A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering

Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presen ce of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech. © 2012 Wiley Periodicals, Inc

Brain activation during non-habitual speech production: Revisiting the effects of simulated disfluencies in fluent speakers

Over the past decades, brain imaging studies in fluently speaking participants have greatly advanced our knowledge of the brain areas involved in speech production. In addition, complementary information has been provided by investigations of brain activation patterns associated with disordered speech. In the present study we specifically aimed to revisit and expand an earlier study by De Nil and colleagues, by investigating the effects of simulating disfluencies on the brain activation patterns of fluent speakers during overt and covert speech production. In contrast to the De Nil et al. study, the current findings show that the production of voluntary, self-generated disfluencies by fluent speakers resulted in increased recruitment and activation of brain areas involved in speech production. These areas show substantial overlap with the neural networks involved in motor sequence learning in general, and learning of speech production, in particular. The implications of these findings for the interpretation of brain imaging studies on disordered and non-habitual speech production are discussed

Ontwikkeling van stotteren: Inleiding tot een praktijkmodel

Dit artikel is de inleiding op het direct hierna volgende (Oonk e.a. 2022) waar een nieuw praktijkmodel over het ontstaan en ontwikkeling van stotteren wordt voorgesteld. In de dagelijkse praktijk van vooral Nederlandstalige logopedisten (-stottertherapeuten) is tot nu toe veel gebruik gemaakt van het klinische werkmodel van Bertens (1994; 2017). Dit model gaat uit van een primaire neuromusculaire timingsstoornis, welke zich niet alleen uit in het spreken, maar ook in algemene zin aanwezig is. Dit model echter, is aan revisie toe. Volgens de recente literatuur is de algemene aard van die timingstoornis niet bewezen, en zijn er veel vroegere (meer primaire) factoren aantoonbaar van belang bij het ontstaan van stotteren, met name in de genetica en in de neurologie. In dit artikel wordt deze literatuur kort samengevat, alsmede worden enkele recente modellen omschreven. Met name regulatie en terugkoppeling krijgen in recente modellen meer aandacht. Er is geen volledigheid nagestreefd, maar dit artikel is meer een tutoriale opmaat voor het hierna te presenteren model. (This article serves as an introduction to the accompanying paper, in which a new clinical model of the origin and development of stuttering is presented (Oonk e.a., 2022). In their clinical practice, Dutch speech language pathologists still tend to use the clinical model proposed by Bertens (1994; 2017). This model explains stuttering as de- veloping from a primary neuromuscular timing deficit, which manifests itself not only in speech, but in more general behaviour as well. In our opinion, this model needs to be updated and revised based on current scientific and clinical knowledge. There is littleevidence for the general timing deficit in Bertens’ model and, moreover, several more fundamental factors, especially those related to genetics and neural processes, that have an important role in the onset of stuttering have been reported. This paper provides a review and summary of these recent data, and several newer models are described. An important aspect of these models is the importance given to processes of regulation and feedback. An exhaustive overview of the existing literature has not been strived for but it is hoped that this paper will serve as a useful introduction to the clinical model presented in the accompanying paper.

A fNIRS investigation of speech planning and execution in adults who stutter

Our study aimed to determine the neural correlates of speech planning and execution in adults who stutter (AWS). Fifteen AWS and 15 controls (CON) completed two tasks that either manipulated speech planning or execution processing loads. Functional near-infrared spectroscopy (fNIRS) was used to measure changes in blood flow concentrations during each task, thus providing an indirect measure of neural activity. An image-based reconstruction technique was used to analyze the results and facilitate their interpretation in the context of previous functional neuroimaging studies of AWS that used positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). For planning, we compared neural activity associated with high versus low planning load in AWS and CON. For execution, we compared the neural activity associated with overt versus covert naming in AWS and CON. Broadly, group level effects corroborate previous PET/fMRI findings including under-activation in lefthemisphere perisylvian speech-language networks and over-activation in righthemisphere homologues. Increased planning load revealed atypical left-hemisphere activation in AWS, whereas increased execution load yielded atypical right frontotemporo-parietal and bilateral motor activation in AWS. Our results add to the limited literature differentiating speech planning versus execution processes in AWS

The effects of financialisation and financial development on investment: Evidence from firm-level data in Europe

In this paper we estimate the effects of financialization on physical investment in selected western European countries using panel data based on the balance-sheets of publicly listed non-financial companies (NFCs) supplied by Worldscope for the period 1995-2015. We find robust evidence of an adverse effect of both financial payments (interests and dividends) and financial incomes on investment in fixed assets by the NFCs. This finding is robust for both the pool of all Western European firms and single country estimations. The negative impacts of financial incomes are non-linear with respect to the companies’ size: financial incomes crowd-out investment in large companies, and have a positive effect on the investment of only small, relatively more credit-constrained companies. Moreover, we find that a higher degree of financial development is associated with a stronger negative effect of financial incomes on companies’ investment. This finding challenges the common wisdom on ‘finance-growth nexus’. Our findings support the ‘financialization thesis’ that the increasing orientation of the non-financial sector towards financial activities is ultimately leading to lower physical investment, hence to stagnant or fragile growth, as well as long term stagnation in productivity

Analysis of MEFV exon methylation and expression patterns in familial Mediterranean fever

<p>Abstract</p> <p>Background</p> <p>MEFV mutations and decreased expression level of the gene are related to FMF pathology. DNA methylation at CpG islands is a well-known mechanism for transcriptional silencing. MEFV has a CpG island, spanning a part of the first intron and the whole of the second exon of the gene covering 998 bp region. Here, we tested the hypothesis that the MEFV transcript level in FMF patients correlates with its methylation level, and methylation, by allowing transcription silencing, has a role in FMF ethiopathogenesis.</p> <p>Methods</p> <p>The study group was composed of pediatric FMF patients (N = 51) and age-gender matched healthy controls (N = 21). The relative expression level of MEFV was assessed via quantitative real-time PCR (qRT-PCR) and bisulfite sequencing (BS) was performed to analyse the methylation level quantitatively.</p> <p>Results</p> <p>MEFV expression in FMF patients were decreased compared to healthy controls (<it>P </it>= 0.031). Methylation level of exon 2 of MEFV was found to be slightly higher in FMF patients compared to healthy controls (76% versus 74%) (<it>P </it>= 0.049). The expression level of the MEFV was negatively correlated with the methylation level of the CpG island in both FMF and healthy controls groups (cor = -0.29, <it>P </it>= 0.041) but more so in the FMF only group (cor = -0.36, <it>P </it>= 0.035).</p> <p>Conclusions</p> <p>In this study, the relation between reduced MEFV expression level and FMF was confirmed. Observed slight increase in methylation in FMF patients, and correlation of methylation with expression might be indicative of its role in FMF, however a larger dataset is needed to confirm our preliminary findings.</p

Resting-State Brain Activity in Adult Males Who Stutter

Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them

Weak Responses to Auditory Feedback Perturbation during Articulation in Persons Who Stutter: Evidence for Abnormal Auditory-Motor Transformation

Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking) functions abnormally in the speech motor systems of persons who stutter (PWS). Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants’ compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls’ and had close-to-normal latencies (~150 ms), but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05). Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands

Classification of Types of Stuttering Symptoms Based on Brain Activity

Among the non-fluencies seen in speech, some are more typical (MT) of stuttering speakers, whereas others are less typical (LT) and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT) whole-word repetitions (WWR) should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type

Readout electronics for LGAD sensors

In this paper, an ASIC fabricated in 180 nm CMOS technology from AMS with the very front-end electronics used to readout LGAD sensors is presented as well as its experimental results. The front-end has the typical architecture for Si-strip readout, i.e., preamplification stage with a Charge Sensitive Amplifier (CSA) followed by a CR-RC shaper. Both amplifiers are based on a folded cascode structure with a PMOS input transistor and the shaper only uses passive elements for the feedback stage. The CSA has programmable gain and a configurable input stage in order to adapt to the different input capacitance of the LGAD sensors (pixelated, short and long strips) and to the different input signal (depending on the gain of the LGAD). The fabricated prototype has an area of 0.865 mm × 0.965 mm and includes the biasing circuit for the CSA and the shaper, 4 analog channels (CSA+shaper) and programmable charge injection circuits included for testing purposes. Noise and power analysis performed during simulation fixed the size of the input transistor to W/L = 860 μm/0.2 μm. The shaping time is fixed by design at 1 us and, in this ASIC version, the feedback elements of the shaper are passive, which means that the area of the shaper can be reduced using active elements in future versions. Finally, the different gains of the CSA have been selected to maintain an ENC below 400 electrons for a detector capacitor of 20 pF, with a power consumption of 150 μ W per channel