Disentangling the effects of phonation and articulation: Hemispheric asymmetries in the auditory N1m response of the human brain

BACKGROUND: The cortical activity underlying the perception of vowel identity has typically been addressed by manipulating the first and second formant frequency (F1 & F2) of the speech stimuli. These two values, originating from articulation, are already sufficient for the phonetic characterization of vowel category. In the present study, we investigated how the spectral cues caused by articulation are reflected in cortical speech processing when combined with phonation, the other major part of speech production manifested as the fundamental frequency (F0) and its harmonic integer multiples. To study the combined effects of articulation and phonation we presented vowels with either high (/a/) or low (/u/) formant frequencies which were driven by three different types of excitation: a natural periodic pulseform reflecting the vibration of the vocal folds, an aperiodic noise excitation, or a tonal waveform. The auditory N1m response was recorded with whole-head magnetoencephalography (MEG) from ten human subjects in order to resolve whether brain events reflecting articulation and phonation are specific to the left or right hemisphere of the human brain. RESULTS: The N1m responses for the six stimulus types displayed a considerable dynamic range of 115–135 ms, and were elicited faster (~10 ms) by the high-formant /a/ than by the low-formant /u/, indicating an effect of articulation. While excitation type had no effect on the latency of the right-hemispheric N1m, the left-hemispheric N1m elicited by the tonally excited /a/ was some 10 ms earlier than that elicited by the periodic and the aperiodic excitation. The amplitude of the N1m in both hemispheres was systematically stronger to stimulation with natural periodic excitation. Also, stimulus type had a marked (up to 7 mm) effect on the source location of the N1m, with periodic excitation resulting in more anterior sources than aperiodic and tonal excitation. CONCLUSION: The auditory brain areas of the two hemispheres exhibit differential tuning to natural speech signals, observable already in the passive recording condition. The variations in the latency and strength of the auditory N1m response can be traced back to the spectral structure of the stimuli. More specifically, the combined effects of the harmonic comb structure originating from the natural voice excitation caused by the fluctuating vocal folds and the location of the formant frequencies originating from the vocal tract leads to asymmetric behaviour of the left and right hemisphere

A Population Rate Code of Auditory Space in the Human Cortex

BACKGROUND:Previous work on the human auditory cortex has revealed areas specialized in spatial processing but how the neurons in these areas represent the location of a sound source remains unknown. METHODOLOGY/PRINCIPAL FINDINGS:Here, we performed a magnetoencephalography (MEG) experiment with the aim of revealing the neural code of auditory space implemented by the human cortex. In a stimulus-specific adaptation paradigm, realistic spatial sound stimuli were presented in pairs of adaptor and probe locations. We found that the attenuation of the N1m response depended strongly on the spatial arrangement of the two sound sources. These location-specific effects showed that sounds originating from locations within the same hemifield activated the same neuronal population regardless of the spatial separation between the sound sources. In contrast, sounds originating from opposite hemifields activated separate groups of neurons. CONCLUSIONS/SIGNIFICANCE:These results are highly consistent with a rate code of spatial location formed by two opponent populations, one tuned to locations in the left and the other to those in the right. This indicates that the neuronal code of sound source location implemented by the human auditory cortex is similar to that previously found in other primates

Evidence for distinct human auditory cortex regions for sound location versus identity processing

Neurophysiological animal models suggest that anterior auditory cortex (AC) areas process sound-identity information, whereas posterior ACs specialize in sound location processing. In humans, inconsistent neuroimaging results and insufficient causal evidence have challenged the existence of such parallel AC organization. Here we transiently inhibit bilateral anterior or posterior AC areas using MRI-guided paired-pulse transcranial magnetic stimulation (TMS) while subjects listen to Reference/Probe sound pairs and perform either sound location or identity discrimination tasks. The targeting of TMS pulses, delivered 55–145 ms after Probes, is confirmed with individual-level cortical electric-field estimates. Our data show that TMS to posterior AC regions delays reaction times (RT) significantly more during sound location than identity discrimination, whereas TMS to anterior AC regions delays RTs significantly more during sound identity than location discrimination. This double dissociation provides direct causal support for parallel processing of sound identity features in anterior AC and sound location in posterior AC

Top-quality embryo transfer is associated with lower odds of ectopic pregnancy

Introduction The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. Material and Methods An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6-8 gestational weeks) after non-donor IVF/ICSI with fresh embryo transfer (n = 8952) or frozen-thawed embryo transfer (n = 6054). Treatments were performed during 2000-2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top-quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs. frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. Results Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs. 2.4%, p = 0.3). The ectopic pregnancy rate was lower in cycles with top-quality embryo transfer (1.9%) than of those where only non-top quality embryos were transferred (2.7%, p < 0.0001). Tubal factor infertility was diagnosed more often in ectopic pregnancy than in intrauterine pregnancies (21.2% vs. 11.0%, p < 0.0001). Logistic regression revealed lower odds for ectopic pregnancy after a top-quality embryo transfer than after transfer of a non-top quality embryo (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.56-0.92, p = 0.007). Transfer of two vs. one embryo (OR 1.35, 95% CI 1.05-1.70, p = 0.02) and tubal factor infertility (OR 2.21, 95% CI 1.68-2.91, p < 0.0001) significantly increased the risk of ectopic pregnancy. Conclusions Transfer of non-top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non-top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible.Peer reviewe

Total stimulation gonadotropin dose per oocyte retrieved and fresh embryo quality affect live birth rate after frozen-thawed embryo transfer

Koeputkihedelmöityshoidoissa (IVF) ja munasolujen mikroinjektiohoidoissa (ICSI) elävän lapsen syntymisen todennäköisyyteen vaikuttavia tekijöitä ovat muun muassa kerättyjen munasolujen lukumäärä, saatu gonadotropiinihormonin (FSH) annos sekä luotujen korkealaatuisten alkioiden määrä. Tämän tutkimuksen tarkoituksena oli selvittää, mitkä ominaisuudet alkion tuoresiirtovaiheessa vaikuttavat syntymän todennäköisyyteen jatkossa, jos naiselle tehdään myöhemmin hedelmöityshoidossa pakastetun alkion siirto. Tutkimusaineistona oli yhteinen Suomen lapsettomuusklinikoista kerätty tietokanta, joka sisälsi tiedot yhteensä 9465 pakastusalkionsiirto-tyyppisestä hedelmöityshoidosta vuosilta 2000-2017. Tuorealkionsiirtoja tutkittiin verraten näitä samojen naisten myöhempiin pakastealkionsiirtoihin. Luteaalisen kierron hormonaalista tukea sai naisista 42.9 %, hormonaalisesti indusoitu kuukautiskierto ja ovulaatio oli 40.7 % naisista, ja 16.1 % naisista kuukautiskierto oli täysin spontaani. FSH-annosta/munasolu käytettiin munasarjojen vasteen arviointiin. Tutkimuksessa selvisi, että vertailussa matalin FSH/munasolu -annossuhde <200 IU/munasolu sai aikaan suurimman todennäköisyyden elävän lapsen syntymälle pakastealkionsiirron jälkeen. Korkeampi annossuhde 300-399 IU/munasolu sen sijaan laski merkittävästi tätä todennäköisyyttä. Potilaan hormonaalisesti indusoitu ovulaatiokierto niin ikään assosioitui matalampaan syntymän todennäköisyyteen kuin kierto, jossa oli annettu hormonaalista tukea vain luteaalivaiheessa. Mikäli ainakin yksi korkealaatuinen alkio oli saatavilla hoitojen alussa, oli syntymän todennäköisyys suurempi läpi koko prosessin. Naisen yli 35 vuoden ikä laski syntymän todennäköisyyttä. Hedelmöityshoidoissa FSH/munasolu-annossuhde kuvastaa mahdollisesti munasarjojen toimintaa ja munasolujen laatua. Annossuhde tulisi pyrkiä pitämään mahdollisimman alhaisena, jotta vältytään korkeampiin annoksiin liittyvältä syntymän todennäköisyyden laskulta

Prevention of gestational diabetes with a prepregnancy lifestyle intervention - findings from a randomized controlled trial

Purpose: Lifestyle intervention studies performed during pregnancy have shown inconsistent results in relation to prevention of gestational diabetes mellitus (GDM). Therefore, the aim of this study was to assess the effect of an intervention initiated already before pregnancy in prevention of GDM in high-risk women. Patients and methods: A randomized controlled trial was conducted in four Finnish maternity hospitals between the years 2008 and 2014. Altogether 228 high-risk women planning pregnancy were randomized to an intervention (n=116) or a control group (n=112). The risk factors were body mass index >= 30 kg/m(2) (n=46), prior GDM (n=120), or both (n=62), without manifest diabetes at study inclusion. Trained study nurses provided individualized lifestyle counseling every 3 months in addition to a group session with a dietician. The control group received standard antenatal care. GDM was defined as one or more pathological glucose values in a 75 g 2-hour oral glucose tolerance test, performed between 12 and 16 weeks of gestation and if normal repeated between 24 and 28 weeks of gestation. Results: Within 12 months, 67% of the women (n=72) in the intervention group and 63% of the women (n=71) in the control group (p=0.84) became pregnant. The cumulative incidence of GDM among the women available for the final analyses was 60% (n=39/65) in the intervention group and 54% (n=34/63) in the control group (p=0.49). GDM was diagnosed already before 20 weeks of gestation in 60% (n=44/73) of the cases. Conclusion: The preconceptional lifestyle intervention applied in the present study did not reduce the incidence of GDM.Peer reviewe

Top-quality embryo transfer is associated with lower odds of ectopic pregnancy

Introduction The incidence of ectopic pregnancy is up to four times higher after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) than in spontaneous pregnancies, and the risk of ectopic pregnancy is increased by tubal factor infertility and the transfer of multiple embryos. However, the effect of embryo quality on the probability of ectopic pregnancy has not been investigated until now and it is not clear whether ovarian stimulation parameters affect the incidence of ectopic pregnancy. Material and Methods An historical cohort study of 15 006 clinical pregnancies (diagnosed by ultrasound at 6-8 gestational weeks) after non-donor IVF/ICSI with fresh embryo transfer (n = 8952) or frozen-thawed embryo transfer (n = 6054). Treatments were performed during 2000-2017 in Finland. A total of 9207 (61.4%) single and 5799 (38.6%) double embryo transfers of no more than one top-quality embryo were evaluated. We analyzed the effects of multiple factors on ectopic pregnancy by logistic regression, including type of cycle (fresh vs. frozen embryo transfer), female age, number and quality of embryos transferred, tubal factor infertility and factors of ovarian response to gonadotropin stimulation. Results Ectopic pregnancy was observed in 2.3% of cycles. There was no significant difference in ectopic pregnancy rate after fresh embryo transfer and frozen embryo transfer (2.2% vs. 2.4%, p = 0.3). The ectopic pregnancy rate was lower in cycles with top-quality embryo transfer (1.9%) than of those where only non-top quality embryos were transferred (2.7%, p Conclusions Transfer of non-top quality embryos is associated with a higher rate of ectopic pregnancy. This is particularly important to keep in mind in treatments with only non-top embryos available even in the absence of tubal factor infertility. To minimize the risk of ectopic pregnancy, the number of embryos transferred should be as low as possible.</p

Body size modifies the relationship between maternal serum 25-hydroxyvitamin D concentrations and gestational diabetes in high-risk women

Obesity increases the risk of low 25-hydroxyvitamin D (25(OH) D) concentrations and gestational diabetes (GDM). We explored whether the association between GDM and change in 25(OH) D concentrations measured in the first (7-18 wk) and second (20-27 wk) trimesters of pregnancy is dependent on maternal BMI. The study was a prospective study of 219 women with BMI of >= 30 kg/m2, a history of GDM, or both. The participants were stratified by first-trimester BMI: BMI of = 35 kg/m(2). In the BMI group >= 35 kg/m(2), those who did not develop GDM during the follow-up showed higher increase in serum 25(OH) D concentrations compared with women who developed GDM (43.2 vs. 11.5%; P <0.001). No associations between 25(OH) D concentrations and GDM were observed in other BMI groups. These findings give an important aspect of the role of maternal body size in the association between vitamin D and GDM in high-risk women.Peer reviewe

Sensitivity of the human auditory cortex to acoustic degradation of speech and non-speech sounds

The perception of speech is usually an effortless and reliable process even in highly adverse listening conditions. In addition to external sound sources, the intelligibility of speech can be reduced by degradation of the structure of speech signal itself, for example by digital compression of sound. This kind of distortion may be even more detrimental to speech intelligibility than external distortion, given that the auditory system will not be able to utilize sound source-specific acoustic features, such as spatial location, to separate the distortion from the speech signal. The perceptual consequences of acoustic distortions on speech intelligibility have been extensively studied. However, the cortical mechanisms of speech perception in adverse listening conditions are not well known at present, particularly in situations where the speech signal itself is distorted. The aim of this thesis was to investigate the cortical mechanisms underlying speech perception in conditions where speech is less intelligible due to external distortion or as a result of digital compression. In the studies of this thesis, the intelligibility of speech was varied either by digital compression or addition of stochastic noise. Cortical activity related to the speech stimuli was measured using magnetoencephalography (MEG). The results indicated that degradation of speech sounds by digital compression enhanced the evoked responses originating from the auditory cortex, whereas addition of stochastic noise did not modulate the cortical responses. Furthermore, it was shown that if the distortion was presented continuously in the background, the transient activity of auditory cortex was delayed. On the perceptual level, digital compression reduced the comprehensibility of speech more than additive stochastic noise. In addition, it was also demonstrated that prior knowledge of speech content enhanced the intelligibility of distorted speech substantially, and this perceptual change was associated with an increase in cortical activity within several regions adjacent to auditory cortex. In conclusion, the results of this thesis show that the auditory cortex is very sensitive to the acoustic features of the distortion, while at later processing stages, several cortical areas reflect the intelligibility of speech. These findings suggest that the auditory system rapidly adapts to the variability of the auditory environment, and can efficiently utilize previous knowledge of speech content in deciphering acoustically degraded speech signals.Puheen havaitseminen on useimmiten vaivatonta ja luotettavaa myös erittäin huonoissa kuunteluolosuhteissa. Puheen ymmärrettävyys voi kuitenkin heikentyä ympäristön häiriölähteiden lisäksi myös silloin, kun puhesignaalin rakennetta muutetaan esimerkiksi pakkaamalla digitaalista ääntä. Tällainen häiriö voi heikentää ymmärrettävyyttä jopa ulkoisia häiriöitä voimakkaammin, koska kuulojärjestelmä ei pysty hyödyntämään äänilähteen ominaisuuksia, kuten äänen tulosuuntaa, häiriön erottelemisessa puheesta. Akustisten häiriöiden vaikutuksia puheen havaitsemiseen on tutkttu laajalti, mutta havaitsemiseen liittyvät aivomekanismit tunnetaan edelleen melko puutteelisesti etenkin tilanteissa, joissa itse puhesignaali on laadultaan heikentynyt. Tämän väitöskirjan tavoitteena oli tutkia puheen havaitsemisen aivomekanismeja tilanteissa, joissa puhesignaali on vaikeammin ymmärrettävissä joko ulkoisen äänilähteen tai digitaalisen pakkauksen vuoksi. Väitöskirjan neljässä osatutkimuksessa lyhyiden puheäänien ja jatkuvan puheen ymmärrettävyyttä muokattiin joko digitaalisen pakkauksen kautta tai lisäämällä puhesignaaliin satunnaiskohinaa. Puheärsykkeisiin liittyvää aivotoimintaa tutkittiin magnetoenkefalografia-mittauksilla. Tutkimuksissa havaittiin, että kuuloaivokuorella syntyneet herätevasteet voimistuivat, kun puheääntä pakattiin digitaalisesti. Sen sijaan puheääniin lisätty satunnaiskohina ei vaikuttanut herätevasteisiin. Edelleen, mikäli puheäänien taustalla esitettiin jatkuvaa häiriötä, kuuloaivokuoren aktivoituminen viivästyi häiriön intensiteetin kasvaessa. Kuuntelukokeissa havaittiin, että digitaalinen pakkaus heikentää puheäänien ymmärrettävyyttä voimakkaammin kuin satunnaiskohina. Lisäksi osoitettiin, että aiempi tieto puheen sisällöstä paransi merkittävästi häiriöisen puheen ymmärrettävyyttä, mikä heijastui aivotoimintaan kuuloaivokuoren viereisillä aivoalueilla siten, että ymmärrettävä puhe aiheutti suuremman aktivaation kuin heikosti ymmärrettävä puhe. Väitöskirjan tulokset osoittavat, että kuuloaivokuori on erittäin herkkä puheäänien akustisille häiriöille, ja myöhemmissä prosessoinnin vaiheissa useat kuuloaivokuoren viereiset aivoalueet heijastavat puheen ymmärrettävyyttä. Tulosten mukaan voi olettaa, että kuulojärjestelmä mukautuu nopeasti ääniympäristön vaihteluihin muun muassa hyödyntämällä aiempaa tietoa puheen sisällöstä tulkitessaan häiriöistä puhesignaalia