Neurophysiological aspects of speech perception and production in stuttering

Stuttering is a speech disorder in which the smooth succession of speech sounds is interrupted by frequent blocks, prolongations and/or repetitions of sounds or syllables. When stuttering manifests itself for the first time during childhood, it is called developmental stuttering. When stuttering is of non-developmental origin, it is referred to as acquired stuttering. Acquired stuttering mostly derives from damage to the central nervous system which is called neurogenic stuttering. Neurologically, stuttering is characterized by alterations in cortical and subcortical brain regions related to speech motor planning, initiation, execution and monitoring. Neurological research in stuttering contains a plethora of spatial neuroimaging studies (e.g. fMRI) but a dearth of neurophysiological studies, especially when it comes to speech motor control. However, fluent speech does not only require the appropriate amount of (de)activation of specific brain regions, it also needs a timely and precise coordination of these brain regions. Therefore, the present thesis aimed to identify neurophysiological characteristics of speech motor control in stuttering by the use of electro-encephalography. First, temporal coordination of motor related activity during a visual word recognition task was assessed. Time points of motor related activity during hand action and non-action verb processing were compared in a group of fluent speakers and a group of adults with developmental stuttering. Secondly, speech motor preparatory activity preceding single word production was measured in real time by evoking a contingent negative variation (CNV) during a picture naming task. The CNV is an event-related potential reflecting motor preparatory activity in the basal ganglia-thalamo-cortical – loop. Speech motor preparation was compared between fluent speakers, and both fluent and stuttered words of stuttering speakers. Thirdly, although developmental and neurogenic stuttering are suggested to share common neural substrates, both types of stuttering were compared to assess whether this also accounts for speech motor preparatory activity. To that purpose, the same CNV picture naming task was performed in a case of neurogenic stuttering. Timing of motor related activation was considerable altered in the stuttering group, even during a silent reading task without (speech) movement requirements. The time point of maximal motor difference between both verb types was delayed with 100 ms and showed a reversed activation pattern compared to that of fluent speakers. This reversal is hypothesized to encompass two different motor abnormalities: a general motor hyperactivation, presenting during non-action verb processing, and a specific hand motor deficit, causing decreased excitability of this region during hand action verb processing. These findings confirm that temporal alterations in neural motor activations in stuttering are not restricted to overt speech production. Secondly, speech motor preparatory activity generated by the basal ganglia-thalamo-cortical – loop was found to have a crucial role in stuttering. Not only has its amount of activation a determining role in the actual moment of a stutter, its activation seems also related to the underlying stuttering pathology. An important divergence between left and right hemisphere is seen in this respect. When motor preparatory activity in right basal ganglia-thalamo-cortical – loop is markedly increased, no stutter will occur. The more frequent and/or the more severe a person stutters, the higher this increase is or must be to enable fluent speech production. The lower the motor preparatory activity preceding a stutter in the left basal ganglia-thalamo-cortical – network, the more this person will stutter in general. As such, left basal ganglia-thalamo-cortical – loop is suggested to have a link with the stuttering pathology. These findings concur with a growing amount of studies stating that right hemisphere alterations are related to (successful) compensation strategies, while the left hemisphere would contain the primary cause of stuttering. Thirdly, important differences emerged when comparing the findings concerning speech motor preparatory activity of the developmental stuttering group and the case with neurogenic stuttering. Roughly speaking, an increase in stuttering frequency was associated with an increase in CNV slope in the developmental stuttering group and a decrease in CNV in the case of neurogenic stuttering. Although neurogenic and developmental stuttering are believed to share common neural characteristics, these may be restricted to neuroanatomical findings. Both types of stuttering may show considerable variation in neurophysiological functioning, probably related to a difference in lesion localisation. Finally, when findings of the present studies are placed within a broader framework, the importance of the motor loop of feedforward processing in stuttering is highlighted. All observed motor alterations presented without simultaneous deficits in feedback processing or without obvious inferences of language impairments. Overall, the present thesis evidences that neurophysiology is able to discover interesting and intriguing neural findings that may aid in unravelling the enigma of stuttering

Quantitative analysis of language production in Parkinson's disease using a cued sentence generation task

The present study examined language production skills in Parkinson's disease (PD) patients. A unique cued sentence generation task was created in order to reduce demands on memory and attention. Differences in sentence production abilities according to disease severity and cognitive impairments were assessed. Language samples were obtained from 20 PD patients and 20 healthy control participants matched for age, sex and educational level. In addition, a cognitive test for verbal memory and resistance to cognitive interference was administered. Statistical comparisons revealed significant language changes in an advanced stage of the disease. Advanced PD patients showed a reduction in lexical diversity in notional verbs, which was absent in nouns. Cognitive dysfunctions such as impaired verbal memory are suggested to contribute to the typical noun/verb dissociation in PD patients. In addition, advanced PD patients produced more semantic perseverations, which may be related to set-switching problems. In conclusion, whether language disturbances in PD are the result of non-linguistic cognitive dysfunctions or reflect pure language deficits exacerbated by cognitive impairments, remains a matter of debate. However, the negative impact of cognitive dysfunctions may be important

Microbial detoxification of deoxynivalenol (DON), assessed via a Lemna minor L. bioassay, through biotransformation to 3-epi-DON and 3-epi-DOM-1

Mycotoxins are toxic metabolites produced by fungi. To mitigate mycotoxins in food or feed, biotransformation is an emerging technology in which microorganisms degrade toxins into non-toxic metabolites. To monitor deoxynivalenol (DON) biotransformation, analytical tools such as ELISA and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) are typically used. However, these techniques do not give a decisive answer about the remaining toxicity of possible biotransformation products. Hence, a bioassay using Lemna minor L. was developed. A dose-response analysis revealed significant inhibition in the growth of L. minor exposed to DON concentrations of 0.25 mg/L and higher. Concentrations above 1 mg/L were lethal for the plant. This bioassay is far more sensitive than previously described systems. The bioassay was implemented to screen microbial enrichment cultures, originating from rumen fluid, soil, digestate and activated sludge, on their biotransformation and detoxification capability of DON. The enrichment cultures originating from soil and activated sludge were capable of detoxifying and degrading 5 and 50 mg/L DON. In addition, the metabolites 3-epi-DON and the epimer of de-epoxy-DON (3-epi-DOM-1) were found as biotransformation products of both consortia. Our work provides a new valuable tool to screen microbial cultures for their detoxification capacity

Chemically versus thermally processed brown shrimp shells or Chinese mitten crab as a source of chitin, nutrients or salts and as microbial stimulant in soilless strawberry cultivation

Brown shrimp (Crangon crangon) shells and Chinese mitten crab (Efiocheir sinensis) were chemically demineralized and deproteinized (denoted as M1 to M4 for the shrimp shells and MS to M7 for the Chinese mitten crab), and shrimp shells were torrefied at 200 to 300 degrees C (denoted as R200, R255, R300), and were compared with a commercially available chitin source (denoted as reference chitin). Based on their chemical characteristics, a selection of chitin sources was tested for their N mineralization capacity. The N release was high for the chemically treated shrimp shells and Chinese mitten crab, but not for the Dandled shrimp shells with or without acid treatment, indicating that treatment at 200 et or higher resulted in low N availability. Interaction with nutrients was tested in a leaching experiment with limed peat for three thermally and two chemically processed shrimp shells and the reference chitin source. The K concentrations in the leachate for the chemically treated shrimp shells and the reference chitin were lower than for limed peat during fertigation. Irreversible K retention was observed for one source of chemically treated shrimp shells, and the reference chitin. The thermally treated shrimp shells had a significantly higher net release of P. Na and CI than the treatment without chitin source. Three shrimp shell based materials (M4, R200 and 8300) and the reference chitin were tested in a greenhouse trial with strawberry at a dose of 2 g/L limed peat. A very positive and significant effect on Borryris cinerea disease suppression in the leaves was found for the reference chitin, M4 and R200 compared to the unamended control. The disease suppression of the 3 chitin sources was linked with an increase of the microbial biomass in the limed peat with 24% to 28% due to chitin decomposition and a 9-44% higher N uptake in the plants

CoMix: comparing mixing patterns in the Belgian population during and after lockdown.

The COVID-19 pandemic has shown how a newly emergent communicable disease can lay considerable burden on public health. To avoid system collapse, governments have resorted to several social distancing measures. In Belgium, this included a lockdown and a following period of phased re-opening. A representative sample of Belgian adults was asked about their contact behaviour from mid-April to the beginning of August, during different stages of the intervention measures in Belgium. Use of personal protection equipment (face masks) and compliance to hygienic measures was also reported. We estimated the expected reproduction number computing the ratio of [Formula: see text] with respect to pre-pandemic data. During the first two waves (the first month) of the survey, the reduction in the average number of contacts was around 80% and was quite consistent across all age-classes. The average number of contacts increased over time, particularly for the younger age classes, still remaining significantly lower than pre-pandemic values. From the end of May to the end of July , the estimated reproduction number has a median value larger than one, although with a wide dispersion. Estimated [Formula: see text] fell below one again at the beginning of August. We have shown how a rapidly deployed survey can measure compliance to social distancing and assess its impact on COVID-19 spread. Monitoring the effectiveness of social distancing recommendations is of paramount importance to avoid further waves of COVID-19

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1:a multicentre, single-blind, randomised trial

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. Methods: We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep–wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10–14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0–100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered with ClinicalTrials.gov, number NCT02118779. Findings: Between April 2, 2014, and May 29, 2015, we randomly assigned 255 patients to treatment: 128 to cognitive behavioural therapy plus standard care and 127 to standard care alone. 33 (26%) of 128 assigned to cognitive behavioural therapy also received the graded exercise module. Follow-up continued until Oct 17, 2016. The DM1-Activ-c score increased from a mean (SD) of 61·22 (17·35) points at baseline to 63·92 (17·41) at month 10 in the cognitive behavioural therapy group (adjusted mean difference 1·53, 95% CI −0·14 to 3·20), and decreased from 63·00 (17·35) to 60·79 (18·49) in the standard care group (−2·02, −4·02 to −0·01), with a mean difference between groups of 3·27 points (95% CI 0·93 to 5·62, p=0·007). 244 adverse events occurred in 65 (51%) patients in the cognitive behavioural therapy group and 155 in 63 (50%) patients in the standard care alone group, the most common of which were falls (155 events in 40 [31%] patients in the cognitive behavioural therapy group and 71 in 33 [26%] patients in the standard care alone group). 24 serious adverse events were recorded in 19 (15%) patients in the cognitive behavioural therapy group and 23 in 15 (12%) patients in the standard care alone group, the most common of which were gastrointestinal and cardiac. Interpretation: Cognitive behavioural therapy increased the capacity for activity and social participation in patients with myotonic dystrophy type 1 at 10 months. With no curative treatment and few symptomatic treatments, cognitive behavioural therapy could be considered for use in severely fatigued patients with myotonic dystrophy type 1. Funding: The European Union Seventh Framework Programme