Commonalities and Asymmetries in the Neurobiological Infrastructure for Language Production and Comprehension.

The neurobiology of sentence production has been largely understudied compared to the neurobiology of sentence comprehension, due to difficulties with experimental control and motion-related artifacts in neuroimaging. We studied the neural response to constituents of increasing size and specifically focused on the similarities and differences in the production and comprehension of the same stimuli. Participants had to either produce or listen to stimuli in a gradient of constituent size based on a visual prompt. Larger constituent sizes engaged the left inferior frontal gyrus (LIFG) and middle temporal gyrus (LMTG) extending to inferior parietal areas in both production and comprehension, confirming that the neural resources for syntactic encoding and decoding are largely overlapping. An ROI analysis in LIFG and LMTG also showed that production elicited larger responses to constituent size than comprehension and that the LMTG was more engaged in comprehension than production, while the LIFG was more engaged in production than comprehension. Finally, increasing constituent size was characterized by later BOLD peaks in comprehension but earlier peaks in production. These results show that syntactic encoding and parsing engage overlapping areas, but there are asymmetries in the engagement of the language network due to the specific requirements of production and comprehension.

What We said and what I wish We said: Regret during final conversations.

Research indicates that final conversations with dying loved ones are significant but challenging relational events for survivors. Using a qualitative theme analysis, the present study documented survivors' (N = 44) retrospective reports of experiences of regret during final conversations. The analysis revealed experiences of validation regret, intersubjective regret, and encumbrance regret, and the use of regret management techniques. This knowledge is useful because it points to the impetus of regret experienced during final conversations and implicates communication patterns that could negatively impact bereavement.

The effectiveness of weight loss programs for low back pain: a systematic review.

BACKGROUND: Low back pain has been associated with obesity or with being overweight. However, there are no high-quality systematic reviews that have been conducted on the effect of all types of weight loss programs focused on individuals with low back pain. Therefore, the present systematic review aims to evaluate the effectiveness of weight loss programs in reducing back pain and disability or increasing quality of life for individuals experiencing low back pain. MATERIALS AND METHODS: Searches for relevant studies were conducted on CINAHL, Web of Science, Ovid Medline, Ovid Embase and AMED. Studies were included if they were randomized controlled trials, non-randomized studies of intervention or quasi-experimental designs evaluating a weight loss program for persons with low back pain aimed at decreasing back pain and disability. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to evaluate individual studies and GRADE was used to summarize the quality of the evidence. The review was prospectively registered; PROSPERO#: CRD42020196099. RESULTS: Eleven studies (n = 689 participants) including one randomized controlled trial, two non-randomized studies of intervention and eight single-arm studies were included (seven of which evaluated bariatric surgery). There was low-quality evidence that a lifestyle intervention was no better than waitlist for improving back pain and very low-quality evidence from single-arm studies that back pain improved from baseline after bariatric surgery. Most studies included were of poor quality, primarily due to selection bias, uncontrolled confounders, and lack of blinding, limiting the quality of evidence. CONCLUSION: There is very low-quality evidence that weight loss programs may improve back pain, disability, and quality of life in patients with LBP, although adherence and maintenance are potential barriers to implementation.

Laminar specific fMRI reveals directed interactions in distributed networks during language processing.

Interactions between top-down and bottom-up information streams are integral to brain function but challenging to measure noninvasively. Laminar resolution, functional MRI (lfMRI) is sensitive to depth-dependent properties of the blood oxygen level-dependent (BOLD) response, which can be potentially related to top-down and bottom-up signal contributions. In this work, we used lfMRI to dissociate the top-down and bottom-up signal contributions to the left occipitotemporal sulcus (LOTS) during word reading. We further demonstrate that laminar resolution measurements could be used to identify condition-specific distributed networks on the basis of whole-brain connectivity patterns specific to the depth-dependent BOLD signal. The networks corresponded to top-down and bottom-up signal pathways targeting the LOTS during word reading. We show that reading increased the top-down BOLD signal observed in the deep layers of the LOTS and that this signal uniquely related to the BOLD response in other language-critical regions. These results demonstrate that lfMRI can reveal important patterns of activation that are obscured at standard resolution. In addition to differences in activation strength as a function of depth, we also show meaningful differences in the interaction between signals originating from different depths both within a region and with the rest of the brain. We thus show that lfMRI allows the noninvasive measurement of directed interaction between brain regions and is capable of resolving different connectivity patterns at submillimeter resolution, something previously considered to be exclusively in the domain of invasive recordings.

Teaching end-of-life preparation to African Americans.

OBJECTIVE: This is a pilot study with a primary goal to develop an effective, targeted educational intervention that can serve as a teaching tool to educate African American (AA) population, especially the elderly, on options of end of life (EOL) prior to critical care. METHOD: We first assessed the level of preparation for EOL in the AA community through a survey instrument. The survey was used to determine the deficits in knowledge in AA population in Mid-Michigan regarding EOL choices before and after the educational intervention. Paired-sample t-test was used to assess changes in understanding about EOL planning options. Regressions analysis was used to assess these changes while including several demographic covariates. P < 0.05 was considered statistically significant. RESULTS: Our pilot data indicated that the educational intervention could be used as an effective teaching tool in educating AA population on EOL choices. SIGNIFICANCE OF RESULTS: AA patients are more likely to choose life-sustaining measures at the end of their lives compared to other ethnic groups despite terminal illness. This decision is partly based on lack of knowledge of the available options of care at the EOL. Due to multiple life-sustaining measures, the AA patients are not receiving the care to help them peacefully die. This study provides evidence that physicians will need to increase their educational efforts with the AA population to help them better understand EOL options. An educational tool like the one developed in this study may be helpful and lessen the time of education so that the physician can answer any questions at the end of the session and also empower individuals and communities to take an active role in creating a culture of wellness at the EOL and decreasing morbidity.

Speaking in the Brain: The Interaction between Words and Syntax in Sentence Production.

This neuroimaging study investigated the neural infrastructure of sentence-level language production. We compared brain activation patterns, as measured with BOLD-fMRI, during production of sentences that differed in verb argument structures (intransitives, transitives, ditransitives) and the lexical status of the verb (known verbs or pseudoverbs). The experiment consisted of 30 mini-blocks of six sentences each. Each mini-block started with an example for the type of sentence to be produced in that block. On each trial in the mini-blocks, participants were first given the (pseudo-)verb followed by three geometric shapes to serve as verb arguments in the sentences. Production of sentences with known verbs yielded greater activation compared to sentences with pseudoverbs in the core language network of the left inferior frontal gyrus, the left posterior middle temporal gyrus, and a more posterior middle temporal region extending into the angular gyrus, analogous to effects observed in language comprehension. Increasing the number of verb arguments led to greater activation in an overlapping left posterior middle temporal gyrus/angular gyrus area, particularly for known verbs, as well as in the bilateral precuneus. Thus, producing sentences with more complex structures using existing verbs leads to increased activation in the language network, suggesting some reliance on memory retrieval of stored lexical-syntactic information during sentence production. This study thus provides evidence from sentence-level language production in line with functional models of the language network that have so far been mainly based on single-word production, comprehension, and language processing in aphasia.

fMRI Syntactic and Lexical Repetition Effects Reveal the Initial Stages of Learning a New Language.

UNLABELLED: When learning a new language, we build brain networks to process and represent the acquired words and syntax and integrate these with existing language representations. It is an open question whether the same or different neural mechanisms are involved in learning and processing a novel language compared with the native language(s). Here we investigated the neural repetition effects of repeating known and novel word orders while human subjects were in the early stages of learning a new language. Combining a miniature language with a syntactic priming paradigm, we examined the neural correlates of language learning on-line using functional magnetic resonance imaging. In left inferior frontal gyrus and posterior temporal cortex, the repetition of novel syntactic structures led to repetition enhancement, whereas repetition of known structures resulted in repetition suppression. Additional verb repetition led to an increase in the syntactic repetition enhancement effect in language-related brain regions. Similarly, the repetition of verbs led to repetition enhancement effects in areas related to lexical and semantic processing, an effect that continued to increase in a subset of these regions. Repetition enhancement might reflect a mechanism to build and strengthen a neural network to process novel syntactic structures and lexical items. By contrast, the observed repetition suppression points to overlapping neural mechanisms for native and new language constructions when these have sufficient structural similarities. SIGNIFICANCE STATEMENT: Acquiring a second language entails learning how to interpret novel words and relations between words, and to integrate them with existing language knowledge. To investigate the brain mechanisms involved in this particularly human skill, we combined an artificial language learning task with a syntactic repetition paradigm. We show that the repetition of novel syntactic structures, as well as words in contexts, leads to repetition enhancement, whereas repetition of known structures results in repetition suppression. We thus propose that repetition enhancement might reflect a brain mechanism to build and strengthen a neural network to process novel syntactic regularities and novel words. Importantly, the results also indicate an overlap in neural mechanisms for native and new language constructions with sufficient structural similarities.

Spatiotemporal Signatures of Lexical-Semantic Prediction.

Although there is broad agreement that top-down expectations can facilitate lexical-semantic processing, the mechanisms driving these effects are still unclear. In particular, while previous electroencephalography (EEG) research has demonstrated a reduction in the N400 response to words in a supportive context, it is often challenging to dissociate facilitation due to bottom-up spreading activation from facilitation due to top-down expectations. The goal of the current study was to specifically determine the cortical areas associated with facilitation due to top-down prediction, using magnetoencephalography (MEG) recordings supplemented by EEG and functional magnetic resonance imaging (fMRI) in a semantic priming paradigm. In order to modulate expectation processes while holding context constant, we manipulated the proportion of related pairs across 2 blocks (10 and 50% related). Event-related potential results demonstrated a larger N400 reduction when a related word was predicted, and MEG source localization of activity in this time-window (350-450 ms) localized the differential responses to left anterior temporal cortex. fMRI data from the same participants support the MEG localization, showing contextual facilitation in left anterior superior temporal gyrus for the high expectation block only. Together, these results provide strong evidence that facilitatory effects of lexical-semantic prediction on the electrophysiological response 350-450 ms postonset reflect modulation of activity in left anterior temporal cortex.

Disclosures of Cystic Fibrosis-Related Information to Romantic Partners.

In this article, we offer insights into how individuals with cystic fibrosis (CF) share information about their disease with a romantic partner. Using communication privacy management as a sensitizing theoretical construct, four themes emerged following 13 qualitative interviews with persons with CF. Themes about sharing CF-related information with a romantic partner include weighing the risks and benefits of sharing information, the role of health-related triggered rules, the motivations for disclosures, and the reactions from outsiders. Implications of the research suggest a need for more nuanced understandings of how privacy rules are communicated in relationships, how the mismanagement of co-owned information influences future disclosures, how the public-private nature of rare genetic illnesses is managed, and how people with genetic illnesses make disclosure decisions.

Beyond the language given: the neural correlates of inferring speaker meaning.

Even though language allows us to say exactly what we mean, we often use language to say things indirectly, in a way that depends on the specific communicative context. For example, we can use an apparently straightforward sentence like "It is hard to give a good presentation" to convey deeper meanings, like "Your talk was a mess!" One of the big puzzles in language science is how listeners work out what speakers really mean, which is a skill absolutely central to communication. However, most neuroimaging studies of language comprehension have focused on the arguably much simpler, context-independent process of understanding direct utterances. To examine the neural systems involved in getting at contextually constrained indirect meaning, we used functional magnetic resonance imaging as people listened to indirect replies in spoken dialog. Relative to direct control utterances, indirect replies engaged dorsomedial prefrontal cortex, right temporo-parietal junction and insula, as well as bilateral inferior frontal gyrus and right medial temporal gyrus. This suggests that listeners take the speaker's perspective on both cognitive (theory of mind) and affective (empathy-like) levels. In line with classic pragmatic theories, our results also indicate that currently popular "simulationist" accounts of language comprehension fail to explain how listeners understand the speaker's intended message.

Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) is associated with menstrual cycle length changes and, if so, how that compares with those undergoing vaccination or no event (control). METHODS: We conducted a retrospective cohort analysis in which we analyzed prospectively tracked cycle-length data from users of a period tracker application who also responded to a survey regarding COVID-19 symptoms and vaccination. We restricted our sample to users aged 16-45 years, with normal cycle lengths (24-38 days) and regular tracking behavior during the five cycles around COVID-19 symptoms or vaccination or a similar time period for those experiencing no event (control group). We calculated the within-user change in cycle length (days) from the three consecutive cycles preevent average (either vaccination, disease, or neither; cycles 1-3) to the event (cycle 4) and postevent (cycle 5) cycles. We used mixed-effects models to estimate the age- and country-adjusted difference in change in cycle length across the groups. RESULTS: We included 6,514 users from 110 countries representing 32,570 cycles (COVID-19 symptoms: 1,450; COVID-19 vaccination: 4,643; control: 421). The COVID-19 cohort experienced a 1.45-day adjusted increase in cycle length during cycle 4 (COVID-19) compared with their three preevent cycles (95% CI 0.86-2.04). The vaccinated group experienced a 1.14-day adjusted increase in cycle length during cycle 4 (COVID-19 vaccine) compared with their preevent average (95% CI 0.60-1.69). The control group (neither vaccine nor disease) experienced a 0.68-day decrease (95% CI -1.18 to -0.19) in a similar time period. Post hoc tests showed no significant differences in the magnitude of changes between the COVID-19 and vaccination cohorts. In both cohorts, cycle length changes disappeared in the postevent cycle. CONCLUSION: Experiencing COVID-19 is associated with a small change in cycle length similar to COVID-19 vaccination. These changes resolve quickly within the next cycle.

Shared syntax in language production and language comprehension--an FMRI study.

During speaking and listening syntactic processing is a crucial step. It involves specifying syntactic relations between words in a sentence. If the production and comprehension modality share the neuronal substrate for syntactic processing then processing syntax in one modality should lead to adaptation effects in the other modality. In the present functional magnetic resonance imaging experiment, participants either overtly produced or heard descriptions of pictures. We looked for brain regions showing adaptation effects to the repetition of syntactic structures. In order to ensure that not just the same brain regions but also the same neuronal populations within these regions are involved in syntactic processing in speaking and listening, we compared syntactic adaptation effects within processing modalities (syntactic production-to-production and comprehension-to-comprehension priming) with syntactic adaptation effects between processing modalities (syntactic comprehension-to-production and production-to-comprehension priming). We found syntactic adaptation effects in left inferior frontal gyrus (Brodmann's area [BA] 45), left middle temporal gyrus (BA 21), and bilateral supplementary motor area (BA 6) which were equally strong within and between processing modalities. Thus, syntactic repetition facilitates syntactic processing in the brain within and across processing modalities to the same extent. We conclude that that the same neurobiological system seems to subserve syntactic processing in speaking and listening.

A qualitative study of breast cancer treatment decisions: evidence for five decision-making styles.

Being diagnosed with breast cancer requires that women make a number of decisions about their medical treatments. To gain insight into the variety of forces that shape a woman's breast cancer treatment decisions, we conducted semistructured interviews with 44 breast cancer survivors. Through an interpretive analysis, we identified five treatment decision-making styles: (a) medical expert, (b) self-efficacy, (c) relationship embedded, (d) inhibition, and (e) constellation of information, which are differentiated by two dimensions: (a) low versus high information needs and (b) self versus other preferences.

Camphor modulates TRPV3 cation channels activity by interacting with critical pore-region cysteine residues.

TRPV3 ion channels mediate thermo-transduction, nociception, inflammation and dermatitis in mammals. TRPV1-4 proteins have been shown to have conserved cysteine-residues in the pore-forming regions. These residues participate in channel activation via S-nitrosylation of channel proteins. Camphor is a commonly used ligand for TRPV3 channels. Thus the knowledge about the potential binding/interacting site(s) for camphor will help to design effective and potent analgesic compounds. In an overlap-extension PCR method, following primer-pairs were used to mutate conserved cysteine-residues in the pore-region of TRPV3 channels; GATTGAGAATcCTCCAAGGACAAAAAGGAC, TRPV3-C612S-Fw and GTCCTTGGAGgACTTCTCAATCAGTCAGTGAGG, TRPV3-C612S-Rv primers pair. And for TRPV3-C619S: GGACTCcAGTTCCTATGGCCAGC, TRPV3-C619S-Fw and GCTGGCCATAgGAACTGGAGTCC, TRPV3-C619S-Rv respectively. All cDNA constructs were confirmed by DNA-sequencing and used to make cRNAs. Oocytes expressing mTRPV3-C619S and mTRPV3-C612S mutant channels were challenged with 2-APB (1 mM), camphor (10 mM) and dihydrocarveol (10 mM) either at -40 mV or +40 mV holding potentials in voltage-clamp experiments. Responses of both mutants to 2-APB were similar to wild-type mTRPV3. Interestingly, responses to camphor were totally lost in mTRPV3-C619S mutant, while responses to dihydrocarveol remained intact. In contrast mTRPV3-C612S displayed slightly altered (16±2 % reduction) phenotype with respect to camphor sensitivity. It is concluded that pore-region cysteines play critical role in camphor sensitivity of TRPV3 ion channels.

Etiology of Carpal Tunnel Syndrome in a Large Cohort of Children.

(1) Background: Carpal tunnel syndrome (CTS), a compressive mononeuropathy of the median nerve at the wrist, is rare in childhood and occurs most frequently due to secondary causes. (2) Methods: Medical history, electrodiagnostic findings, and imaging data of patients with CTS from two pediatric neuromuscular centers were analyzed retrospectively. The etiology of CTS was investigated and compared with the literature. (3) Results: We report on a cohort of 38 CTS patients (n = 22 females, n = 29 bilateral, mean age at diagnosis 9.8 years). Electrodiagnostic studies of all patients revealed slowing of the antidromic sensory or orthodromic mixed nerve conduction velocities across the carpal tunnel or lack of the sensory nerve action potential and/or prolonged distal motor latencies. Median nerve ultrasound was diagnostic for CTS and confirmed tumorous and vascular malformations. Etiology was secondary in most patients (n = 29; 76%), and mucopolysaccharidosis was the most frequent underlying condition (n = 14; 37%). Idiopathic CTS was rare in this pediatric cohort (n = 9; 24%). (4) Conclusion: Since CTS in childhood is predominantly caused by an underlying disorder, a thorough evaluation and search for a causative condition is recommended in this age group.

No title, no theme: The joined neural space between speakers and listeners during production and comprehension of multi-sentence discourse.

Speakers and listeners usually interact in larger discourses than single words or even single sentences. The goal of the present study was to identify the neural bases reflecting how the mental representation of the situation denoted in a multi-sentence discourse (situation model) is constructed and shared between speakers and listeners. An fMRI study using a variant of the ambiguous text paradigm was designed. Speakers (n = 15) produced ambiguous texts in the scanner and listeners (n = 27) subsequently listened to these texts in different states of ambiguity: preceded by a highly informative, intermediately informative or no title at all. Conventional BOLD activation analyses in listeners, as well as inter-subject correlation analyses between the speakers' and the listeners' hemodynamic time courses were performed. Critically, only the processing of disambiguated, coherent discourse with an intelligible situation model representation involved (shared) activation in bilateral lateral parietal and medial prefrontal regions. This shared spatiotemporal pattern of brain activation between the speaker and the listener suggests that the process of memory retrieval in medial prefrontal regions and the binding of retrieved information in the lateral parietal cortex constitutes a core mechanism underlying the communication of complex conceptual representations.

Impairments in Probabilistic Prediction and Bayesian Learning Can Explain Reduced Neural Semantic Priming in Schizophrenia.

It has been proposed that abnormalities in probabilistic prediction and dynamic belief updating explain the multiple features of schizophrenia. Here, we used electroencephalography (EEG) to ask whether these abnormalities can account for the well-established reduction in semantic priming observed in schizophrenia under nonautomatic conditions. We isolated predictive contributions to the neural semantic priming effect by manipulating the prime's predictive validity and minimizing retroactive semantic matching mechanisms. We additionally examined the link between prediction and learning using a Bayesian model that probed dynamic belief updating as participants adapted to the increase in predictive validity. We found that patients were less likely than healthy controls to use the prime to predictively facilitate semantic processing on the target, resulting in a reduced N400 effect. Moreover, the trial-by-trial output of our Bayesian computational model explained between-group differences in trial-by-trial N400 amplitudes as participants transitioned from conditions of lower to higher predictive validity. These findings suggest that, compared with healthy controls, people with schizophrenia are less able to mobilize predictive mechanisms to facilitate processing at the earliest stages of accessing the meanings of incoming words. This deficit may be linked to a failure to adapt to changes in the broader environment. This reciprocal relationship between impairments in probabilistic prediction and Bayesian learning/adaptation may drive a vicious cycle that maintains cognitive disturbances in schizophrenia.

Syntactic priming in German-English bilinguals during sentence comprehension.

A longstanding question in bilingualism is whether syntactic information is shared between the two language processing systems. We used an fMRI repetition suppression paradigm to investigate syntactic priming in reading comprehension in German-English late-acquisition bilinguals. In comparison to conventional subtraction analyses in bilingual experiments, repetition suppression has the advantage of being able to detect neuronal populations that are sensitive to properties that are shared by consecutive stimuli. In this study, we manipulated the syntactic structure between prime and target sentences. A sentence with a passive sentence structure in English was preceded either by a passive or by an active sentence in English or German. We looked for repetition suppression effects in left inferior frontal, left precentral and left middle temporal regions of interest. These regions were defined by a contrast of all non-target sentences in German and English versus the baseline of sentence-format consonant strings. We found decreases in activity (repetition suppression effects) in these regions of interest following the repetition of syntactic structure from the first to the second language and within the second language. Moreover, a separate behavioural experiment using a word-by-word reading paradigm similar to the fMRI experiment showed faster reading times for primed compared to unprimed English target sentences regardless of whether they were preceded by an English or a German sentence of the same structure. We conclude that there is interaction between the language processing systems and that at least some syntactic information is shared between a bilingual's languages with similar syntactic structures.

Sentence processing is modulated by the current linguistic environment and a priori information: An fMRI study.

INTRODUCTION: Words are not processed in isolation but in rich contexts that are used to modulate and facilitate language comprehension. Here, we investigate distinct neural networks underlying two types of contexts, the current linguistic environment and verb-based syntactic preferences. METHODS: We had two main manipulations. The first was the current linguistic environment, where the relative frequencies of two syntactic structures (prepositional object [PO] and double-object [DO]) would either follow everyday linguistic experience or not. The second concerned the preference toward one or the other structure depending on the verb; learned in everyday language use and stored in memory. German participants were reading PO and DO sentences in German while brain activity was measured with functional magnetic resonance imaging. RESULTS: First, the anterior cingulate cortex (ACC) showed a pattern of activation that integrated the current linguistic environment with everyday linguistic experience. When the input did not match everyday experience, the unexpected frequent structure showed higher activation in the ACC than the other conditions and more connectivity from the ACC to posterior parts of the language network. Second, verb-based surprisal of seeing a structure given a verb (PO verb preference but DO structure presentation) resulted, within the language network (left inferior frontal and left middle/superior temporal gyrus) and the precuneus, in increased activation compared to a predictable verb-structure pairing. CONCLUSION: In conclusion, (1) beyond the canonical language network, brain areas engaged in prediction and error signaling, such as the ACC, might use the statistics of syntactic structures to modulate language processing, (2) the language network is directly engaged in processing verb preferences. These two networks show distinct influences on sentence processing.

Functional MRI reveals evidence of a self-positivity bias in the medial prefrontal cortex during the comprehension of social vignettes.

A large literature in social neuroscience has associated the medial prefrontal cortex (mPFC) with the processing of self-related information. However, only recently have social neuroscience studies begun to consider the large behavioral literature showing a strong self-positivity bias, and these studies have mostly focused on its correlates during self-related judgments and decision-making. We carried out a functional MRI (fMRI) study to ask whether the mPFC would show effects of the self-positivity bias in a paradigm that probed participants' self-concept without any requirement of explicit self-judgment. We presented social vignettes that were either self-relevant or non-self-relevant with a neutral, positive or negative outcome described in the second sentence. In previous work using event-related potentials, this paradigm has shown evidence of a self-positivity bias that influences early stages of semantically processing incoming stimuli. In the present fMRI study, we found evidence for this bias within the mPFC: an interaction between self-relevance and valence, with only positive scenarios showing a self vs other effect within the mPFC. We suggest that the mPFC may play a role in maintaining a positively biased self-concept and discuss the implications of these findings for the social neuroscience of the self and the role of the mPFC.