.
Effective defense against natural threats in the environment is essential for the survival of individual animals. Thus, instinctive behavioral responses accompanied by fear have evolved to protect ...individuals from predators and from opponents of the same species (dominant conspecifics). While it has been suggested that all perceived environmental threats trigger the same set of innately determined defensive responses, we tested the alternate hypothesis that different stimuli may evoke differentiable behaviors supported by distinct neural circuitry. The results of behavioral, neuronal immediate early gene activation, lesion, and neuroanatomical experiments indicate that the hypothalamus is necessary for full expression of defensive behavioral responses in a subordinate conspecific, that lesions of the dorsal premammillary nucleus drastically reduce behavioral measures of fear in these animals, and that essentially separate hypothalamic circuitry supports defensive responses to a predator or a dominant conspecific. It is now clear that differentiable neural circuitry underlies defensive responses to fear conditioning associated with painful stimuli, predators, and dominant conspecifics and that the hypothalamus is an essential component of the circuitry for the latter two stimuli.
Category and letter fluency tasks have been used to demonstrate psychological and neurological dissociations between semantic and phonological aspects of word retrieval. Some previous neuroimaging ...and lesion studies have suggested that category fluency (semantic-based word retrieval) is mediated primarily by temporal cortex, while letter fluency (letter-based word retrieval) is mediated primarily by frontal cortex. Other studies have suggested that both letter and category fluency are mediated by frontal cortex. We tested these hypotheses using voxel-based lesion symptom mapping (VLSM) in a group of 48 left-hemisphere stroke patients. VLSM maps revealed that category and letter fluency deficits correlate with lesions in temporal and frontal cortices, respectively. Other regions, including parietal cortex, were significantly implicated in both tasks. Our findings are therefore consistent with the hypothesis that temporal cortex subserves word retrieval constrained by semantics, whereas frontal regions are more critical for strategic word retrieval constrained by phonology.
Early cancer detection is fundamental to the promotion of better health in the community, but disparities remain in the likelihood of cancer being detected at an early stage, some of which relate to ...socio‐demographic factors such as marital status. The aim of this study was to conduct a systematic review of research on the association between marital status and stage at diagnosis of different types of cancer. A comprehensive systematic literature search was run in the Medline and Scopus databases (from January 1990 to June 2014), identifying 245 and 208 articles on PubMed and Scopus respectively. Of these 453 studies, 18 were judged eligible for this systematic review. A quality assessment was performed on the studies using the 22 items in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. This review confirmed the important influence of being married on the earlier detection of cancer. None of the studies considered identified more cases of cancer in a later stage among married patients, and the majority of them reported a statically significant association between marital status and stage at diagnosis, with a positive effect of marriage on the likelihood of cancer being diagnosed at an early stage, for various types of malignancy. In particular, our meta‐analysis showed that the unmarried have higher odds of having a later stage of breast cancer (OR = 1.287 95% CI: 1.025–1.617) or melanoma (OR = 1.350 95% CI: 1.161–1.570) at diagnosis. Specific interventions should be developed for the unmarried population to improve their chances of any neoplasms being diagnosed at an early stage, thereby reducing health disparities in the population at large.
Previous studies have documented temporal attraction in perceived times of actions and their effects. While some authors argue that voluntary action is a necessary condition for this phenomenon, ...others claim that the causal relationship between action and effect is the crucial ingredient. In the present study, we investigate voluntary action and causality as the necessary and sufficient conditions for temporal binding. We used a variation of the launching effect proposed by Michotte, in which participants controlled the launch stimulus in some blocks. Volunteers reported causality ratings and estimated the interval between the two events. Our results show dissociations between causality ratings and temporal estimation. While causality ratings are not affected by voluntary action, temporal bindings were only found in the presence of both voluntary action and high causality. Our results indicate that voluntary action and causality are both necessary for the emergence of temporal binding.
In the early stages of the COVID-19 global pandemic, caused by the SARS-CoV-2 virus, low- and middle-income countries (LMICs) appeared to be experiencing lower morbidity and mortality rates than ...high-income countries, particularly the United States. Various suggestions put forward to account for this included the possibility that LMICs might be experiencing off-target benefits of infant vaccination with BCG, intended primarily to protect against tuberculosis. A number of ecologic epidemiological studies that considered COVID-19 morbidity and mortality rates across countries appeared to support this suggestion. Ecologic studies, however, are primarily hypothesis-generating, given their well-known limitations in extrapolating to the individual-person level. The present study, which employed anonymized records of U.S. Military Veterans treated by the Department of Veterans Affairs was principally a case-control study of COVID-19 infections with a retrospective cohort study of mortality nested within the infections. Controls were a random sample of Veterans not recorded as having had COVID-19. There were 263,039 controls and 167,664 COVID-19 cases, of whom 5,016 died. The combination of country and year of birth was used as a surrogate for infant BCG vaccination. The study did not support the hypothesis that BCG in infancy was protective against COVID-19. The odds ratio for infection was 1.07 (95% confidence interval CI: 1.03, 1.11) and the risk ratio for mortality among the COVID-19 cases was 0.86 (95% CI: 0.63, 1.18). The potential for non-differential exposure misclassification was a concern, possibly biasing measures of association toward the null value.
Low- and middle-income countries (LMICs) have appeared to be much less affected by the COVID-19 pandemic, caused by the SARS-CoV-2 virus, than might have been expected from the effects of the virus in more-developed countries. It has been suggested that BCG vaccination of infants against tuberculosis in LMICs might be providing cross-protection against COVID-19. BCG has never been routinely administered in the United States and is not currently administered in most other developed countries.
Some epidemiology studies, known as "ecologic" studies have provided support for the idea that BCG is protecting against COVID-19. However, ecologic studies, with group (i.e., country) measures of exposure and health outcomes, are difficult to interpret in terms of cause and effect.
More interpretable are studies that use individual-person measures of exposure and health outcome. We carried out such a study using data from several hundred-thousand U.S. military Veterans, many of whom were born in LMICs and would have received BCG vaccination as infants. Many U.S. Veterans have had COVID-19, and many of those have died of it.
Our study, the first of its kind, found no evidence to support the idea that infant BCG vaccination protects against infection or death from COVID-19.
Italy implemented two-dose universal varicella vaccination (UVV) regionally from 2003 to 2013 and nationally from 2017 onwards. Our objective was to analyze regional disparities in varicella outcomes ...resulting from disparities in vaccine coverage rates (VCRs) projected over a 50-year time-horizon (2020-2070). A previously published dynamic transmission model was updated to quantify the potential public health impact of the UVV program in Italy at the national and regional levels. Four 2-dose vaccine strategies utilizing monovalent (V) and quadrivalent (MMRV) vaccines were evaluated for each region: (A) MMRV-MSD/MMRV-MSD, (B) MMRV-GSK/MMRV-GSK, (C) V-MSD/MMRV-MSD, and (D) V-GSK/MMRV-GSK. Costs were reported in 2022 Euros. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually. Under strategy A, the three regions with the lowest first-dose VCR reported increased varicella cases (+ 34.3%), hospitalizations (+ 20.0%), QALYs lost (+ 5.9%), payer costs (+ 22.2%), and societal costs (+ 14.6%) over the 50-year time-horizon compared to the three regions with highest first-dose VCR. Regions with low first-dose VCR were more sensitive to changes in VCR than high first-dose VCR regions. Results with respect to second-dose VCR were qualitatively similar, although smaller in magnitude. Results were similar across all vaccine strategies.
Maternal aggression is under the control of a wide variety of factors that prime the females for aggression or trigger the aggressive event. Maternal attacks are triggered by the perception of ...sensory cues from the intruder, and here we have identified a site in the hypothalamus of lactating rats that is highly responsive to the male intruder—the ventral premammillary nucleus (PMv). The PMv is heavily targeted by the medial amygdalar nucleus, and we used lesion and immediate-early gene studies to test our working hypothesis that the PMv signals the presence of a male intruder and transfers this information to the network organizing maternal aggression. PMv-lesioned dams exhibit significantly reduced maternal aggression, without affecting maternal care. The Fos analysis revealed that PMv influences the activation of hypothalamic and septal sites shown to be mobilized during maternal aggression, including the medial preoptic nucleus (likely to represent an important locus to integrate priming stimuli critical for maternal aggression), the caudal two-thirds of the hypothalamic attack area (comprising the ventrolateral part of the ventromedial hypothalamic nucleus and the adjacent tuberal region of the lateral hypothalamic area, critical for the expression of maternal aggression), and the ventral part of the anterior bed nuclei of the stria terminalis (presently discussed as being involved in controlling neuroendocrine and autonomie responses accompanying maternal aggression). These findings reveal an important role for the PMv in detecting the male intruder and how this nucleus modulates the network controlling maternal aggression.
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