Developmental stuttering (DS) is a disturbance of the normal rhythm of speech that may be interpreted as very debilitating in the most affected cases. Interventions for DS are historically based on ...the behavioral modifications of speech patterns (e.g., through speech therapy), which are useful to regain a better speech fluency. However, a great variability in intervention outcomes is normally observed, and no definitive evidence is currently available to resolve stuttering, especially in the case of its persistence in adulthood. In the last few decades, DS has been increasingly considered as a functional disturbance, affecting the correct programming of complex motor sequences such as speech. Compatibly, understanding of the neurophysiological bases of DS has dramatically improved, thanks to neuroimaging, and techniques able to interact with neural tissue functioning e.g., non-invasive brain stimulation (NIBS). In this context, the dysfunctional activity of the cortico-basal-thalamo-cortical networks, as well as the defective patterns of connectivity, seems to play a key role, especially in sensorimotor networks. As a consequence, a direct action on the functionality of "defective" or "impaired" brain circuits may help people who stutter to manage dysfluencies in a better way. This may also "potentiate" available interventions, thus favoring more stable outcomes of speech fluency. Attempts aiming at modulating (and improving) brain functioning of people who stutter, realized by using NIBS, are quickly increasing. Here, we will review these recent advancements being applied to the treatment of DS. Insights will be useful not only to assess whether the speech fluency of people who stutter may be ameliorated by acting directly on brain functioning but also will provide further suggestions about the complex and dynamic pathophysiology of DS, where causal effects and "adaptive''/''maladaptive" compensation mechanisms may be strongly overlapped. In conclusion, this review focuses future research toward more specific, targeted, and effective interventions for DS, based on neuromodulation of brain functioning.
•Developmental stuttering (DS) relies on dysfunctional neural exchange: the supplementary motor area (SMA) may play a key role.•We used combined TMS/EEG to investigate functional connectivity of the ...SMA “complex” in DS.•Abnormal neural timing in DS is inferred which helps to understand the pathophysiology of DS and develop new treatments.
Brain dynamics in developmental stuttering (DS) are not well understood. The supplementary motor area (SMA) plays a crucial role, since it communicates with regions related to planning/execution of movements, and with sub-cortical regions involved in paced/voluntary acts (such as speech). We used TMS combined with EEG to shed light on connections in DS, stimulating the SMA.
TMS/EEG was recorded in adult DS and fluent speakers (FS), stimulating the SMA during rest. TMS-evoked potentials and source distribution were evaluated.
Compared to FS, stutterers showed lower activity of neural sources in early time windows: 66–82 ms in SMA, and 91–102 ms in the left inferior frontal cortex and left inferior parietal lobule. Stutterers, however, showed higher activations in later time windows (i.e. from 260–460 ms), in temporal/premotor regions of the right hemisphere.
These findings represent the functional counterpart to known white matter and cortico-basal-thalamo-cortical abnormalities in DS. They also explain how white matter abnormalities and cortico-basal-thalamo-cortical dysfunctions may be associated in DS. Finally, a mechanism is proposed in which compensatory activity of the non-dominant (right) hemisphere is recruited.
DS may be a disorder of neural timing that appears to be delayed compared to FS; new mechanisms that support stuttering symptoms are inferred; the SMA may be a promising target for neuro-rehabilitation.
Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS ...adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a "state" condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge's g or Cohen's dunbiased = 1.054, i.e. large effect size), suggesting a "state" condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering "state" in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).
In fibromyalgia syndrome (FMS), the Rességuier Method (RM) and Qi Gong (QG) can be efficacious. QG aims to improve posture, respiration, concentration, while RM aims to obtain patient awareness and ...control of pain perception. We evaluate 2 protocols integrating RM and QG in FMS.
Thirty FMS patients were assigned to Group 1, treated by RM and then by QG or Group 2, treated by QG and then by RM. In both protocols, patients are treated 7 weeks by each technique (with 1 week interval), and followed up for 12 weeks. Patients were assessed at T0, at end of 1st (T1) and 2nd intervention (T2), at follow-up (FU) by number rating scale (NRS) for sleep quality and pain, Regional Pain Scale (RPS),Tender Points (TPs), FIQ, HAQ, SF36, HADS for anxiety and depression (HADS-a/d).
In Group 1 at T1 (after RM), NRS for pain, RPS, FIQ, HAQ were reduced, HADS-a and SF36 ameliorated; at T2 (after QG) FIQ were further reduced and TPs and HADS-d improved; HADS-a and SF36 maintained. In Group 2 at T1 (after QG), NRS for pain, RPS, TPs, FIQ, HAQ, reduced with reduction maintained at T2 (after RM). HADS-a and -d and SF36 ameliorated at T1, with improvement confirmed at T2; sleep quality ameliorated only at T2. Effects of both protocols are similar at T2 and maintained at FU.
In FMS, both protocols improve pain, disability, quality of life, tenderness, anxiety. RM also ameliorates sleep and QG improves depression. Sequential integration of RM and QG is efficacious in FMS.
Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological ...factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available.
Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks.
The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks.
The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.
•The influence of muscle representations on “surrounding” ones, in stuttering, was investigated.•Enhanced intracortical inhibition of the motor cortex was evident, especially during “externally-cued” ...movements.•Higher inhibition of muscles not involved in movements may be used by stutterers to obtain efficient motor control.
Previous studies regarding developmental stuttering (DS) suggest that motor neural networks are strongly affected. Transcranial magnetic stimulation (TMS) was used to investigate neural activation of the primary motor cortex in DS during movement execution, and the influence of muscle representations involved in movements on “surrounding” ones. TMS was applied over the contralateral abductor digiti minimi (ADM) motor representation, at rest and during the movement of homologue first dorsal interosseous muscles (tonic contraction, phasic movements cued by acoustic signalling, and “self-paced” movements). Results highlighted a lower cortico-spinal excitability of ADM in the left hemisphere of stutterers, and an enhanced intracortical inhibition in their right motor cortex (in comparison to fluent speakers). Abnormal intracortical functioning was especially evident during phasic contractions cued by “external” acoustic signals. An exaggerated inhibition of muscles not directly involved in intended movements, in stuttering, may be useful to obtain more efficient motor control. This was stronger during contractions cued by “external” signals, highlighting mechanisms likely used by stutterers during fluency-evoking conditions.
Abstract Background Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to ...examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available. Methods Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks. Results The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks. Conclusion The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.
Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration ...after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1-dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K-phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2-PI3K-p-Akt signalling pathway.
This paper validates the use of a harmonic analysis algorithm on a microcontroller to perform measurements of non-stationary signals in the context of smart grids. The increasing presence of ...electronic devices such as inverters of distributed generators (DG), power converters of charging stations for electric vehicles, etc. can drain non-stationary currents during their operation. A classical fast Fourier transform (FFT) algorithm may not have sufficient spectral resolution for the evaluation of harmonics and inter-harmonics. Thus, in this paper, the implementation of a chirp-Z transform (CZT) algorithm is suggested, which has a spectral resolution independent from the observation window. The CZT is implemented on a low-cost commercial microcontroller, and the absolute error is evaluated with respect to the same algorithm implemented in the LabVIEW environment. The results of the tests show that the CZT implementation on a low-cost microcontroller allows for accurate measurement results, demonstrating the feasibility of reliable harmonic analysis measurements even in non-stationary conditions on smart grids.
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