Intelligibility in Down syndrome: Effect of measurement method and listener experience.

BACKGROUND: Speech intelligibility is a global indicator of the severity of a speech problem. It is a measure that has been used frequently in research and clinical assessment of speech. Previous studies have shown that factors, such as measurement method and listener experience, can influence speech intelligibility scores. However, these factors of speech intelligibility assessment have not yet been investigated in people with Down syndrome (DS). AIMS: To compare the speech intelligibility scores in speakers with DS measured using two methods: orthographic transcription and visual analogue scale (VAS), by two groups of listeners, experienced listeners and naïve listeners. Also, to examine the relationship across the four sets of speech intelligibility scores by means of correlational analysis. METHODS & PROCEDURES: A total of 30 adolescents and adults with DS read or repeated 12 sentences from a standardized test of intelligibility for adults with dysarthria. Each sentence was saved as a separate sound file and the 360 sentences were divided to form eight sets of stimuli. A total of 32 adults (16 experienced and 16 naïve) served as listeners of speech intelligibility. Each listener heard a single set of sentences and independently estimated the level of intelligibility for each sentence using a VAS in one task and wrote down the words perceived (i.e., orthographic transcription) in another task. The order of the two tasks was counterbalanced across listeners and the tasks were completed at least 1 week apart. OUTCOMES & RESULTS: Repeated-measures analysis of variance (ANOVA), confirmed by mixed-methods analysis, showed that the scores obtained using orthographic transcription were significantly higher than those obtained using VAS; and the experienced listeners' scores were significantly higher than the naïve listeners' scores. Spearman rank correlation analysis showed that the four sets of scores across all conditions were strongly positively correlated with each other. CONCLUSIONS & IMPLICATIONS: Listeners, both experienced and naïve, may udge speech in DS differently when using orthographic transcription versus VAS as the method of measurement. In addition, experienced listeners can judge speech intelligibility differently compared with listeners who are less exposed to unclear speech, which may not represent 'real-world' functional communicative ability. Speech and language therapists should be aware of the effect of these factors when measuring intelligibility scores and direct comparison of scores obtained using different procedures and by different groups of listeners is not recommended. What this paper adds What is already known on the subject Previous research on other clinical groups (e.g., Parkinson's disease) has shown that speech intelligibility scores can vary across different measurement methods and when judged by listeners with different experience. However, these factors have not yet been investigated in people with DS. What this paper adds to existing knowledge Similar to the findings reported for other clinical groups, using an impressionistic measurement method, such as VAS, can result in different speech intelligibility scores compared with scores obtained from orthographic transcription in speakers with DS. Furthermore, experienced listeners can perceive intelligibility as better compared with naïve (untrained) listeners for this group. What are the potential or actual clinical implications of this work? When measuring speech intelligibility, speech and language therapists should be aware that scores obtained using orthographic transcription can be higher than those obtained using VAS. They should also be aware that their increased exposure to hearing atypical speech may cause them to judge the speech difficulty as less severe and lead to an inaccurate representation of speech performance. Speech and language therapists should consider these factors when interpreting assessment results and especially when using intelligibility measures for treatment outcomes.

Perceptual and acoustic evaluation of speech production in Down syndrome: A case series.

People with Down syndrome (DS) can experience difficulties with speech production that can impact on speech intelligibility. In previous research, both perceptual and acoustic analysis has shown that people with DS can have difficulties with speech production in the areas of respiration, phonation, articulation, resonance and prosody. However, these studies have investigated various aspects of speech production separately. No study has examined all components of speech production in one single study and considered how these components, if impaired, may impact on speech intelligibility in DS. This paper presents the data of three male speakers with DS and three age- and gender-matched controls as a case series. The participants' speech samples were analysed using a number of perceptual and acoustic parameters, across the major components of speech production - respiration, phonation, articulation, resonance, and prosody. Results showed that different areas of speech production were affected in each participant, to different extents. The main perceptual difficulties included poor voice quality, monopitch, and monoloudness. Acoustic findings showed a higher mean F0, lower harmonics-to-noise ratio and longer voice onset times. These preliminary findings show that people with DS can present with mixed profiles of speech production that can affect speech intelligibility. When assessing speech production in DS, clinicians need to evaluate all components of speech production and consider how they may be impacting intelligibility.

Agonists of peroxisome proliferator-activated receptor-gamma attenuate the Abeta-mediated impairment of LTP in the hippocampus in vitro.

The data we present here suggest that agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma) can attenuate the effects of beta-amyloid peptide (Abeta). Alzheimer's disease is associated with elevated levels of Abeta, and enhanced expression of PPARgamma. In this study, we determined that application of Abeta([1-40]) could impair hippocampal post-tetanic potentiation (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of PPARgamma agonists; troglitazone, ciglitazone and 15-deoxy-delta(12,14) prostaglandin J2 (PGJ2) on synaptic transmission and plasticity in area CA1. Both ciglitazone and PGJ2 increased baseline synaptic transmission significantly, without altering paired-pulse facilitation. PGJ2 produced a significant reduction in LTP, whereas ciglitazone and troglitazone had no significant effect. In addition, prior application of each ligand attenuated the previously observed Abeta([1-40])-mediated impairment of LTP. The effect of troglitazone on the Abeta([1-40])-mediated impairment of LTP was not reversed by the PPARgamma antagonist, GW-9662. These findings demonstrate that PPARgamma agonists attenuate the effects of Abeta on LTP, and support the potential use of these agents to alleviate the symptoms of Alzheimer's disease. We also suggest that PPARgamma agonists may regulate expression of hippocampal LTP in vitro.

Arterial chemoreceptors in the superior laryngeal nerve of the rat.

Paraganglia resembling the carotid body have been described in the superior laryngeal nerve (SLN) of the rat and the aim of the present study was to determine if this tissue is chemosensitive. We developed a novel isolated SLN preparation superfused with HEPES-buffered Tyrode solution at 35 degrees C in vitro. A glass suction microelectrode was used to record the electrical activity of single SLN units and a micropipette was used to pressure-eject small volumes of sodium cyanide (NaCN; 250-500 ng in 5 microl) near glomus tissue located at the main bifurcation of the SLN. The duration of the NaCN response and the number of spikes evoked after application of NaCN were compared in normoxia and hyperoxia (PO2 > 300 mmHg). Hyperoxia significantly reduced the duration and spike number of the NaCN response and a negative linear correlation existed between PO2 and response duration. In addition, hypoxia (PO2 < 60 mmHg) triggered SLN firing. Therefore, we can conclude that the paraganglia of the SLN are not only morphologically similar to the carotid body but are also excited by similar stimuli.

Discharge patterns of preganglionic neurones with axons in a cardiac vagal branch in the rat.

The fibre types that run in a vagal branch projecting to the rat heart are described in this study. In order to obtain spontaneous discharge in this vagal branch and optimal recording conditions, we compared the decerebrate state to urethane, urethane-chloralose and pentobarbital-chloralose anaesthesia with regard to level of chronotropic cardiac vagal tone. Administration of atropine (2 mg kg(-1), I.V.) significantly decreased baseline cardiac interval only in the decerebrate and urethane-anaesthetised rat (by 0.018 +/- 0.001 s and 0.019 +/- 0.002 s, respectively). As a result of these experiments, urethane was chosen as the anaesthetic for all subsequent studies. Using a heart rate signal-averaging method we demonstrated that rat cardiac vagal preganglionic neurones innervating the sinoatrial node should have an expiratory discharge pattern, as reported in other species. However, only 5 % of chronotropic vagal tone was found to be subject to respiratory sinus arrhythmia. A suction microelectrode method, combined with spike-triggered averaging, was employed to record activity from a total of 58 vagal afferents that had axons in this branch. Approximately 75 % of these latter sensory fibres displayed cardiac rhythm. In a separate study we also recorded 318 preganglionic neurones with axons in the right cardiac vagal branch of the rat. Respiratory-modulated preganglionic units were statistically less common than tonically firing units. Six preganglionic subtypes were categorised according to conduction velocity and respiratory discharge pattern. Myelinated B-fibre and unmyelinated C-fibre types were found to be equally prevalent and equally likely to be reflexly excited during the pulmonary chemoreflex and the peripheral arterial chemoreflexes. The electrophysiological analysis has shown how diverse the discharge patterns of the preganglionic neurones or interneurones are whose axons course in the right cardiac vagal branch of the rat. The results of these experiments demonstrate the usefulness of combining spike discrimination with multiple spike-triggered averaging to simultaneously record B and C centrifugal vagal efferents.

Vagal control of the cranial venae cavae of the rat heart.

The cranial venae cavae of the rat heart are composed of cardiac muscle. We tested whether the vagus nerve has an inotropic action on these blood vessels. Stimulation of right or left vagal fibres (n = 7 animals) produced a negative chronotropic and inotropic effect. Before stimulation the basal cardiac interval was 319 +/- 25 ms and the vena caval diastolic force was 1.82 +/- 0.29 mN and the systolic force was 3.28 +/- 0.39 mN. Ten second stimulation increased the cardiac interval to a maximum of 484 +/- 77 ms and reduced the systolic force significantly to 2.83 +/- 0.39 mN (two-tailed paired t test). The diastolic or baseline force was unaffected by vagal stimulation (1.85 +/- 0.29 mN). The vagal negative inotropic action took significantly longer to reach peak effect (9.5 +/- 1.0 s versus 3.2 +/- 0.9 s) and lasted longer than the chronotropic effect (20.4 +/- 2.1 s versus 10.25 +/- 1.2 s). The negative inotropic action was still observed in paced preparations and preparations with transient constant-rate tachyarrhythmias. Both the chronotropic and inotropic effects were abolished by atropine (10(-6) M) and mimicked by acetylcholine chloride (10 nM). In order to minimize an atrial contribution to the force production a more reduced preparation was used and ganglion clusters at the cavo-atrial junction were stimulated electrically (n = 4 animals). Similar negative inotropic and chronotropic effects sensitive to hexamethonium were seen. After hexamethonium administration, positive inotopic and chronotropic effects were uncovered and these were abolished by atenolol (0.1 mg %). Methylene Blue staining of the preparation at the end of the experiment showed the presence of ganglion cells at the sites of stimulation. Ganglion clusters were never seen on the venae cavae per se. The results of this investigation show that the vagus has a powerful action on the venae cavae resembling that on the atria and mediated by acetylcholine.

GABA-induced neurite outgrowth of cerebellar granule cells is mediated by GABA(A) receptor activation, calcium influx and CaMKII and erk1/2 pathways.

During neuronal development, GABAA-mediated responses are depolarizing and induce an increase in the intracellular calcium concentration. Since calcium oscillations can modulate neurite outgrowth, we explored the capability of GABA to induce changes in cerebellar granule cell morphology. We find that treatment with GABA (1-1000 microm) induces an increase in the intracellular calcium concentration through the activation of GABA(A) receptors and voltage-gated calcium channels of the L-subtype. Perforated patch-clamp recordings reveal that this depolarizing response is due to a chloride reversal potential close to - 35 mV. When cells are grown in depolarizing potassium chloride concentrations, a shift in reversal potential (Erev) for GABA is observed, and only 20% of the cells are depolarized by the neurotransmitter at day 5 in vitro. On the contrary, cells grown under resting conditions are depolarized after GABA application even at day 8. GABA increases the complexity of the dendritic arbors of cerebellar granule neurons via a calcium-dependent mechanism triggered by voltage-gated calcium channel activation. Specific blockers of calcium-calmodulin kinase II and mitogen-activated protein kinase kinase (KN93 and PD098059) implicate these kinases in the intracellular pathways involved in the neuritogenic effect of GABA. These data demonstrate that GABA exerts a stimulatory role on cerebellar granule cell neuritogenesis through calcium influx and activation of calcium-dependent kinases.