Models and Analysis of Vocal Emissions for Biomedical Applications

The MAVEBA Workshop proceedings, held on a biannual basis, collect the scientific papers presented both as oral and poster contributions, during the conference. The main subjects are: development of theoretical and mechanical models as an aid to the study of main phonatory dysfunctions, as well as the biomedical engineering methods for the analysis of voice signals and images, as a support to clinical diagnosis and classification of vocal pathologies

VOCAL BIOMARKERS OF CLINICAL DEPRESSION: WORKING TOWARDS AN INTEGRATED MODEL OF DEPRESSION AND SPEECH

Speech output has long been considered a sensitive marker of a person’s mental state. It has been previously examined as a possible biomarker for diagnosis and treatment response for certain mental health conditions, including clinical depression. To date, it has been difficult to draw robust conclusions from past results due to diversity in samples, speech material, investigated parameters, and analytical methods. Within this exploratory study of speech in clinically depressed individuals, articulatory and phonatory behaviours are examined in relation to psychomotor symptom profiles and overall symptom severity. A systematic review provided context from the existing body of knowledge on the effects of depression on speech, and provided context for experimental setup within this body of work. Examinations of vowel space, monophthong, and diphthong productions as well as a multivariate acoustic analysis of other speech parameters (e.g., F0 range, perturbation measures, composite measures, etc.) are undertaken with the goal of creating a working model of the effects of depression on speech. Initial results demonstrate that overall vowel space area was not different between depressed and healthy speakers, but on closer inspection, this was due to more specific deficits seen in depressed patients along the first formant (F1) axis. Speakers with depression were more likely to produce centralised vowels along F1, as compared to F2—and this was more pronounced for low-front vowels, which are more complex given the degree of tongue-jaw coupling required for production. This pattern was seen in both monophthong and diphthong productions. Other articulatory and phonatory measures were inspected in a factor analysis as well, suggesting additional vocal biomarkers for consideration in diagnosis and treatment assessment of depression—including aperiodicity measures (e.g., higher shimmer and jitter), changes in spectral slope and tilt, and additive noise measures such as increased harmonics-to-noise ratio. Intonation was also affected by diagnostic status, but only for specific speech tasks. These results suggest that laryngeal and articulatory control is reduced by depression. Findings support the clinical utility of combining Ellgring and Scherer’s (1996) psychomotor retardation and social-emotional hypotheses to explain the effects of depression on speech, which suggest observed changes are due to a combination of cognitive, psycho-physiological and motoric mechanisms. Ultimately, depressive speech is able to be modelled along a continuum of hypo- to hyper-speech, where depressed individuals are able to assess communicative situations, assess speech requirements, and then engage in the minimum amount of motoric output necessary to convey their message. As speakers fluctuate with depressive symptoms throughout the course of their disorder, they move along the hypo-hyper-speech continuum and their speech is impacted accordingly. Recommendations for future clinical investigations of the effects of depression on speech are also presented, including suggestions for recording and reporting standards. Results contribute towards cross-disciplinary research into speech analysis between the fields of psychiatry, computer science, and speech science

Study and characterisation of the prodromal motor phase of Parkinson’s Disease

There is sufficient evidence that a neurodegenerative process in Parkinson’s Disease (PD) starts many years before the clinical diagnosis. The progression of PD is generally slow and, because it is diagnosed based on established motor features, it is probable that subtle motor manifestations appear in the pre-diagnostic phase of PD. Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a condition known to be part of the prodromal phase of PD. The PREDICT-PD study is a population-based cohort which aims to identify individuals at risk of PD based on the presence and absence of risk factors. The first project of this thesis investigated the association between first presentation of motor symptoms (tremor, rigidity and balance difficulties) and subsequent PD in a large primary care dataset in East London, including almost 3 decades of clinical information from over a million individuals. People who went on to develop PD reported motor symptoms up to 10 years before PD diagnosis. Tremor had the highest association with future PD followed by balance difficulties and rigidity. The second project aimed to identify the range of motor features in the elderly population participating in the PREDICT-PD cohort study and document their rate of progression over time. People classified as having a higher risk of future PD (using the PREDICT-PD algorithm) were more likely to have early parkinsonian signs than the lower risk group. Six years later, they also showed a bigger motor decline compared with people in the lower risk group. The third project was focused on developing two new objective motor tools, the Distal Finger Tapping test and the Slow-Motion Analysis of Repetitive Tapping. Both tests were able to detect abnormal patterns of movement amongst people with early PD. Finally, a motor battery was created and implemented in a group of patients with iRBD. A higher proportion of patients with iRBD had early parkinsonian signs compared with controls. The motor battery was able to detect early patterns of motor dysfunction not captured by standardised clinical scales. The work presented in this thesis demonstrates that motor features start in the pre-diagnostic phase of PD and describes new motor signatures in the prodromal phase of PD

Application of MRI Connectivity in Stereotactic Functional Neurosurgery

This thesis examines potential applications of advanced MRI-connectivity studies in stereotactic functional neurosurgery. Several new analysis methodologies are employed to: (1) build predictive models of DBS surgery outcome; (2) refine the surgical target and (3) help build a better understanding of the pathogenesis of the treated conditions and the mechanism of action of DBS therapy. The experimental component is divided into three main parts focusing on the following pathologies: (1) Parkinson’s disease (PD), (2) tremor and (3) trigeminal autonomic cephalalgias (TAC). Section I: In the first experiment (chapter 3), resting state fMRI was used to find radiological biomarkers predictive of response to L-DOPA in 19 patients undergoing subthalamic nucleus (STN) DBS for PD. A greater improvement in UPDRS-III scores following L-DOPA administration was characterized by higher resting state functional connectivity (fcMRI) between the prefrontal cortex and the striatum (p=0.001) and lower fcMRI between the pallidum (p=0.001), subthalamic nucleus (p=0.003) and the paracentral lobule. In the second experiment (chapter 4), structural (diffusion) connectivity was used to map out the influence of the hyperdirect pathways on outcome and identify the therapeutic ‘sweet spots’ in twenty PD patients undergoing STN-DBS. Clusters corresponding to maximum improvement in symptoms were in the posterior, superior and lateral portion of the STN. Greater connectivity to the primary motor area, supplementary motor area and prefrontal cortex was predictive of higher improvement in tremor, bradykinesia and rigidity, and rigidity respectively. The third experiment (chapter 5) examined pyramidal tract (PT) activation in 20 PD patients with STN-DBS. Volume of tissue activation (VTA) around DBS contacts were modelled in relation to the PT. VTA/ PT overlap predicted EMG activation thresholds. Sections II: Pilot data suggest that probabilistic tractography techniques can be used to segment the ventrolateral (VL) and ventroposterior (VP) thalamus based on cortical and cerebellar connectivity in nine patients who underwent thalamic DBS for tremor (chapter 6). The thalamic area, best representing the ventrointermedialis nucleus (VIM), was connected to the contralateral dentate cerebellar nucleus. Streamlines corresponding to the dentato-rubro-thalamic tract (DRT) connected M1 to the contralateral dentate nucleus via the dentato-thalamic area. Good response was seen when the active contact’s VTA was in the thalamic area with the highest connectivity to the contralateral dentate nucleus. Section III: The efficacy and safety of DBS in the ventral tegmental area (VTa) in the treatment of chronic cluster headache (CH) and short lasting unilateral neuralgiform headache attacks (SUNA) were examined (chapters 7 and 8). The optimum stimulation site within the VTa that best controls symptoms was explored (chapter 9). The average responders’ deep brain stimulation activation volume lay on the trigemino-hypothalamic tract, connecting the trigeminal system and other nociceptive brainstem nuclei, with the hypothalamus, and the prefrontal and mesial temporal areas

Mental-State Estimation, 1987

Reports on the measurement and evaluation of the physiological and mental state of operators are presented

Neuroimaging of human motor control in real world scenarios: from lab to urban environment

The main goal of this research programme was to explore the neurophysiological correlates of human motor control in real-world scenarios and define mechanism-specific markers that could eventually be employed as targets of novel neurorehabilitation practice. As a result of recent developments in mobile technologies it is now possible to observe subjects' behaviour and monitor neurophysiological activity whilst they perform natural activities freely. Investigations in real-world scenarios would shed new light on mechanisms of human motor control previously not observed in laboratory settings and how they could be exploited to improve rehabilitative interventions for the neurologically impaired. This research programme was focussed on identifying cortical mechanisms involved in both upper- (i.e. reaching) and lower-limb (i.e. locomotion) motor control. Complementary results were obtained by the simultaneous recordings of kinematic, electromyographic and electrocorticographic signals. To study motor control of the upper-limb, a lab­based setup was developed, and the reaching movement of healthy young individuals was observed in both stable and unstable (i.e. external perturbation) situations. Robot-mediated force-field adaptation has the potential to be employed in rehabilitation practice to promote new skills learning and motor recovery. The muscular (i.e. intermuscular couplings) and neural (i.e. spontaneous oscillations and cortico­muscular couplings) indicators of the undergoing adaptation process were all symbolic of adaptive strategies employed during early stages of adaptation. The medial frontal, premotor and supplementary motor regions appeared to be the principal cortical regions promoting adaptive control and force modulation. To study locomotion control, a mobile setup was developed and daily life human activities (i.e. walking while conversing, walking while texting with a smartphone) were investigated outside the lab. Walking in hazardous environments or when simultaneously performing a secondary task has been demonstrated to be challenging for the neurologically impaired. Healthy young adults showed a reduced motor performance when walking in multitasking conditions, during which whole-brain and task-specific neural correlates were observed. Interestingly, the activity of the left posterior parietal cortex was predictive of the level of gait stability across individuals, suggesting a crucial role of this area in gait control and determination of subject specific motor capabilities. In summary, this research programme provided evidence on different cortical mechanisms operative during two specific scenarios for "real­world" motor behaviour in and outside the laboratory-setting in healthy subjects. The results suggested that identification of neuro-muscular indicators of specific motor control mechanisms could be exploited in future "real-world" rehabilitative practice