Selective spatial attention in lateralized multi-talker speech perception: EEG correlates and the role of age.

Speech comprehension under dynamic cocktail party conditions requires auditory search for relevant speech content and focusing spatial attention on the target talker. Here, we investigated the development of these cognitive processes in a population of 329 participants aged 20-70 years. We used a multi-talker speech detection and perception task in which pairs of words (each consisting of a cue and a target word) were simultaneously presented from lateralized positions. Participants attended to predefined cue words and responded to the corresponding target. Task difficulty was varied by presenting cue and target stimuli at different intensity levels. Decline in performance was observed only in the oldest group (age range 53-70 years) and only in the most difficult condition. The EEG analysis of neurocognitive correlates of lateralized auditory attention and stimulus evaluation (N2ac, LPCpc, alpha power lateralization) revealed age-associated changes in focussing on and processing of task-relevant information, while no such deficits were found on early auditory search and target segregation. Irrespective of age, more challenging listening conditions were associated with an increased allocation of attentional resources.

Using electronic health record data to link families: an illustrative example using intergenerational patterns of obesity.

OBJECTIVE: Electronic health record (EHR) data are a valuable resource for population health research but lack critical information such as relationships between individuals. Emergency contacts in EHRs can be used to link family members, creating a population that is more representative of a community than traditional family cohorts. MATERIALS AND METHODS: We revised a published algorithm: relationship inference from the electronic health record (RIFTEHR). Our version, Pythonic RIFTEHR (P-RIFTEHR), identifies a patient's emergency contacts, matches them to existing patients (when available) using network graphs, checks for conflicts, and infers new relationships. P-RIFTEHR was run on December 15, 2021 in the Northwestern Medicine Electronic Data Warehouse (NMEDW) on approximately 2.95 million individuals and was validated using the existing link between children born at NM hospitals and their mothers. As proof-of-concept, we modeled the association between parent and child obesity using logistic regression. RESULTS: The P-RIFTEHR algorithm matched 1 157 454 individuals in 448 278 families. The median family size was 2, the largest was 32 persons, and 247 families spanned 4 generations or more. Validation of the mother-child pairs resulted in 95.1% sensitivity. Children were 2 times more likely to be obese if a parent is obese (OR: 2.30; 95% CI, 2.23-2.37). CONCLUSION: P-RIFTEHR can identify familiar relationships in a large, diverse population in an integrated health system. Estimates of parent-child inheritability of obesity using family structures identified by the algorithm were consistent with previously published estimates from traditional cohort studies.

Cross-modal interactions at the audiovisual cocktail-party revealed by behavior, ERPs, and neural oscillations.

Theories of attention argue that objects are the units of attentional selection. In real-word environments such objects can contain visual and auditory features. To understand how mechanisms of selective attention operate in multisensory environments, in this pre-registered study, we created an audiovisual cocktail-party situation, in which two speakers (left and right of fixation) simultaneously articulated brief numerals. In three separate blocks, informative auditory speech was presented (a) alone or paired with (b) congruent or (c) uninformative visual speech. In all blocks, subjects localized a pre-defined numeral. While audiovisual-congruent and uninformative speech improved response times and speed of information uptake according to diffusion modeling, an ERP analysis revealed that this did not coincide with enhanced attentional engagement. Yet, consistent with object-based attentional selection, the deployment of auditory spatial attention (N2ac) was accompanied by visuo-spatial attentional orienting (N2pc) irrespective of the informational content of visual speech. Notably, an N2pc component was absent in the auditory-only condition, demonstrating that a sound-induced shift of visuo-spatial attention relies on the availability of audio-visual features evolving coherently in time. Additional exploratory analyses revealed cross-modal interactions in working memory and modulations of cognitive control.

Attentional modulations of alpha power are sensitive to the task-relevance of auditory spatial information.

The topographical distribution of oscillatory power in the alpha band is known to vary depending on the current focus of spatial attention. Here, we investigated to what extend univariate and multivariate measures of post-stimulus alpha power are sensitive to the required spatial specificity of a task. To this end, we varied the perceptual load and the spatial demand in an auditory search paradigm. A centrally presented sound at the beginning of each trial indicated the to-be-localized target sound. This spatially unspecific pre-cue was followed by a sound array, containing either two (low perceptual load) or four (high perceptual load) simultaneously presented lateralized sound stimuli. In separate task blocks, participants were instructed either to report whether the target was located on the left or the right side of the sound array (low spatial demand) or to indicate the exact target location (high spatial demand). Univariate alpha lateralization magnitude was neither affected by perceptual load nor by spatial demand. However, an analysis of onset latencies revealed that alpha lateralization emerged earlier in low (vs high) perceptual load trials as well as in low (vs high) spatial demand trials. Finally, we trained a classifier to decode the specific target location based on the multivariate alpha power scalp topography. A comparison of decoding accuracy in the low and high spatial demand conditions suggests that the amount of spatial information present in the scalp distribution of alpha-band power increases as the task demands a higher degree of spatial specificity. Altogether, the results offer new insights into how the dynamic adaption of alpha-band oscillations in response to changing task demands is associated with post-stimulus attentional processing.

Zero-Bias Power-Detector Circuits based on MoS2 Field-Effect Transistors on Wafer-Scale Flexible Substrates.

The design, fabrication, and characterization of wafer-scale, zero-bias power detectors based on 2D MoS2 field-effect transistors (FETs) are demonstrated. The MoS2 FETs are fabricated using a wafer-scale process on 8 µm-thick polyimide film, which, in principle, serves as a flexible substrate. The performances of two chemical vapor deposition MoS2 sheets, grown with different processes and showing different thicknesses, are analyzed and compared from the single device fabrication and characterization steps to the circuit level. The power-detector prototypes exploit the nonlinearity of the transistors above the cut-off frequency of the devices. The proposed detectors are designed employing a transistor model based on measurement results. The fabricated circuits operate in the Ku-band between 12 and 18 GHz, with a demonstrated voltage responsivity of 45 V W-1 at 18 GHz in the case of monolayer MoS2 and 104 V W-1 at 16 GHz in the case of multilayer MoS2 , both achieved without applied DC bias. They are the best-performing power detectors fabricated on flexible substrate reported to date. The measured dynamic range exceeds 30 dB, outperforming other semiconductor technologies like silicon complementary metal-oxide-semiconductor circuits and GaAs Schottky diodes.

Do congruent lip movements facilitate speech processing in a dynamic audiovisual multi-talker scenario? An ERP study with older and younger adults.

In natural conversations, visible mouth and lip movements play an important role in speech comprehension. There is evidence that visual speech information improves speech comprehension, especially for older adults and under difficult listening conditions. However, the neurocognitive basis is still poorly understood. The present EEG experiment investigated the benefits of audiovisual speech in a dynamic cocktail-party scenario with 22 (aged 20-34 years) younger and 20 (aged 55-74 years) older participants. We presented three simultaneously talking faces with a varying amount of visual speech input (still faces, visually unspecific and audiovisually congruent). In a two-alternative forced-choice task, participants had to discriminate target words ("yes" or "no") among two distractors (one-digit number words). In half of the experimental blocks, the target was always presented from a central position, in the other half, occasional switches to a lateral position could occur. We investigated behavioral and electrophysiological modulations due to age, location switches and the content of visual information, analyzing response times and accuracy as well as the P1, N1, P2, N2 event-related potentials (ERPs) and the contingent negative variation (CNV) in the EEG. We found that audiovisually congruent speech information improved performance and modulated ERP amplitudes in both age groups, suggesting enhanced preparation and integration of the subsequent auditory input. In the older group, larger amplitude measures were found in early phases of processing (P1-N1). Here, amplitude measures were reduced in response to audiovisually congruent stimuli. In later processing phases (P2-N2) we found decreased amplitude measures in the older group, while an amplitude reduction for audiovisually congruent compared to visually unspecific stimuli was still observable. However, these benefits were only observed as long as no location switches occurred, leading to enhanced amplitude measures in later processing phases (P2-N2). To conclude, meaningful visual information in a multi-talker setting, when presented from the expected location, is shown to be beneficial for both younger and older adults.

EEG correlates of spatial shifts of attention in a dynamic multi-talker speech perception scenario in younger and older adults.

Speech perception under "cocktail-party" conditions critically depends on the focusing of attention toward the talker of interest. In dynamic auditory scenes, changes in talker settings require rapid shifts of attention, which is especially relevant when the position of a target talker switches from one location to another. Here, we explored electrophysiological correlates of shifts in spatial auditory attention, using a free-field speech perception task, in which sequences of short words (a company name, followed by a numeric value, e.g., "Bosch-6") were presented in the participants' left and right horizontal plane. Younger and older participants responded to the value of a pre-defined target company, while ignoring three simultaneously presented pairs of concurrent company names and values from different locations. All four stimulus pairs were spoken by different talkers, alternating from trial-to-trial. The location of the target company was within either the left or right hemisphere for a variable number of consecutive trials (between 3 and 42 trials) and then changed, switching from the left to the right hemispace or vice versa. Thus, when a switch occurred, the participants had to search for the new position of the target company among the concurrent streams of auditory information and re-focus their attention on the relevant location. As correlates of lateralized spatial auditory attention, the anterior contralateral N2 subcomponent (N2ac) and the posterior alpha power lateralization were analyzed in trials immediately before and after switches of the target location. Both measures were increased after switches, while only the increase in N2ac was related to better speech perception performance (i.e., a reduced post-switch decline in accuracy). While both age groups showed a similar pattern of switch-related attentional modulations, N2ac and alpha lateralization to the task-relevant stimulus (the target company's value) was overall greater in the younger, than older, group. The results suggest that N2ac and alpha lateralization reflect different attentional processes in multi-talker speech perception, the first being primarily associated with auditory search and the focusing of attention, and the second with the in-depth attentional processing of task-relevant information. Especially the second process appears to be prone to age-related cognitive decline.

A dual mechanism underlying retroactive shifts of auditory spatial attention: dissociating target- and distractor-related modulations of alpha lateralization.

Attention can be allocated to mental representations to select information from working memory. To date, it remains ambiguous whether such retroactive shifts of attention involve the inhibition of irrelevant information or the prioritization of relevant information. Investigating asymmetries in posterior alpha-band oscillations during an auditory retroactive cueing task, we aimed at differentiating those mechanisms. Participants were cued to attend two out of three sounds in an upcoming sound array. Importantly, the resulting working memory representation contained one laterally and one centrally presented item. A centrally presented retro-cue then indicated the lateral, the central, or both items as further relevant for the task (comparing the cued item(s) to a memory probe). Time-frequency analysis revealed opposing patterns of alpha lateralization depending on target eccentricity: A contralateral decrease in alpha power in target lateral trials indicated the involvement of target prioritization. A contralateral increase in alpha power when the central item remained relevant (distractor lateral trials) suggested the de-prioritization of irrelevant information. No lateralization was observed when both items remained relevant, supporting the notion that auditory alpha lateralization is restricted to situations in which spatial information is task-relevant. Altogether, the data demonstrate that retroactive attentional deployment involves excitatory and inhibitory control mechanisms.

Real-time biofeedback integrated into neuromuscular training reduces high-risk knee biomechanics and increases functional brain connectivity: A preliminary longitudinal investigation.

Prospective evidence indicates that functional biomechanics and brain connectivity may predispose an athlete to an anterior cruciate ligament injury, revealing novel neural linkages for targeted neuromuscular training interventions. The purpose of this study was to determine the efficacy of a real-time biofeedback system for altering knee biomechanics and brain functional connectivity. Seventeen healthy, young, physically active female athletes completed 6 weeks of augmented neuromuscular training (aNMT) utilizing real-time, interactive visual biofeedback and 13 served as untrained controls. A drop vertical jump and resting state functional magnetic resonance imaging were separately completed at pre- and posttest time points to assess sensorimotor adaptation. The aNMT group had a significant reduction in peak knee abduction moment (pKAM) compared to controls (p = .03, d = 0.71). The aNMT group also exhibited a significant increase in functional connectivity between the right supplementary motor area and the left thalamus (p = .0473 after false discovery rate correction). Greater percent change in pKAM was also related to increased connectivity between the right cerebellum and right thalamus for the aNMT group (p = .0292 after false discovery rate correction, r2  = .62). No significant changes were observed for the controls (ps > .05). Our data provide preliminary evidence of potential neural mechanisms for aNMT-induced motor adaptations that reduce injury risk. Future research is warranted to understand the role of neuromuscular training alone and how each component of aNMT influences biomechanics and functional connectivity.

Neural responses to dynamic multimodal stimuli and pathology-specific impairments of social cognition in schizophrenia and depression.

BACKGROUND: Individuals with schizophrenia and people with depression both show abnormal behavioural and neural responses when perceiving and responding to emotional stimuli, but pathology-specific differences and commonalities remain mostly unclear. AIMS: To directly compare empathic responses to dynamic multimodal emotional stimuli in a group with schizophrenia and a group with depression, and to investigate their neural correlates using functional magnetic resonance imaging (fMRI). METHOD: The schizophrenia group (n = 20), the depression group (n = 24) and a control group (n = 24) were presented with portrait-shot video clips expressing emotion through three possible communication channels: facial expression, prosody and content. Participants rated their own and the actor's emotional state as an index of empathy. RESULTS: Although no group differences were found in empathy ratings, characteristic differences emerged in the fMRI activation patterns. The schizophrenia group demonstrated aberrant activation patterns during the neutral speech content condition in regions implicated in multimodal integration and formation of semantic constructs. Those in the depression group were most affected during conditions with trimodal emotional and trimodal neutral stimuli, in key regions of the mentalising network. CONCLUSIONS: Our findings reveal characteristic differences in patients with schizophrenia compared with those with depression in their cortical responses to dynamic affective stimuli. These differences indicate that impairments in responding to emotional stimuli may be caused by pathology-specific problems in social cognition.

The differential contribution of facial expressions, prosody, and speech content to empathy.

BACKGROUND: Facial expressions, prosody, and speech content constitute channels by which information is exchanged. Little is known about the simultaneous and differential contribution of these channels to empathy when they provide emotionality or neutrality. Especially neutralised speech content has gained little attention with regards to influencing the perception of other emotional cues. METHODS: Participants were presented with video clips of actors telling short-stories. One condition conveyed emotionality in all channels while the other conditions either provided neutral speech content, facial expression, or prosody, respectively. Participants judged the emotion and intensity presented, as well as their own emotional state and intensity. Skin conductance served as a physiological measure of emotional reactivity. RESULTS: Neutralising channels significantly reduced empathic responses. Electrodermal recordings confirmed these findings. The differential effect of the communication channels on empathy prerequisites was that target emotion recognition of the other decreased mostly when the face was neutral, whereas decreased emotional responses attributed to the target emotion were especially present in neutral speech. CONCLUSION: Multichannel integration supports conscious and autonomous measures of empathy and emotional reactivity. Emotional facial expressions influence emotion recognition, whereas speech content is important for responding with an adequate own emotional state, possibly reflecting contextual emotion-appraisal.

Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.

BACKGROUND: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy. METHODS: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes for each objective. Patients in this open-label trial were randomly assigned by a computer algorithm in a 2:3:3 ratio (tamoxifen:CAF-T:CAFT) and analysis was by intention to treat of eligible patients. Groups were compared by stratified log-rank tests, followed by Cox regression analyses adjusted for significant prognostic factors. This trial is registered with ClinicalTrials.gov, number NCT00929591. FINDINGS: Of 1558 randomised women, 1477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64-0.91; p=0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68-1.01; p=0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70-1.01; p=0.061) or overall survival (HR 0.90, 0.73-1.10; p=0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group. INTERPRETATION: Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive, node-positive breast cancer than is tamoxifen alone. However, it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes. FUNDING: National Cancer Institute (US National Institutes of Health).

Identification of mutations in Caenorhabditis elegans that cause resistance to high levels of dietary zinc and analysis using a genomewide map of single nucleotide polymorphisms scored by pyrosequencing.

Zinc plays many critical roles in biological systems: zinc bound to proteins has structural and catalytic functions, and zinc is proposed to act as a signaling molecule. Because zinc deficiency and excess result in toxicity, animals have evolved sophisticated mechanisms for zinc metabolism and homeostasis. However, these mechanisms remain poorly defined. To identify genes involved in zinc metabolism, we conducted a forward genetic screen for chemically induced mutations that cause Caenorhabditis elegans to be resistant to high levels of dietary zinc. Nineteen mutations that confer significant resistance to supplemental dietary zinc were identified. To determine the map positions of these mutations, we developed a genomewide map of single nucleotide polymorphisms (SNPs) that can be scored by the high-throughput method of DNA pyrosequencing. This map was used to determine the approximate chromosomal position of each mutation, and the accuracy of this approach was verified by conducting three-factor mapping experiments with mutations that cause visible phenotypes. This is a generally applicable mapping approach that can be used to position a wide variety of C. elegans mutations. The mapping experiments demonstrate that the 19 mutations identify at least three genes that, when mutated, confer resistance to toxicity caused by supplemental dietary zinc. These genes are likely to be involved in zinc metabolism, and the analysis of these genes will provide insights into mechanisms of excess zinc toxicity.

The clinical relevance of microbiologic testing. Part 2: a comparative analysis of microbiologic samples secured simultaneously from the same sites and cultured in the same laboratory.

A field study using four different private periodontal practices and two independent laboratories was conducted to compare two microbiologic cultures sampled simultaneously from the same sites in 20 individual patients. Both paired samples were submitted separately to one of the two independent laboratories for bacterial identification and antibiotic sensitivity testing. The results from the two samples were quite variable. In only two instances did both specimens reveal the presence of identical bacterial species, but these specimens differed in both threshold levels and antibiotic sensitivity. When only bacteria above threshold levels were compared, total agreement was found in 11 of 20 cases. When examining antibiotic sensitivity, using 100% kill as the ideal, agreement between the two specimens was inconsistent The use or nonuse of tetracycline was in agreement 85% of the time, amoxicillin 75% of the time, metronidazole 70% of the time, and amoxicillin-metronidazole in combination 85% of the time. The two specimens agreed on the empirical use of amoxicillin 45% of the time, tetracycline 60% of the time, and metronidazole 60% of the time. The empirical use of amoxicillin-metronidazole in combination yielded 80% agreement when the results of both specimens were combined. The empirical use of amoxicillin-metronidazole combination therapy may be more clinically sound and cost effective than culturing and antibiotic selection based on the culture from any single microbiologic testing laboratory. This supports the data from a previous study that examined specimens secured simultaneously from the same site and submitted to two different testing laboratories. The failure of microbial testing to achieve a higher level of consistency between samples leaves the clinical efficacy of microbial testing in question.