Transitional probabilities are prioritized over stimulus/pattern probabilities in auditory deviance detection: Memory basis for predictive sound processing

Representations encoding the probabilities of auditory events do not directly support predictive processing. In contrast, information about the probability with which a given sound follows another (transitional probability) allows predictions of upcoming sounds. We tested whether behavioral and cortical auditory deviance detection (the latter indexed by the mismatch negativity event-related potential) relies on probabilities of sound patterns or on transitional probabilities. We presented healthy adult volunteers with three types of rare tone-triplets among frequent standard triplets of High-Low-High (HLH) or LHL pitch structure: proximity deviant (HHH/LLL), reversal deviant (LHL/HLH), and first-tone deviant (LLH/HHL). If deviance detection was based on pattern probability, reversal and first-tone deviants should be detected with similar latency because both differ from the standard at the first pattern position. If deviance detection was based on transitional probabilities, then reversal deviants should be the most difficult to detect, because, unlike the other two deviants, they contain no low-probability pitch transitions. The data clearly showed that both behavioral and cortical auditory deviance detection utilizes transitional probabilities. Thus the memory traces underlying cortical deviance detection may provide a link between stimulus-probability based change/novelty detectors operating at lower levels of the auditory system and higher auditory cognitive functions that involve predictive processing

Interactions of the processing of letters and speech sounds as reflected by event-related brain potentials

The processing of audiovisual information is ubiquitous in our daily life. As such, understanding the cortical correlates of audiovisual processing and its interactions offers a promise of practical interventions in many real-life settings. Reading, as one example, relies on the formation of artificial audiovisual associations and requires adaptions from brain mechanisms in order to process and integrate these connections effortlessly. In dyslexia, reading problems are associated with a failure in forming those associations, and neural changes and improvements of reading skills in children with dyslexia were reported after interventions ameliorated those processes. The present thesis investigates the neural networks associated with speech sound processing and discrimination when accompanied by printed text. In all studies, a high-density EEG system was utilized, enabling the examination of spatio-temporal dynamics of audiovisual processing in adult fluent readers and in readers with dyslexia. In fluent adult readers, change-related responses to consonant and pitch changes were greater when presented with printed text than with scrambled images, suggesting that letters modulate speech sound discrimination at an early cortical processing stage. This integration was sensitive to precise temporal alignment between the sounds and printed text, as it broke down when a time delay between the sounds and print was introduced. In contrast to fluent readers, adult readers with dyslexia showed a general attenuated discrimination of speech sounds when presented with print. Their neural responses for speech sounds presented with print did not differ from those presented with scrambled images. Our results, therefore, suggest that audiovisual processing is generally impaired in dyslexia, and support the notion that letter representations are poorer in readers with dyslexia than fluent readers. In addition, audiovisual processing was delayed in readers with dyslexia, suggesting a deficit in concurrent processing of multiple sensory cues. The studies of this thesis also show that attention to one of the modalities is needed for the audiovisual integration to occur, and, moreover, that audiovisual attention boosts the integration. Furthermore, our results reveal that, in addition to attention, the phonological content of the task modulates letter-speech sound processing. The studies presented in the present thesis confirmed, with a more controlled methodology, that letters modulate speech sound discrimination at an early neural level. The present results illuminate the way these processes are impaired in dyslexia, and, further, that audiovisual attention is most beneficial for such an integration to occur. To conclude, the studies at hand have shed novel light on the basic and aberrant mechanisms of letter-speech sound processing, and can be used, for instance, in training programs to promote accurate mapping of letters and speech sounds, and, consequently, reading skills in individuals with dyslexia.Tiedon audiovisuaalinen käsittely liittyy jokapäiväiseen toimintaamme. Näkö- ja kuulotiedon aivomekanismien ymmärtämisen pohjalta voidaan muun muassa kehittää erilaisia interventioita. Esimerkiksi lukemisen edellytyksenä on, että aivot käsittelevät tehokkaasti äänteiden ja kirjainten välisiä audiovisuaalisia yhteyksiä. Lukihäiriöisillä lukivaikeuksien taustalla voi olla audiovisuaalisten yhteyksien muodostamisen ongelmia ja audiovisuaalisten interventioiden onkin osoitettu lapsilla tehostaneen sekä hermoston tiedonkäsittelyä että lukutaitoa. Tässä väitöskirjassa selvitetään puheäänteiden ja samaan aikaan esitetyn tekstin yhtäaikaisen tiedonkäsittelyn hermostollista perustaa. Tutkimuksissa käytetään monikanavaista elektroenkefalografiaa (EEG), joka mahdollistaa aivojen audiovisuaalisen tiedonkäsittelyn tutkimisen sekä sujuvasti lukevilla että lukihäiriöisillä henkilöillä. Väitöskirjan tulokset osoittavat, että sujuvasti lukevilla aikuisilla konsonantin ja äänenkorkeuden muutosten hermostollinen tiedonkäsittely voimistui kun ne esitettiin kirjoitetun tekstin yhteydessä verrattuna siihen, että ne esitettiin merkityksettömien symbolien yhteydessä. Tulos viittaa siihen, että kirjainten näkeminen muokkaa puheäänteiden hermostollista tiedonkäsittelyä jo hyvin varhaisessa tiedonkäsittelyn vaiheessa. Tutkimuksissa havaittu hermostollisen tiedonkäsittelyn voimistuminen edellytti kuitenkin, että puheäänet ja teksti esitettiin samanaikaisesti sillä hermostollinen tiedonkäsittely ei voimistunut kun puheäänen ja tekstin esittämisen välillä oli ajallinen viive. Sujuvasti lukeviin aikuisiin verrattuna lukihäiriöisillä samanaikaisesti esitettyjen puheäänten ja tekstin hermostollinen tiedonkäsittely oli vaimeampaa eikä siihen vaikuttanut se, että teksti oli korvattu merkityksettömillä symboleilla. Tulosten mukaan lukihäiriöisillä audiovisuaalinen tiedonkäsittely on kauttaaltaan heikentynyttä ja löydökset tukevat ajatusta siitä, että kirjainten hermostolliset edustukset ovat heikommin muodostuneita lukihäiriöisillä kuin sujuvasti lukevilla. Lisäksi lukihäiriöisillä audiovisuaalinen tiedonkäsittely oli ajallisesti viivästynyttä, mikä viittaa ongelmiin useiden aistimusten samanaikaisessa tiedonkäsittelyssä. Väitöskirjatutkimukset osoittivat myös tarkkaavaisuuden kohdistamisen ääniin tai tekstiin olevan tarpeellista, jotta tiedon integrointia aivoissa tapahtuisi. Tämä integraatioprosessi voimistui tarkkaavaisuuden kohdistuessa molempien aistien ärsykkeisiin. Tutkimusten mukaan tarkkaavuuden lisäksi myös tehtävässä käytetyn fonologisen aineksen sisällöllä oli vaikutusta kirjainten ja puheäänten audiovisuaaliseen tiedonkäsittelyyn. Kokonaisuudessaan väitöskirjatutkimukset osoittavat, että kirjaimet vaikuttavat puheäänteiden hermostolliseen tiedonkäsittelyyn jo hyvin varhaisessa tiedonkäsittelyn vaiheessa. Tulokset antavat uutta tietoa siitä, miksi nämä tiedonkäsittelyn prosessit ovat heikentyneet lukihäiriössä ja kuvaavat, kuinka audiovisuaalinen tarkkaavuus edesauttaa kirjainten ja puheäänten yhdistämistä aivoissa. Väitöskirjan tulokset laajentavat tietämystämme puheäänten ja kirjainten samanaikaisen tiedonkäsittelyn taustalla olevista aivomekanismeista ja tuloksia voidaan hyödyntää esimerkiksi interventiotutkimuksissa, joilla pyritään sujuvoittamaan lukemista lukihäiriöisillä tehostamalla kirjainten ja puheäänten yhdistämistä aivoissa

Predicting the Physiological Role of Circadian Metabolic Regulation in the Green Alga Chlamydomonas reinhardtii

Although the number of reconstructed metabolic networks is steadily growing, experimental data integration into these networks is still challenging. Based on elementary flux mode analysis, we combine sequence information with metabolic pathway analysis and include, as a novel aspect, circadian regulation. While minimizing the need of assumptions, we are able to predict changes in the metabolic state and can hypothesise on the physiological role of circadian control in nitrogen metabolism of the green alga Chlamydomonas reinhardtii

Attention effects on the processing of task-relevant and task-irrelevant speech sounds and letters

Peer reviewe

A marine chlamydomonas sp. emerging as an algal model

The freshwater microalga Chlamydomonas reinhardtii , which lives in wet soil, has served for decades as a model for numerous biological processes, and many tools have been introduced for this organism. Here, we have established a stable nuclear transformation for its marine counterpart, Chlamydomonas sp. SAG25.89, by fusing specific cis ‐acting elements from its Actin gene with the gene providing hygromycin resistance and using an elaborated electroporation protocol. Like C. reinhardtii , Chlamydomonas sp. has a high GC content, allowing reporter genes and selection markers to be applicable in both organisms. Chlamydomonas sp. grows purely photoautotrophically and requires ammonia as a nitrogen source because its nuclear genome lacks some of the genes required for nitrogen metabolism. Interestingly, it can grow well under both low and very high salinities (up to 50 g · L ‐1 ) rendering it as a model for osmotolerance. We further show that Chlamydomonas sp. grows well from 15 to 28°C, but halts its growth at 32°C. The genome of Chlamydomonas sp. contains some gene homologs the expression of which is regulated according to the ambient temperatures and/or confer thermal acclimation in C. reinhardtii . Thus, knowledge of temperature acclimation can now be compared to the marine species. Furthermore, Chlamydomonas sp. can serve as a model for studying marine microbial interactions and for comparing mechanisms in freshwater and marine environments. Chlamydomonas sp. was previously shown to be immobilized rapidly by a cyclic lipopeptide secreted from the antagonistic bacterium Pseudomonas protegens PF‐5, which deflagellates C. reinhardtii

From molecular manipulation of domesticated Chlamydomonas reinhardtii to survival in nature

In the mid-20th century, the unicellular and genetically tractable green alga Chlamydomonas reinhardtii was first developed as a model organism to elucidate fundamental cellular processes such as photosynthesis, light perception and the structure, function and biogenesis of cilia. Various studies of C. reinhardtii have profoundly advanced plant and cell biology, and have also impacted algal biotechnology and our understanding of human disease. However, the 'real' life of C. reinhardtii in the natural environment has largely been neglected. To extend our understanding of the biology of C. reinhardtii, it will be rewarding to explore its behavior in its natural habitats, learning more about its abundance and life cycle, its genetic and physiological diversity, and its biotic and abiotic interactions

A polyyne toxin produced by an antagonistic bacterium blinds and lyses a Chlamydomonad alga

Algae are key contributors to global carbon fixation and form the basis of many food webs. In nature, their growth is often supported or suppressed by microorganisms. The bacterium Pseudomonas protegens Pf-5 arrests the growth of the green unicellular alga Chlamydomonas reinhardtii, deflagellates the alga by the cyclic lipopeptide orfamide A, and alters its morphology [P. Aiyar et al., Nat. Commun. 8, 1756 (2017)]. Using a combination of Raman microspectroscopy, genome mining, and mutational analysis, we discovered a polyyne toxin, protegencin, which is secreted by P. protegens, penetrates the algal cells, and causes destruction of the carotenoids of their primitive visual system, the eyespot. Together with secreted orfamide A, protegencin thus prevents the phototactic behavior of C. reinhardtii. A mutant of P. protegens deficient in protegencin production does not affect growth or eyespot carotenoids of C. reinhardtii. Protegencin acts in a direct and destructive way by lysing and killing the algal cells. The toxic effect of protegencin is also observed in an eyeless mutant and with the colony-forming Chlorophyte alga Gonium pectorale. These data reveal a two-pronged molecular strategy involving a cyclic lipopeptide and a conjugated tetrayne used by bacteria to attack select Chlamydomonad algae. In conjunction with the bloom-forming activity of several chlorophytes and the presence of the protegencin gene cluster in over 50 different Pseudomonas genomes [A. J. Mullins et al., bioRxiv [Preprint] (2021). https://www.biorxiv.org/content/10.1101/2021.03.05.433886v1 (Accessed 17 April 2021)], these data are highly relevant to ecological interactions between Chlorophyte algae and Pseudomonadales bacteria

The bacterium Pseudomonas protegens antagonizes the microalga Chlamydomonas reinhardtii using a blend of toxins

The unicellular alga Chlamydomonas reinhardtii and the bacterium Pseudomonas protegens serve as a model to study the interactions between photosynthetic and heterotrophic microorganisms. P . protegens secretes the cyclic lipopeptide orfamide A that interferes with cytosolic Ca 2+ homeostasis in C . reinhardtii resulting in deflagellation of the algal cells. Here, we studied the roles of additional secondary metabolites secreted by P . protegens using individual compounds and co‐cultivation of algae with bacterial mutants. Rhizoxin S2, pyrrolnitrin, pyoluteorin, 2,4‐diacetylphloroglucinol (DAPG) and orfamide A all induce changes in cell morphology and inhibit the growth of C . reinhardtii . Rhizoxin S2 exerts the strongest growth inhibition, and its action depends on the spatial structure of the environment (agar versus liquid culture). Algal motility is unaffected by rhizoxin S2 and is most potently inhibited by orfamide A (IC 50 = 4.1 μM). Pyrrolnitrin and pyoluteorin both interfere with algal cytosolic Ca 2+ homeostasis and motility whereas high concentrations of DAPG immobilize C . reinhardtii without deflagellation or disturbance of Ca 2+ homeostasis. Co‐cultivation with a regulatory mutant of bacterial secondary metabolism (Δ gacA ) promotes algal growth under spatially structured conditions. Our results reveal how a single soil bacterium uses an arsenal of secreted antialgal compounds with complementary and partially overlapping activities

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella