Towards Optimal Testing of Auditory Memory : Methodological development of recording of the mismatch negativity (MMN) of the auditory event-related potential (ERP)

The overlapping sound pressure waves that enter our brain via the ears and auditory nerves must be organized into a coherent percept. Modelling the regularities of the auditory environment and detecting unexpected changes in these regularities, even in the absence of attention, is a necessary prerequisite for orientating towards significant information as well as speech perception and communication, for instance. The processing of auditory information, in particular the detection of changes in the regularities of the auditory input, gives rise to neural activity in the brain that is seen as a mismatch negativity (MMN) response of the event-related potential (ERP) recorded by electroencephalography (EEG). --- As the recording of MMN requires neither a subject s behavioural response nor attention towards the sounds, it can be done even with subjects with problems in communicating or difficulties in performing a discrimination task, for example, from aphasic and comatose patients, newborns, and even fetuses. Thus with MMN one can follow the evolution of central auditory processing from the very early, often critical stages of development, and also in subjects who cannot be examined with the more traditional behavioural measures of auditory discrimination. Indeed, recent studies show that central auditory processing, as indicated by MMN, is affected in different clinical populations, such as schizophrenics, as well as during normal aging and abnormal childhood development. Moreover, the processing of auditory information can be selectively impaired for certain auditory attributes (e.g., sound duration, frequency) and can also depend on the context of the sound changes (e.g., speech or non-speech). Although its advantages over behavioral measures are undeniable, a major obstacle to the larger-scale routine use of the MMN method, especially in clinical settings, is the relatively long duration of its measurement. Typically, approximately 15 minutes of recording time is needed for measuring the MMN for a single auditory attribute. Recording a complete central auditory processing profile consisting of several auditory attributes would thus require from one hour to several hours. In this research, I have contributed to the development of new fast multi-attribute MMN recording paradigms in which several types and magnitudes of sound changes are presented in both speech and non-speech contexts in order to obtain a comprehensive profile of auditory sensory memory and discrimination accuracy in a short measurement time (altogether approximately 15 min for 5 auditory attributes). The speed of the paradigms makes them highly attractive for clinical research, their reliability brings fidelity to longitudinal studies, and the language context is especially suitable for studies on language impairments such as dyslexia and aphasia. In addition I have presented an even more ecological paradigm, and more importantly, an interesting result in view of the theory of MMN where the MMN responses are recorded entirely without a repetitive standard tone. All in all, these paradigms contribute to the development of the theory of auditory perception, and increase the feasibility of MMN recordings in both basic and clinical research. Moreover, they have already proven useful in studying for instance dyslexia, Asperger syndrome and schizophrenia.Tarkoituksenmukainen ääniympäristössä toimiminen, kuten ääniympäristön merkityksellisiin tapahtumiin suuntautuminen ja kielellinen kommunikointi edellyttävät ääniympäristön säännömukaisuuksien, ja näistä poikkeavien tapahtumien tarkkaavuudesta riippumatonta mallintamista ja jäsentämistä yhtenäiseksi havaintokokonaisuudeksi. Tällaisen esitietoisen kuuloinformaation käsittelyn, erityisesti ääniympäristöstä poikkeavien äänien havaitsemisesta syntyvä hermosolujen aktivoituminen näkyy aivosähkökäyrässä tapahtumasidonnaisena MMN-jännitevasteena. --- Koska MMN:n rekisteröiminen ei edellytä tutkittavalta tehtävän tekemistä tai ärsykkeiden aktiivista kuuntelemista, sen avulla voidaan tutkia sensorisen kuulomuistin toimintaa jo vauvaiästä vanhuuteen saakka. Perustutkimuksen lisäksi MMN:ää voidaan hyödyntää erilaisten aivoperäisten ja aivoihin vaikuttavien sairauksien ja tilojen, kuten lukihäiriön, ikääntymisen ja skitsofrenian tutkimuksessa. Viimeaikaiset tutkimukset osoittavatkin, että kuuloinformaation prosessointi MMN:llä tutkittuna on poikkeavaa erilaisissa aivosairauksissa kuten skitsofreniassa, mutta muuttuu myös kehityksen ja normaalin ikääntymisen myötä. Edelleen on osoitettu, että nämä kuuloinformaation prosessoinnin muutokset voivat ilmetä valikoivasti joillekin äänen piirteille (esim. äänen kesto tai taajuus) sekä vain joissakin yhteyksissä (esim. vain puheäänissä). Vaikka MMN-tutkimuksella onkin huomattavia etuja verrattuna behavioraalisiin menetelmiin, sen yleistymistä laajempaan käyttöön, erityisesti kliiniseen tutkimukseen ja diagnostiikkaan, jarruttaa MMN-rekisteröinnin suhteellinen hitaus. Tavallisesti MMN-rekisteröinti yhdelle äänen piirteelle vaatii n. 15 minuuttia, joten useamman äänen piirteen erottelun profiilin rekisteröiminen vie helposti tunnista useaankin tuntiin. Tässä väitöskirjatutkimuksessa tavoitteena oli kehittää MMN-rekisteröinnissä käytettävää koeasetelmaa siten, että rekisteröinti voitaisiin tehdä aiempaa nopeammin, mutta yhtä luotettavasti. Väitöskirjatutkimuksessa kehitettiin koeasetelmia, joilla voidaan rekisteröidä lyhyessä ajassa (noin 15 minuuttia viidelle eri äänen piirteelle) useiden äänten piirteiden ja erikokoisten äänimuutosten prosessoinnin profiilit sekä puheäänille että ei-puheäänille. Koska näillä koeasetelmilla saadaan tietoa kuuloinformaation prosessoinnista huomattavasti aikaisempaa lyhyemmässä ajassa, ne parantavat MMN:n käytettävyyttä erityisesti kliinisissä tutkimuksissa. Edelleen, lyhyt rekisteröintiaika mahdollistaa entistä kattavamman ja monipuolisemman kuvan muodostamisen tutkittavien erottelukyystä eri äänen piirteiden välillä. Korkea reliabiliteetti puolestaan tuo luotettavuutta erityisesti pitkittäistutkimuksiin ja puhekonteksti soveltuu erityisesti kielen ja sen häiriöiden kuten dysfasian ja afasian tutkimukseen. Kehitimme myös vielä näitäkin taloudellisemman koeasetelman, jossa MMN vaste rekisteröitiin uudella tavalla, ilman toistuvaa ääntä ja tämän osatutkimuksen tulos on merkittävä myös MMN:n ja kuuloinformaation prosessoinnin teorian kannalta. Kaiken kaikkiaan nämä väitöskirjatyössä kehitetyt koeasetelmat tuovat uutta tietoa kuuloinformaation käsittelystä, ja parantavat huomattavasti MMN-menetelmän käytettävyyttä sekä perus- että kliinisessä tutkimuksessa. On myös huomionarvoista, että näiden koeasetelmien on jo osoitettu olevan hyödyllisiä mm. lukihäiriön, Aspergerin syndrooman ja skitsofrenian tutkimuksessa

Quality assurance plan for the ReCreate project

This document is the Quality Assurance Plan for the ReCreate project. The document describes the procedures to be used throughout the project to coordinate the timely delivery of high-quality deliverables, other publications, and project outcomes. This plan will act as a guide for the project leadership to ensure that quality is assured in due course before deliverables and/or other publications are submitted. In addition, the plan will help all project partners to understand their responsibilities in terms of the quality of project processes, deliverables and outcomes. The plan defines the steps of quality assurance to make it easy for the responsible partners to identify the tasks that are important for ensuring high-quality outputs and sufficient communications between relevant partners. It helps to monitor the project’s progress and to foresee difficulties that may result in delays, and defines actions to be undertaken in the occurrence of such situations.publishedVersio

Project handbook for the ReCreate project

This document is the Project Handbook for the ReCreate project. The purpose of the handbook is to support the ReCreate partners in implementing the project activities. It should be understood as an internal guidebook and a reference for the project execution. The handbook contains pieces of key information from the Grant and Consortium Agreements in an easily understandable and accessible format. It is a dynamic document that will be updated as needed throughout the lifetime of the project.publishedVersio

Mapping symbols to sounds: electrophysiological correlates of the impaired reading process in dyslexia

Dyslexic and control first-grade school children were compared in a Symbol-to-Sound matching test based on a non-linguistic audiovisual training which is known to have a remediating effect on dyslexia. Visual symbol patterns had to be matched with predicted sound patterns. Sounds incongruent with the corresponding visual symbol (thus not matching the prediction) elicited the N2b and P3a event-related potential (ERP) components relative to congruent sounds in control children. Their ERPs resembled the ERP effects previously reported for healthy adults with this paradigm. In dyslexic children, N2b onset latency was delayed and its amplitude significantly reduced over left hemisphere whereas P3a was absent. Moreover, N2b amplitudes significantly correlated with the reading skills. ERPs to sound changes in a control condition were unaffected. In addition, correctly predicted sounds, that is, sounds that are congruent with the visual symbol, elicited an early induced auditory gamma band response (GBR) reflecting synchronization of brain activity in normal-reading children as previously observed in healthy adults. However, dyslexic children showed no GBR. This indicates that visual symbolic and auditory sensory information are not integrated into a unitary audiovisual object representation in them. Finally, incongruent sounds were followed by a later desynchronization of brain activity in the gamma band in both groups. This desynchronization was significantly larger in dyslexic children. Although both groups accomplished the task successfully remarkable group differences in brain responses suggest that normal-reading children and dyslexic children recruit (partly) different brain mechanisms when solving the task. We propose that abnormal ERPs and GBRs in dyslexic readers indicate a deficit resulting in a widespread impairment in processing and integrating auditory and visual information and contributing to the reading impairment in dyslexia

Long-term outcomes of biliary atresia patients surviving with their native livers

Publisher Copyright: © 2021 The Author(s)Portoenterostomy (PE) has remained as the generally accepted first line surgical treatment for biliary atresia (BA) for over 50 years. Currently, close to half of BA patients survive beyond 10 years with their native livers, and most of them reach adulthood without liver transplantation (LT). Despite normalization of serum bilirubin by PE, ductular reaction and portal fibrosis persist in the native liver. The chronic cholangiopathy progresses to cirrhosis, complications of portal hypertension, recurrent cholangitis or hepatobiliary tumors necessitating LT later in life. Other common related health problems include impaired bone health, neuromotor development and quality of life. Only few high-quality trials are available for evidence-based guidance of post-PE adjuvant medical therapy or management of the disease complications. Better understanding of the pathophysiological mechanisms connecting native liver injury to clinical outcomes is critical for development of accurate follow-up tools and novel therapies designed to improve native liver function and survival.Peer reviewe

Neural processing of changes in phonetic and emotional speech sounds and tones in preterm infants at term age

Objective: Auditory change-detection responses provide information on sound discrimination and memory skills in infants. We examined both the automatic change-detection process and the processing of emotional information content in speech in preterm infants in comparison to full-term infants at term age. Methods: Preterm (n = 21) and full-term infants' (n = 20) event-related potentials (ERP) were recorded at term age. A challenging multi-feature mismatch negativity (MMN) paradigm with phonetic deviants and rare emotional speech sounds (happy, sad, angry), and a simple one-deviant oddball paradigm with pure tones were used. Results: Positive mismatch responses (MMR) were found to the emotional sounds and some of the phonetic deviants in preterm and full-term infants in the multi-feature MMN paradigm. Additionally, late positive MMRs to the phonetic deviants were elicited in the preterm group. However, no group differences to speech-sound changes were discovered. In the oddball paradigm, preterm infants had positive MMRs to the deviant change in all latency windows. Responses to non-speech sounds were larger in preterm infants in the second latency window, as well as in the first latency window at the left hemisphere electrodes (F3, C3). Conclusions: No significant group-level differences were discovered in the neural processing of speech sounds between preterm and full-term infants at term age. Change-detection of non-speech sounds, however, may be enhanced in preterm infants at term age. Significance: Auditory processing of speech sounds in healthy preterm infants showed similarities to full-term infants at term age. Large individual variations within the groups may reflect some underlying differences that call for further studies.Peer reviewe

Shifting of attentional set is inadequate in severe burnout : Evidence from an event-related potential study

Individuals with prolonged occupational stress often report difficulties in concentration. Work tasks often require the ability to switch back and forth between different contexts. Here, we studied the association between job burnout and task switching by recording event-related potentials (ERPs) time-locked to stimulus onset during a task with simultaneous cue-target presentation and unpredictable switches in the task. Participants were currently working people with severe, mild, or no burnout symptoms. In all groups, task performance was substantially slower immediately after task switch than during task repetition. However, the error rates were higher in the severe burnout group than in the mild burnout and control groups. Electrophysiological data revealed an increased parietal P3 response for the switch trials relative to repetition trials. Notably, the response was smaller in amplitude in the severe burnout group than in the other groups. The results suggest that severe burnout is associated with inadequate processing when rapid shifting of attention between tasks is required resulting in less accurate performance. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Growth of children with biliary atresia living with native livers : impact of corticoid therapy after portoenterostomy

We addressed growth of biliary atresia (BA) patients living with native livers between ages 0-6 and effects of post-surgical corticosteroid treatment on growth. Growth charts of 28 BA patients born in Finland between 1987 and 2017 were retrospectively evaluated. Dosage and length of corticosteroid treatment and hydrocortisone substitution were reviewed. At birth, BA patients were shorter (median height -0.6 (interquartile range (IQR) -1.3 to -0.1) SDS, n=28, PPeer reviewe

Healthy full-term infants' brain responses to emotionally and linguistically relevant sounds using a multi-feature mismatch negativity (MMN) paradigm

We evaluated the feasibility of a multi-feature mismatch negativity (MMN) paradigm in studying auditory processing of healthy newborns. The aim was to examine the automatic change-detection and processing of semantic and emotional information in speech in newborns. Brain responses of 202 healthy newborns were recorded with a multi-feature paradigm including a Finnish bi-syllabic pseudo-word/ta-ta/as a standard stimulus, six linguistically relevant deviant stimuli and three emotionally relevant stimuli (happy, sad, angry). Clear responses to emotional sounds were found already at the early latency window 100-200 ms, whereas responses to linguistically relevant minor changes and emotional stimuli at the later latency window 300-500 ms did not reach significance. Moreover, significant interaction between gender and emotional stimuli was found in the early latency window. Further studies on using multi-feature paradigms with linguistic and emotional stimuli in newborns are needed, especially those containing of follow-ups, enabling the assessment of the predictive value of early variations between subjects.Peer reviewe

Serum FGF19 predicts outcomes of Kasai portoenterostomy in biliary atresia

BACKGROUND AND AIMS: Outcomes after Kasai portoenterostomy (KPE) for biliary atresia remain highly variable for unclear reasons. As reliable early biomarkers predicting KPE outcomes are lacking, we studied the prognostic value of FGF19. APPROACH AND RESULTS: Serum and liver specimens, obtained from biliary atresia patients (N=87) at KPE or age-matched cholestatic controls (N=26) were included. Serum concentration of FGF19 and bile acids, liver mRNA expression of FGF19, and key regulators of bile acid synthesis were related to KPE outcomes and liver histopathology. Immunohistochemistry and in situ hybridization were used for the localization of liver FGF19 expression. Serum levels (223 vs. 61 pg/mL, p<0.001) and liver mRNA expression of FGF19 were significantly increased in biliary atresia. Patients with unsuccessful KPE (419 vs. 145 pg/mL, p=0.047), and those subsequently underwent liver transplantation (410 vs. 99 pg/mL, p=0.007) had significantly increased serum, but not liver, FGF19, which localized mainly in hepatocytes. In Cox hazard modeling serum FGF19 <109 pg/mL predicted native liver survival (HR: 4.31, p<0.001) also among patients operated <60 days of age (HR: 8.77, p=0.004) or after successful KPE (HR: 6.76, p=0.01). Serum FGF19 correlated positively with increased serum primary bile acids (R=0.41, p=0.004) and ductular reaction (R=0.39, p=0.004). CONCLUSIONS: Increased serum FGF19 at KPE predicted inferior long-term native liver survival in biliary atresia and was associated with unsuccessful KPE, elevated serum primary bile acids, and ductular reaction