The clinical spectrum of sporadic and familial forms of frontotemporal dementia

The term frontotemporal dementia (FTD) describes a clinically, genetically and pathologically diverse group of neurodegenerative disorders. Symptoms of FTD can present in individuals in their twenties through to their nineties, but the mean age at onset is in the sixth decade. The most common presentation is with a change in personality and impaired social conduct (behavioural variant FTD). Less frequently patients present with language problems (primary progressive aphasia). Both of these groups of patients can develop motor features consistent with either motor neuron disease (usually the amyotrophic lateral sclerosis variant) or parkinsonism (most commonly a progressive supranuclear palsy or corticobasal syndrome). In about a third of cases FTD is familial, with mutations in the progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72 genes being the major causes. Mutations in a number of other genes including TANK-binding kinase 1 are rare causes of familial FTD. This review aims to clarify the often confusing terminology of FTD, and outline the various clinical features and diagnostic criteria of sporadic and familial FTD syndromes. It will also discuss the current major challenges in FTD research and clinical practice, and potential areas for future research. This article is protected by copyright. All rights reserved

Dysarthric speech analysis and automatic recognition using phase based representations

Dysarthria is a neurological speech impairment which usually results in the loss of motor speech control due to muscular atrophy and poor coordination of articulators. Dysarthric speech is more difficult to model with machine learning algorithms, due to inconsistencies in the acoustic signal and to limited amounts of training data. This study reports a new approach for the analysis and representation of dysarthric speech, and applies it to improve ASR performance. The Zeros of Z-Transform (ZZT) are investigated for dysarthric vowel segments. It shows evidence of a phase-based acoustic phenomenon that is responsible for the way the distribution of zero patterns relate to speech intelligibility. It is investigated whether such phase-based artefacts can be systematically exploited to understand their association with intelligibility. A metric based on the phase slope deviation (PSD) is introduced that are observed in the unwrapped phase spectrum of dysarthric vowel segments. The metric compares the differences between the slopes of dysarthric vowels and typical vowels. The PSD shows a strong and nearly linear correspondence with the intelligibility of the speaker, and it is shown to hold for two separate databases of dysarthric speakers. A systematic procedure for correcting the underlying phase deviations results in a significant improvement in ASR performance for speakers with severe and moderate dysarthria. In addition, information encoded in the phase component of the Fourier transform of dysarthric speech is exploited in the group delay spectrum. Its properties are found to represent disordered speech more effectively than the magnitude spectrum. Dysarthric ASR performance was significantly improved using phase-based cepstral features in comparison to the conventional MFCCs. A combined approach utilising the benefits of PSD corrections and phase-based features was found to surpass all the previous performance on the UASPEECH database of dysarthric speech

Effectiveness of intensive physiotherapy for gait improvement in stroke: systematic review

Introduction: Stroke is one of the leading causes of functional disability worldwide. Approximately 80% of post-stroke subjects have motor changes. Improvement of gait pattern is one of the main objectives of physiotherapists intervention in these cases. The real challenge in the recovery of gait after stroke is to understand how the remaining neural networks can be modified, to be able to provide response strategies that compensate for the function of the affected structures. There is evidence that intensive training, including physiotherapy, positively influences neuroplasticity, improving mobility, pattern and gait velocity in post-stroke recovery. Objectives: Review and analyze in a systematic way the experimental studies (RCT) that evaluate the effects of Intensive Physiotherapy on gait improvement in poststroke subjects. Methodology: Were only included all RCT performed in humans, without any specific age, that had a clinical diagnosis of stroke at any stage of evolution, with sensorimotor deficits and functional gait changes. The databases used were: Pubmed, PEDro (Physiotherapy Evidence Database) and CENTRAL (Cochrane Center Register of Controlled Trials). Results: After the application of the criteria, there were 4 final studies that were included in the systematic review. 3 of the studies obtained a score of 8 on the PEDro scale and 1 obtained a score of 4. The fact that there is clinical and methodological heterogeneity in the studies evaluated, supports the realization of the current systematic narrative review, without meta-analysis. Discussion: Although the results obtained in the 4 studies are promising, it is important to note that the significant improvements that have been found, should be carefully considered since pilot studies with small samples, such as these, are not designed to test differences between groups, in terms of the effectiveness of the intervention applied. Conclusion: Intensive Physiotherapy seems to be safe and applicable in post-stroke subjects and there are indications that it is effective in improving gait, namely speed, travelled distance and spatiotemporal parameters. However, there is a need to develop more RCTs with larger samples and that evaluate the longterm resultsN/

Changes in speech intelligibility and acoustic distinctiveness along a speech rate continuum in Parkinson’s disease

Asking a person to speak slowly is a common technique in speech therapy for people with Parkinson’s disease (PD). Slowed speaking rates are thought to bring about changes in speech production that make it easier for people with speech impairments associated with PD to be understood, but this is not always the case. Furthermore, research suggests that using faster speech does not necessarily lead to decreases in speech intelligibility for some people with PD. Most studies of rate modification in PD have only included one or two rate adjustments to investigate the relationship between speech rate, intelligibility, and acoustic aspects of speech production. The present study adds to this literature and expands it by eliciting a broader range of speech rates than has previously been studied in order to provide a comprehensive description of changes along such a continuum. Two groups of people with PD and documented speech changes participated: 22 receiving standard pharmaceutical intervention, and 12 who additionally had undergone deep brain stimulation surgery (DBS), a common surgical treatment for PD. DBS is often associated with further speech impairment, but it is unknown to what extent these individuals may benefit from speech rate adjustments. Younger and older healthy control groups were also included. All participants were asked to modify their speech rate along a seven-step continuum from very slow to very fast while reading words, sentences, and responding to prompts. Naïve listeners later heard these speech samples and were asked to either transcribe or rate what they heard. Results indicated different patterns of speech changes across groups, rates, and tasks. Sentence reading and conversational speech were rated as being more intelligible at slow rates, and less intelligible at fast rates. All modified rates were found to negatively impact speech sound identification during a novel carrier phrase task. Slower speech was overall associated with greater acoustic contrast and variability, lower intensity, and higher voice quality. Differences in acoustic speech adjustments across the groups and speech rates emerged, however, in particular for the DBS group. Findings pointed to a complex relationship between speech rate modifications, acoustic distinctiveness, and intelligibility

Effects of deep brain stimulation on speech in patients with Parkinson’s disease and dystonia

Disorders affecting the basal ganglia can have a severe effect on speech motor control. The effect can vary depending on the pathophysiology of the basal ganglia disease but in general terms it can be classified as hypokinetic or hyperkinetic dysarthria. Despite the role of basal ganglia on speech, there is a marked discrepancy between the effect of medical and surgical treatments on limb and speech motor control. This is compounded by the complex nature of speech and communication in general, and the lack of animal models of speech motor control. The emergence of deep brain stimulation of basal ganglia structures gives us the opportunity to record systematically the effects on speech and attempt some assumptions on the role of basal ganglia on speech motor control. The aim of the present work was to examine the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) and globus pallidus internus (GPi-DBS) for dystonia on speech motor control. A consecutive series of PD and dystonia patients who underwent DBS was evaluated. Patients were studied in a prospective longitudinal manner with both clinical assessment of their speech intelligibility and acoustical analysis of their speech. The role of pre-operative clinical factors and electrical parameters of stimulation, mainly electrode positioning and voltage amplitude was systematically examined. In addition, for selected patients, tongue movements were studied using electropalatography. Aerodynamic aspects of speech were also studied. The impact of speech therapy was assessed in a subgroup of patients. The clinical evaluation of speech intelligibility one and three years post STN-DBS in PD patients showed a deterioration of speech, partly related to medially placed electrodes and high amplitude of stimulation. Pre-operative predictive factors included low speech intelligibility before surgery and longer disease duration. Articulation rather than voice was most frequently affected with a distinct dysarthria type emerging, mainly hyperkinetic-dystonic, rather than hypokinetic. Traditionally effective therapy for PD dysarthria had little to no benefit following STN-DBS. Speech following GPi-DBS for dystonia did not significantly change after one year of stimulation. A subgroup of patients showed hypokinetic features, mainly reduced voice volume and fast rate of speech more typical of Parkinsonian speech. Speech changes in both STN-DBS and GPi-DBS were apparent after six months of stimulation. This progressive deterioration of speech and the critical role of the electrical parameters of stimulation suggest a long-term effect of electrical stimulation of basal ganglia on speech motor control

The utility of the auditory brainstem response in children with atypical saccadic eye movements

Full version unavailable due to 3rd party copyright restrictionsLesions in the brainstem result in widespread damage to a number of sensorimotor systems including oculomotor and auditory neural circuits. Although these systems are spatially separate and highly specialised, they are also co-located. This thesis, investigates whether lesions in the oculomotor system will also cause co-morbid dysfunction in the auditory pathways. Specifically, we investigated the usefulness of the Auditory Brainstem Response (ABR) in two oculomotor conditions: slow saccades in Gaucher disease (GD) and opsoclonus in Dancing Eye Syndrome (DES). We present four empirical studies. In our first study we systematically investigated the ABR in GD. We found that multimodal testing can better delineate underlying neurological deficits in neuronopathic GD (nGD) and distinguish between phenotypes. In the second study we examined the ABR's utility as a longitudinal, objective marker of disease burden and in a randomised clinical control trial. ABRs continued to deteriorate regardless of treatment. In our third study we assessed audiological function in DES. We found that at least 43% of DES patients have hyperacusis. We also found subtle abnormalities in the auditory brainstem, as shown by the ABR. Our final study explored the onset-offset response in the ABR and assessed its utility as a clinical marker. Overall, this thesis provides new evidence that auditory pathways are also affected in diseases which are traditionally assumed to be ‘oculomotor’ in nature. We believe that there is sufficient evidence to warrant the inclusion of audiological testing, such as the ABR, as part of the standard assessment of newly diagnosed GD patients and that they undergo these tests prior to commencing treatment. These tests may also have a wider application as longitudinal outcome measures for use in clinical trials or as markers of neurological burden in GD and we believe may be useful in other metabolic diseases; we found that current therapies for GD have low efficacy. Understanding the underlying neurological deficits in these debilitating illnesses can only help to improve treatments and the long-term outlook for these patients

Voice quality of children and young people with Down's Syndrome and its impact on listener judgement

Background: Voice quality in Down's syndrome (DS) is accepted as unusual, often perceived as harsh and whispery with lower pitch and altered nasal resonance. Less is known about the resulting impact, particularly in relation to how children and young people with DS are accepted by their peers. Method: This is a quantitative study of the voice quality of children and young people with DS compared to age-matched typically-developing (TD) controls. Expert raters use the Vocal Profile Analysis Scheme to perceptually rate voice, which is compared to instrumental analysis of fundamental frequency, perturbation measures and spectral tilt. The impact of typical and atypical voice quality is evaluated in a study of listener judgments of character, ability, age, gender and social desirability using a specially designed semantic-differential questionnaire completed by special-needs and mainstream education staff and TD peers based on audio-recordings. Results: Perceptually, a number of features, including lip, tongue and jaw settings, pharyngeal constriction and respiratory support were found to be atypical compared to controls, whilst other features, notably phonation type and nasality, echoed typical patterns but were more severe in presentation in the speakers with DS. Contrary to hypotheses only spectral tilt differed significantly in instrumental analysis. All groups of raters judged the speakers with DS significantly more negatively than controls across all questionnaire parameters. TD peers showed a strong preference for the company of TD children over those with DS. Conclusions: Perceptual differences are evident in the voices of children with DS, but these are not always supported by instrumental findings, perhaps indicating that the constellation of differences give rise to more negative perception. Close agreement between education staff groups suggests that children with DS are no more disadvantaged by the perception of teachers in mainstream than in special-schools; however particular difficulties are highlighted for the development of friendships with TD peers.sub_shsunpub352_ethesesunpu