Phonological neighbors cooperate during spoken-sentence processing: Evidence from a nonword detection task.

We used a novel nonword detection task to examine the lexical competition principle postulated in most models of spoken word recognition. To do so, in Experiment 1 we presented sequences of spoken words with half of the sequences containing a nonword, and the target nonword (i.e., press a response key whenever you detect a nonword in the sequence) could either be phonologically related (a phonological neighbor) or unrelated to the immediately preceding word. We reasoned that the reactivation of a phonological neighbor during target nonword processing should delay the moment at which a nonword decision can be made. Contrary to our hypothesis, participants were faster at detecting nonwords when they were preceded by a phonological neighbor compared with an unrelated word. In Experiment 2, an inhibitory effect of phonological relatedness on nonword decisions was observed in a classic priming situation using the same set of related and unrelated word-nonword pairs. We discuss the implications of these findings in regard to the main models of spoken word recognition, and conclude that our specific experimental set-up with phonological neighbors embedded in spoken sentences is more sensitive to cooperative interactions between co-activated sublexical representations than lexical competition between co-activated lexical representations, with the latter being modulated by whether or not the words compete for the same slot in time.

On the perception of stress position by French listeners: An EEG investigation.

In this EEG study, we examined the ability of French listeners to perceive and use the position of stress in a discrimination task. Event-Related-Potentials (ERPs) were recorded while participants performed a same-different task. Different stimuli diverged either in one phoneme (e.g., /ʒy'ʁi/-/ʒy'ʁɔ̃/) or in stress position (e.g., /ʒy'ʁi/-/'ʒyʁi/). Although participants reached 93% of correct responses, ERP results indicated that a change in stress position was not detected while a change in one phoneme elicited a MisMatchNegativity (MMN) response. It results that in the early moments of speech processing, stimuli that are phonemically identical but that differ in stress position are perceived as being strictly similar. We concluded that the good performance observed in behavioral responses on stress position contrasts are due to attentional/decisional processes linked to discrimination tasks, and not to automatic and unconscious processes involved in stress position processing.

Unlocking Therapeutic Synergy: Tailoring Drugs for Comorbidities such as Depression and Diabetes through Identical Molecular Targets in Different Cell Types.

Research in the field of pharmacology aims to generate new treatments for pathologies. Nowadays, there are an increased number of chronic disorders that severely and durably handicap many patients. Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people. For years, these pathologies have been so frequently observed in the population in a concomitant way that they are considered as comorbidities. In fact, common mechanisms are certainly at work in the etiology of these pathologies. The main purpose of this review is to show the value of anticipating the effect of baseline treatment of a condition on its comorbidity in order to obtain concomitant positive actions. One of the implications would be that by understanding and targeting shared molecular mechanisms underlying these conditions, it may be possible to tailor drugs that address both simultaneously. To this end, we firstly remind readers of the close link existing between depression and diabetes and secondly address the potential benefit of the pleiotropic actions of two major active molecules used to treat central and peripheral disorders, first a serotonin reuptake inhibitor (Prozac ®) and then GLP-1R agonists. In the second part, by discussing the therapeutic potential of new experimental antidepressant molecules, we will support the concept that a better understanding of the intracellular signaling pathways targeted by pharmacological agents could lead to future synergistic treatments targeting solely positive effects for comorbidities.

When phonological neighbours cooperate during spoken sentence processing.

This study examined for the first time the impact of the presence of a phonological neighbour on word recognition when the target word and its neighbour co-occur in a spoken sentence. To do so, we developed a new task, the verb detection task, in which participants were instructed to respond as soon as they detected a verb in a sequence of words, thus allowing us to probe spoken word recognition processes in real time. We found that participants were faster at detecting a verb when it was phonologically related to the preceding noun than when it was phonologically unrelated. This effect was found with both correct sentences (Experiment 1) and with ungrammatical sequences of words (Experiment 2). The effect was also found in Experiment 3 where adjacent phonologically related words were included in the non-verb condition (i.e., word sequences not containing a verb), thus ruling out any strategic influences. These results suggest that activation persists across different words during spoken sentence processing such that processing of a word at position n + 1 benefits from the sublexical phonology activated during processing of the word at position n. We discuss how different models of spoken word recognition might be able (or not) to account for these findings.

Does accentual variation in the pronunciation of French words influence their recognition? It depends on the ear of presentation.

This repetition priming study examined how word accentual variation in French is represented and processed during spoken word recognition. Mismatched primes in the accentual pattern were less effective than matched primes in facilitating target word recognition when the targets were presented in the left ear but not in the right ear. This indicates that in French, the accentual pattern of words influences their recognition when processing is constrained in the right hemisphere. This study pleads in favor of two memory systems, the one retaining words in an abstract format and the other retaining words in their various forms.

Effects of consonant-vowel status on transposed-phoneme priming.

Nonwords created by transposing two phonemes of auditory words (e.g., /buʒãle/) are more effective primes for the corresponding base word target (/bulãʒe/) than nonword primes created by substituting two phonemes (e.g., /buvãʀe/). In one in-lab experiment and one online experiment using the short-term phonological priming paradigm, here, we examine the role of vowels and consonants in driving transposed-phoneme priming effects. Results showed that facilitatory transposed-phoneme priming occurs when the transposed phonemes are consonants (/buʒãle/-/bulãʒe/; /lubãʒe/-/bulãʒe/), but not when they are vowels (/bãluʒe/-/bulãʒe/; /buleʒã/-/bulãʒe/). These results add to existing findings showing differences in the processing of vowels and consonants during spoken and visual word recognition. We suggest that differences in the speed of processing of consonants and vowels combined with differences in the amount of information provided by consonants and vowels relative to the identity of the word being recognized provide a complete account of the present findings.

Rime Priming Effects in Spoken Word Recognition.

In this study, we re-examined the facilitation that occurs when auditorily presented monosyllabic primes and targets share their final phonemes, and in particular the rime (e.g., /vɔʀd/-/kɔʀd/). More specifically, we asked whether this rime facilitation effect is also observed when the two last consonants of the rime are transposed (e.g., /vɔʀd/-/kɔʀd/). In comparison to a control condition in which the primes and the targets were unrelated (e.g., /pylt/-/kɔʀd/), we found significant priming effects in both the rime (/vɔdʀ/-/kɔʀd/) and the transposed-phoneme "rime" /vɔdʀ/-/kɔʀd/ conditions. We also observed a significantly greater priming effect in the former condition than in the latter condition. We use the theoretical framework of the TISK model (Hannagan et al., 2013) to propose a novel account of final overlap phonological priming in terms of activation of both position-independent phoneme representations and bi-phone representations.

Transposed-word effects in speeded grammatical decisions to sequences of spoken words.

We used the grammatical decision task (a speeded version of the grammaticality judgment task) with auditorily presented sequences of five words that could either form a grammatically correct sentence or an ungrammatical sequence. The critical ungrammatical sequences were either formed by transposing two adjacent words in a correct sentence (transposed-word sequences: e.g., "The black was dog big") or were matched ungrammatical sequences that could not be resolved into a correct sentence by transposing any two words (control sequences: e.g., "The black was dog slowly"). These were intermixed with an equal number of correct sentences for the purpose of the grammatical decision task. Transposed-word sequences were harder to reject as being ungrammatical (longer response times and more errors) relative to the ungrammatical control sequences, hence attesting for the first time that transposed-word effects can be observed in the spoken language version of the grammatical decision task. Given the relatively unambiguous nature of the speech input in terms of word order, we interpret these transposed-word effects as reflecting the constraints imposed by syntax when processing a sequence of spoken words in order to make a speeded grammatical decision.

Investigating the locus of transposed-phoneme effects using cross-modal priming.

In this study, we examined whether the facilitatory priming effect found when auditory primes and targets are related by a phoneme transposition (e.g., /ʀͻb/-/bͻʀ/: Dufour & Grainger, 2019, 2020) is also observed under cross-modal presentation. In two experiments using the same materials as in the previous studies, we found no evidence for a facilitatory priming effect when the targets were presented visually rather than auditorily. On the contrary, an inhibitory priming effect was found when both unrelated words (Experiment 1; e.g., /mas/-/bͻR/) and vowel overlap words (Experiment 2; e.g., /vͻl/-/bͻʀ/) were used as control conditions. In Experiment 2, this inhibitory effect was found to be equivalent in size whether the target words were of higher or lower frequency than the prime words (e.g. /ʀͻb/-/bͻʀ/ vs. /bͻʀ/-/ʀͻb/). We interpret this pattern of effects as reflecting the greater impact of word-level inhibition in cross-modal priming, and the parallel influence of prime-target relative frequency on bottom-up phoneme-to-word facilitation and word-level inhibition. Therefore, the facilitatory priming effect previously observed with auditory primes and targets would mainly reflect bottom-up activation of the target word representation during prime word processing.

Linotrins: Omega-3 oxylipins featuring an E,Z,E conjugated triene motif are present in the plant kingdom and alleviate inflammation in LPS-challenged microglial cells.

Alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid found in plants, exerts neuroprotection and anti-inflammatory effects in chronic and acute CNS disease models. However, the underlying mechanisms are not yet understood. Since ALA is not incorporated into the brain, the observed health benefits may result from some of its metabolites. The putative formation of dihydroxylated ALA derivatives (called linotrins) was recently shown in vitro in the presence of lipoxygenases. However, the in vitro biosynthesis of linotrins was neither stereoselective nor quantitatively efficient for studying their physiological roles as enantiomeric pure forms. Herein, we report the first stereo-controlled synthesis that features regio- and stereoselective hydrometalations of alkynes for assembling the sensitive E,Z,E-conjugated trienes, as well as LC-MS investigations that provide evidence of linotrins occurrence in plants. Moreover, strong anti-inflammatory effects on microglia highlight the potential physiological importance of linotrins and open new perspectives in search of CNS therapeutics.

Phonological abstraction before lexical access: New evidence from rime priming.

In this study, we focused on the rime priming effect and examined whether the frequency of rimes influences the size of the effect. Using the lexical decision task, we observed that the rime priming effect interacted with rime frequency with a stronger priming effect when the target words contained low-frequency rimes, in comparison with target words containing high-frequency rimes. Moreover, for both target words with low- and high-frequency rimes, a priming effect of similar magnitude was observed whether the primes and targets were pronounced by the same speaker or by different speakers. All together, these findings provide additional support for all the studies that plead for the existence of prelexical units and, in a more general way, for phonological abstraction prior to lexical access.

When you hear /baksɛt/ do you think /baskɛt/? Evidence for transposed-phoneme effect with multisyllabic words.

In this study we asked whether nonwords created by transposing two phonemes (/biksɔt/) are perceived as being more similar to their base words (/biskɔt/) than nonwords created by substituting two phonemes (/bipfɔt/). Using the short-term phonological priming and a lexical-decision task, Experiment 1 showed that transposed-phoneme nonword primes lead to shorter RTs on the target base words than substituted-phoneme nonword primes. Using a single-presentation lexical-decision task, Experiment 2 showed that transposed-phoneme nonwords lead to longer "no" decision responses than substituted-phoneme nonwords. In both Experiments 1 and 2, the transposed-phoneme effect was observed when the transposed phonemes were adjacent (/biksɔt/-/biskɔt/) but not when they were distant (/ʃoloka/-/ʃokola/). Our findings suggest that nonwords created by transposing adjacent phonemes in real words generate more activation of the lexical representations associated with the base words than do matched control nonwords. More generally, our findings present a challenge for models of spoken word recognition that code for the precise order of speech segments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Same Ultra-Rapid Parallel Brain Dynamics Underpin the Production and Perception of Speech.

The temporal dynamics by which linguistic information becomes available is one of the key properties to understand how language is organized in the brain. An unresolved debate between different brain language models is whether words, the building blocks of language, are activated in a sequential or parallel manner. In this study, we approached this issue from a novel perspective by directly comparing the time course of word component activation in speech production versus perception. In an overt object naming task and a passive listening task, we analyzed with mixed linear models at the single-trial level the event-related brain potentials elicited by the same lexico-semantic and phonological word knowledge in the two language modalities. Results revealed that both word components manifested simultaneously as early as 75 ms after stimulus onset in production and perception; differences between the language modalities only became apparent after 300 ms of processing. The data provide evidence for ultra-rapid parallel dynamics of language processing and are interpreted within a neural assembly framework where words recruit the same integrated cell assemblies across production and perception. These word assemblies ignite early on in parallel and only later on reverberate in a behavior-specific manner.

Do you want /ʃoloka/ on a /bistɔk/? On the scope of transposed-phoneme effects with non-adjacent phonemes.

We conducted two lexical decision experiments and one replication study to examine the scope of transposed-phoneme effects when the transposition involves non-adjacent phonemes. The critical stimuli were non-words derived from a real word (the base-word) either by transposing two phonemes or by substituting the same phonemes with different phonemes. In Experiment 1, the transposed phonemes belonged either to the same syllable (e.g. /bis.tɔk/ for the French base-word /bis.kɔt/) or to a different syllable (e.g. /ʃo.lo.ka/ for the French base-word /ʃo.ko.la/) and were located either at the beginning of the speech signal (e.g. /sib.kɔt/ for /bis.kɔt/; /ko.ʃo.la/ for /ʃo.ko.la/) or at the end (e.g. /bis.tɔk/ for /bis.kɔt/; /ʃo.lo.ka/ for /ʃo.ko.la/). Experiment 2 compared within-syllable and between-syllable transpositions derived from the same set of bi-syllabic base-words (e.g., /sib.kɔt/, /bik.sɔt/, /bis.tɔk/ for the base-word /biskɔt/). In both experiments, we found clear transposed-phoneme effects with longer "no" decisions for transposed-phoneme non-words compared with the matched substituted-phoneme non-words. The effect was of similar magnitude when the transposed phonemes occurred in the same syllable and across different syllables. Also, for both the within- and between-syllable transpositions, the size of the transposed-phoneme effect did not vary as a function of the position of the transposition. Overall, our results suggest that phonemes can migrate across their respective positions not only within a syllable, but also across syllables. More importantly, they also suggest that position-independent phonemes exert a continuous influence during the entire processing of the auditory stimulus to the extent that there is sufficient time for this influence to manifest itself.

Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathway.

Deterioration of insulin secretion and pancreatic beta-cell mass by inflammatory attacks is one of the main pathophysiological features of type 2 diabetes (T2D). Therefore, preserving beta-cell mass and stimulating insulin secretion only in response to glucose for avoiding the hypoglycemia risks, are the most state-of-the-art option for the treatment of T2D. In this study we tested two correlated hypothesis that 1/ the endogenous peptide released from sortilin, known as PE, that stimulates insulin secretion only in response to glucose, protects beta-cells against death induced by cytokines, and 2/ Spadin and Mini-Spadin, two synthetic peptides derived from PE, that mimic the effects of PE in insulin secretion, also provide beneficial effect on beta-cells survival. We show that PE and its derivatives by inducing a rise of intracellular calcium concentration by depolarizing the membrane protect beta-cells against death induced by Interleukin-1ß. Using biochemical, confocal imaging and cell biology techniques, we reveal that the protective effects of PE and its derivatives rely on the activation of the CaM-Kinase pathway, and on the phosphorylation and activation of the transcription factor CREB. In addition, Mini-Spadin promotes beta-cell proliferation, suggesting its possible regenerative effect. This study highlights new possible roles of PE in pancreatic beta-cell survival and its derivatives as pharmacological tools against diabetes.

Therapeutic potential of prenylated stilbenoid macasiamenene F through its anti-inflammatory and cytoprotective effects on LPS-challenged monocytes and microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Macaranga Thou. (Euphorbiaceae) is a large genus that comprises over 300 species distributed between Western Africa and the islands of the South Pacific. Plants of this genus have a long-standing history of use in traditional medicine for different purposes, including the treatment of inflammation. Fresh and dried leaves of certain Macaranga species (e.g. M. tanarius (L.) Müll.Arg.), have been used to treat cuts, bruises, boils, swellings, sores and covering of wounds in general. Several reports described Macaranga spp. being a rich source of polyphenols, such as prenylated stilbenoids and flavonoids, mostly responsible for its biological activity. Similarly, an abundant content of prenylated stilbenes was also described in M. siamensis S.J.Davies, species recently identified (2001) in Thailand. While the respective biological activity of the prenylated stilbenes from M. siamensis was poorly investigated to date, our recent study pointed out the interest as the natural source of several novel anti-inflammatory stilbenoids isolated from this species. AIM OF THE STUDY: This work investigated the potential anti-inflammatory effects of the stilbenoid macasiamenene F (MF) isolated from M. siamensis S.J.Davies (Euphorbiaceae) on the lipopolysaccharide (LPS)-induced inflammation-like response of monocytes and microglia, major cells involved in the peripheral and central inflammatory response, respectively. MATERIALS AND METHODS: LPS-induced stimulation of TLR4 signaling led to the activation of inflammatory pathways in in vitro models of THP-1 and THP-1-XBlue™-MD2-CD14 human monocytes, BV-2 mouse microglia, and an ex vivo model of brain-sorted mouse microglia. The ability of the stilbenoid MF to intervene in the IкB/NF-кB and MAPKs/AP-1 inflammatory cascade was investigated. The gene and protein expressions of the pro-inflammatory cytokines IL-1ß and TNF-α were evaluated at the transcription and translation levels. The protective effect of MF against LPS-triggered microglial loss was assessed by cell counting and the LDH assay. RESULTS: MF demonstrated beneficial effects, reducing both monocyte and microglial inflammation as assessed in vitro. It efficiently inhibited the degradation of IкBα, thereby reducing the NF-кB activity and TNF-α expression in human monocytes. Furthermore, the LPS-induced expression of IL-1ß and TNF-α in microglia was dampened by pre-, co-, or post-treatment with MF. In addition to its anti-inflammatory effect, MF demonstrated a cytoprotective effect against the LPS-induced death of BV-2 microglia. CONCLUSION: Our research into anti-inflammatory and protective effects of MF has shown that it is a promising candidate for further in vitro and in vivo investigations of MF interventions with respect to acute and chronic inflammation, including potentially beneficial effects on the inflammatory component of brain diseases such as stroke and Alzheimer's disease.

The influence of word frequency on the transposed-phoneme priming effect.

Speech input like [byt] has been shown to facilitate not only the subsequent processing of an identical target word /byt/ but also that of a target word /tyb/ that contains the same phonemes in a different order. Using the short-term phonological priming paradigm, we examined the role of lexical representations in driving the transposed-phoneme priming effect by manipulating lexical frequency. Results showed that the transposed-phoneme priming effect occurs when targets have a higher frequency than primes, but not when they have a lower frequency. Our findings thus support the view that the transposed-phoneme priming effect results from partial activation of the target word's lexical representation during prime processing. More generally, our study provides further evidence for a role for position-independent phonemes in spoken word recognition.

Are Prosodic Variants Stored in the French Mental Lexicon?

A long-term priming experiment examined the way stress information is processed and represented in French speakers' mind. Repeated prime and target words either matched (/bã'do/ - /bã'do/ "headband") or mismatched their stress pattern (/bãdo/ - /bã'do/). In comparison to a control condition (/maʁ[Formula: see text]/ - /bã'do/), the results showed that matching and mismatching primes were equally effective in facilitating the processing of the target words. Thus, despite the fact that French speakers routinely produce and hear words in their stressed and unstressed versions, this study suggests that stress in French is not integrated into lexical representations.

Phoneme-Order Encoding During Spoken Word Recognition: A Priming Investigation.

In three experiments, we examined priming effects where primes were formed by transposing the first and last phoneme of tri-phonemic target words (e.g., /byt/ as a prime for /tyb/). Auditory lexical decisions were found not to be sensitive to this transposed-phoneme priming manipulation in long-term priming (Experiment 1), with primes and targets presented in two separated blocks of stimuli and with unrelated primes used as control condition (/mul/-/tyb/), while a long-term repetition priming effect was observed (/tyb/-/tyb/). However, a clear transposed-phoneme priming effect was found in two short-term priming experiments (Experiments 2 and 3), with primes and targets presented in close temporal succession. The transposed-phoneme priming effect was found when unrelated prime-target pairs (/mul/-/tyb/) were used as control and more important when prime-target pairs sharing the medial vowel (/pys/-/tyb/) served as control condition, thus indicating that the effect is not due to vocalic overlap. Finally, in Experiment 3, a transposed-phoneme priming effect was found when primes sharing the medial vowel plus one consonant in an incorrect position with the targets (/byl/-/tyb/) served as control condition, and this condition did not differ significantly from the vowel-only condition. Altogether, these results provide further evidence for a role for position-independent phonemes in spoken word recognition, such that a phoneme at a given position in a word also provides evidence for the presence of words that contain that phoneme at a different position.

Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets.

Diabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies. The increase in number of diabetic people, incidence of stroke in the presence of this specific risk factor, and the exacerbation of ischemic brain damage in diabetic conditions (at least in animal models) warrants the need to integrate this comorbidity in preclinical studies of brain ischemia to develop novel therapeutic approaches. Therefore, a better understanding of the commonalties involved in the course of both diseases would offer the promise of discovering novel neuroprotective pathways that would be more appropriated to clinical scenarios. In this article, we will review the relevant mechanisms that have been identified as common traits of both pathologies and that could be, to our knowledge, potential targets in both pathologies.