Dataset size considerations for robust acoustic and phonetic speech encoding models in EEG

In many experiments that investigate auditory and speech processing in the brain using electroencephalography (EEG), the experimental paradigm is often lengthy and tedious. Typically, the experimenter errs on the side of including more data, more trials, and therefore conducting a longer task to ensure that the data are robust and effects are measurable. Recent studies used naturalistic stimuli to investigate the brain's response to individual or a combination of multiple speech features using system identification techniques, such as multivariate temporal receptive field (mTRF) analyses. The neural data collected from such experiments must be divided into a training set and a test set to fit and validate the mTRF weights. While a good strategy is clearly to collect as much data as is feasible, it is unclear how much data are needed to achieve stable results. Furthermore, it is unclear whether the specific stimulus used for mTRF fitting and the choice of feature representation affects how much data would be required for robust and generalizable results. Here, we used previously collected EEG data from our lab using sentence stimuli and movie stimuli as well as EEG data from an open-source dataset using audiobook stimuli to better understand how much data needs to be collected for naturalistic speech experiments measuring acoustic and phonetic tuning. We found that the EEG receptive field structure tested here stabilizes after collecting a training dataset of approximately 200 s of TIMIT sentences, around 600 s of movie trailers training set data, and approximately 460 s of audiobook training set data. Thus, we provide suggestions on the minimum amount of data that would be necessary for fitting mTRFs from naturalistic listening data. Our findings are motivated by highly practical concerns when working with children, patient populations, or others who may not tolerate long study sessions. These findings will aid future researchers who wish to study naturalistic speech processing in healthy and clinical populations while minimizing participant fatigue and retaining signal quality

Seismic Expression of Pleistocene Paleoceanographic Changes in the California Borderland from Digitally Acquired 3.5 Khz Subbottom Profiles and Ocean Drilling Program Leg 167 Drilling

We correlate processed 3.5 kHz seismic profiles with physical properties of cores collected during ODP Leg 167 from the Tanner, East Cortes, and San Nicolas Basins through much of the Pleistocene succession. Results indicate that seismic horizons in the unconsolidated Pleistocene sediments (top 50 m) are mainly controlled by density contrasts. Removing of the compaction trend from the density reveals a very interesting relationship between density and composition - the density closely and inversely correlates with organic carbon indicating that large-scale variations in organic carbon are responsible for seismic reflections through their influence on density. This is a significant discovery since there apparently is no other paleoceanographic setting that we know of where such a close linkage between acoustic properties and organic carbon has been established. The variations in organic carbon are mainly marine in origin and derive from variations in primary productivity associated with upwelling and the preservation regime related to oxygenation of water. Pleistocene reflections on 3.5 kHz profiles in the Borderland province thus record regional cyclical fluctuations in the paleoclimatic signals. The close resemblance in the density profiles at the three different basins indicates that the sedimentary regime was similar in those basins through the Pleistocene. These common density patterns produce regional seismic horizons that correlate well among the basins. It is likely these correlated and dated horizons could be extrapolated to other Borderland basins (e.g., San Clemente), where they can potentially be used as time markers for neotectonic studies in the region

iEEG-BIDS, extending the Brain Imaging Data Structure specification to human intracranial electrophysiology

The Brain Imaging Data Structure (BIDS) is a community-driven specification for organizing neuroscience data and metadata with the aim to make datasets more transparent, reusable, and reproducible. Intracranial electroencephalography (iEEG) data offer a unique combination of high spatial and temporal resolution measurements of the living human brain. To improve internal (re)use and external sharing of these unique data, we present a specification for storing and sharing iEEG data: iEEG-BIDS

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

Spontaneous Neural Activity in the Superior Temporal Gyrus Recapitulates Tuning for Speech Features

Background: Numerous studies have demonstrated that individuals exhibit structured neural activity in many brain regions during rest that is also observed during different tasks, however it is still not clear whether and how resting state activity patterns may relate to underlying tuning for specific stimuli. In the posterior superior temporal gyrus (STG), distinct neural activity patterns are observed during the perception of specific linguistic speech features. We hypothesized that spontaneous resting-state neural dynamics of the STG would be structured to reflect its role in speech perception, exhibiting an organization along speech features as seen during speech perception.Methods: Human cortical local field potentials were recorded from the superior temporal gyrus (STG) in 8 patients undergoing surgical treatment of epilepsy. Signals were recorded during speech perception and rest. Patterns of neural activity (high gamma power: 70–150 Hz) during rest, extracted with spatiotemporal principal component analysis, were compared to spatiotemporal neural responses to speech features during perception. Hierarchical clustering was applied to look for patterns in rest that corresponded to speech feature tuning.Results: Significant correlations were found between neural responses to speech features (sentence onsets, consonants, and vowels) and the spontaneous neural activity in the STG. Across subjects, these correlations clustered into five groups, demonstrating tuning for speech features—most robustly for acoustic onsets. These correlations were not seen in other brain areas, or during motor and spectrally-rotated speech control tasks.Conclusions: In this study, we present evidence that the RS structure of STG activity robustly recapitulates its stimulus-evoked response to acoustic onsets. Further, secondary patterns in RS activity appear to correlate with stimulus-evoked responses to speech features. The role of these spontaneous spatiotemporal activity patterns remains to be elucidated

Modulation and Manipulation of Sound Representation in the Auditory Cortex

The brain contains neurons of many different types interacting in complex functional circuits. To process sensory information these cells work in concert to form representations of the external world. In the auditory cortex, this involves integrating information from different cell types across an orderly anatomical structure of layers and columns. Representations can be observed at the level of single cells, cortical microcircuits, and large-scale sensory maps. The relationship between single cell properties and circuits within the auditory cortex, however, is still poorly understood. Furthermore, the structure-function relationships uncovered by neuroscientific study may crucially depend on the stimuli used to probe the system. This thesis brings together work from each of these different levels to describe how sounds are represented in the cortex, how this representation changes with experience, and how different cells contribute to cortical representation. First, I describe how the statistics of sound stimuli influence response properties in the mouse primary auditory cortex by comparing responses to pure tones and natural sounds (ultrasonic vocalizations). I also compare these responses to a temporally reversed vocalization to determine whether a sound with similar spectrotemporal content but no ethological relevance is represented similarly. When comparing pure tones and vocalizations, I find that the temporal response properties are similar, but that spectral response properties (e.g. frequency selectivity) often differ substantially. In particular, there are multiple sites that responded to vocalizations with frequency content outside their classical tone-derived receptive field, suggesting some specificity for behaviorally relevant sounds. When comparing forward and backward vocalizations, temporal responses are similar, but frequency bandwidth and characteristic frequency differs significantly across the population. Thus, the behaviorally relevant sound appears to be represented differently from non-behaviorally relevant synthetic and naturalistic sounds.The response properties of auditory neurons are not fixed, but rather depend on experience. In the next study, I examine how exposure to pulsed noise during different sensitive windows of the auditory critical period affects single site properties as well as circuit-level dynamics. On the single site level, I find that early exposure to pulsed noise increases receptive field thresholds and decreases frequency selectivity, while late noise exposure increases frequency bandwidths as well as spontaneous and evoked firing rates. To describe changes in functional microcircuits, I use the Ising model, which describes pairwise interactions between simultaneously recorded sites in the auditory cortex as well as interactions between sites and the stimuli that modulate them. I find that early noise exposure decreases stimulus drive, whereas late noise exposure does not change the strength of sound inputs but rather decreases the spread of functional connections from the deep to the superficial layers across sites with different frequency selectivity.Finally, I use a combination of optogenetic tools and computational methods to describe how the activity of a specific class of inhibitory neurons affects network connectivity in the auditory cortex. I examine the contribution of parvalbumin-positive (PV+) inhibitory interneurons, which make up around half of the inhibitory neurons in the cortex. These neurons are known to be involved in the generation of gamma oscillations, and their maturation corresponds with the end of the auditory critical period for plasticity. Using Ising models in tandem with linear-nonlinear vector autoregressive models, I show that stimulating PV+ neurons increases feedforward information flow through cortical circuits without changing lateral interactions within the same layers