Contextual Influences on Phonetic Categorization in School-Aged Children

Perceptual stability in adult listeners is supported by the ability to process acoustic-phonetic variation categorically and dynamically adjust category boundaries given systematic contextual influences. The current study examined the developmental trajectory of such flexibility. Adults and school-aged children (5–10 years of age) made voicing identification decisions to voice-onset-time (VOT) continua that differed in speaking rate and place of articulation. The results showed that both populations were sensitive to contextual influences; the voicing boundary was located at a longer VOT for the slow compared to the fast speaking rate continuum and for the velar compared to the labial continuum, and the magnitude of the displacement was slighter greater for the adults compared to the children. Moreover, the two populations differed in terms of the absolute location of the voicing boundaries and the categorization slopes, with slopes becoming more categorical as age increased. These results demonstrate that sensitivity to contextual influences on speech perception emerges early in development, but mature perceptual tuning requires extended experience

Using TMS to evaluate a causal role for right posterior temporal cortex in talker-specific phonetic processing

Available online 21 April 2023Theories suggest that speech perception is informed by listeners’ beliefs of what phonetic variation is typical of a talker. A previous fMRI study found right middle temporal gyrus (RMTG) sensitivity to whether a phonetic variant was typical of a talker, consistent with literature suggesting that the right hemisphere may play a key role in conditioning phonetic identity on talker information. The current work used transcranial magnetic stimulation (TMS) to test whether the RMTG plays a causal role in processing talker-specific phonetic variation. Listeners were exposed to talkers who differed in how they produced voiceless stop consonants while TMS was applied to RMTG, left MTG, or scalp vertex. Listeners subsequently showed near-ceiling performance in indicating which of two variants was typical of a trained talker, regardless of previous stimulation site. Thus, even though the RMTG is recruited for talker-specific phonetic processing, modulation of its function may have only modest consequences.This research was supported by NSF 1554810 (PI: EBM), NIH NIDCD 2R01 DC013064 (PI: EBM) and NSF NRT 1747486 (PI: JSM). This research was supported in part by the Basque Government through the BERC 2022–2025 program, by the Spanish State Research Agency through BCBL Severo Ochoa excellence accreditation CEX2020-001010- S and award PID2020-119131 GB-I000

Diminished Effort on a Progressive Ratio Task in Both Unipolar and Bipolar Depression

Background Amotivation, or decisional anhedonia, is a prominent and disabling feature of depression. However, this aspect of depression remains understudied, and no prior work has applied objective laboratory tests of motivation in both unipolar and bipolar depression. Methods We assessed motivation deficits using a Progressive Ratio Task (PRT) that indexes willingness to exert effort for monetary reward. The PRT was administered to 96 adults ages 18–60 including 25 participants with a current episode of unipolar depression, 28 with bipolar disorder (current episode depressed), and 43 controls without any Axis I psychiatric disorders. Results Depressed participants exhibited significantly lower motivation than control participants as objectively defined by progressive ratio breakpoints. Both the unipolar and bipolar groups were lower than controls but did not differ from each other. Limitations Medication use differed across groups, and we did not have a separate control task to measure psychomotor activity; however neither medication effects or psychomotor slowing are likely to explain our findings. Conclusions Our study fills an important gap in the literature by providing evidence that diminished effort on the PRT is present across depressed patients who experience either unipolar or bipolar depression. This adds to growing evidence for shared mechanisms of reward and motivation dysfunction, and highlights the importance of improving the assessment and treatment of motivation deficits across the mood disorders spectrum

Variation in Long-Term Acute Care Hospital Use After Intensive Care

Long-term acute care hospitals (LTACs) are an increasingly common discharge destination for patients recovering from intensive care. In this article the authors use U.S. Medicare claims data to examine regional- and hospital-level variation in LTAC utilization after intensive care to determine factors associated with their use. Using hierarchical regression models to control for patient characteristics, this study found wide variation in LTAC utilization across hospitals, even controlling for LTAC access within a region. Several hospital characteristics were independently associated with increasing LTAC utilization, including increasing hospital size, for-profit ownership, academic teaching status, and colocation of the LTAC within an acute care hospital. These findings highlight the need for research into LTAC admission criteria and the incentives driving variation in LTAC utilization across hospitals

Development and Validation of the Microbiology for Health Sciences Concept Inventory

Identifying misconceptions in student learning is a valuable practice for evaluating student learning gains and directing educational interventions. By accurately identifying students’ knowledge and misconceptions about microbiology concepts, instructors can design effective classroom practices centered on student understanding. Following the development of ASM’s Curriculum Guidelines in 2012, we developed a concept inventory, the Microbiology for Health Sciences Concept Inventory (MHSCI), that measures learning gains and identifies student misconceptions in health sciences microbiology classrooms. The 23-question MHSCI was delivered to a wide variety of students at multiple institution types. Psychometric analysis identified that the MHSCI instrument is both discriminatory and reliable in measuring student learning gains. The MHSCI results correlated with course outcomes, showing the value of using the instrument alongside course level assessments to measure student learning. The MHSCI is a reliable and efficient way to measure student learning in microbiology and can be used both as a faculty development tool and an effective student assessment tool

Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children DMN in children with ASD

AbstractFunctional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8–13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core—medial prefrontal cortex–posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD

Evolutionary history of anglerfishes (Teleostei: Lophiiformes): a mitogenomic perspective

<p>Abstract</p> <p>Background</p> <p>The teleost order Lophiiformes, commonly known as the anglerfishes, contains a diverse array of marine fishes, ranging from benthic shallow-water dwellers to highly modified deep-sea midwater species. They comprise 321 living species placed in 68 genera, 18 families and 5 suborders, but approximately half of the species diversity is occupied by deep-sea ceratioids distributed among 11 families. The evolutionary origins of such remarkable habitat and species diversity, however, remain elusive because of the lack of fresh material for a majority of the deep-sea ceratioids and incompleteness of the fossil record across all of the Lophiiformes. To obtain a comprehensive picture of the phylogeny and evolutionary history of the anglerfishes, we assembled whole mitochondrial genome (mitogenome) sequences from 39 lophiiforms (33 newly determined during this study) representing all five suborders and 17 of the 18 families. Sequences of 77 higher teleosts including the 39 lophiiform sequences were unambiguously aligned and subjected to phylogenetic analysis and divergence time estimation.</p> <p>Results</p> <p>Partitioned maximum likelihood analysis confidently recovered monophyly for all of the higher taxa (including the order itself) with the exception of the Thaumatichthyidae (<it>Lasiognathus </it>was deeply nested within the Oneirodidae). The mitogenomic trees strongly support the most basal and an apical position of the Lophioidei and a clade comprising Chaunacoidei + Ceratioidei, respectively, although alternative phylogenetic positions of the remaining two suborders (Antennarioidei and Ogcocephaloidei) with respect to the above two lineages are statistically indistinguishable. While morphology-based intra-subordinal relationships for relatively shallow, benthic dwellers (Lophioidei, Antennarioidei, Ogcocephaloidei, Chaunacoidei) are either congruent with or statistically indistinguishable from the present mitogenomic tree, those of the principally deep-sea midwater dwellers (Ceratioidei) cannot be reconciled with the molecular phylogeny. A relaxed molecular-clock Bayesian analysis of the divergence times suggests that all of the subordinal diversifications have occurred during a relatively short time period between 100 and 130 Myr ago (early to mid Cretaceous).</p> <p>Conclusions</p> <p>The mitogenomic analyses revealed previously unappreciated phylogenetic relationships among the lophiiform suborders and ceratioid familes. Although the latter relationships cannot be reconciled with the earlier hypotheses based on morphology, we found that simple exclusion of the reductive or simplified characters can alleviate some of the conflict. The acquisition of novel features, such as male dwarfism, bioluminescent lures, and unique reproductive modes allowed the deep-sea ceratioids to diversify rapidly in a largely unexploited, food-poor bathypelagic zone (200-2000 m depth) relative to the other lophiiforms occurring in shallow coastal areas.</p

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB