Motor control system in Parkinson’s disease: a modeling approach

Parkinson’s disease is a neurodegenerative disorder due to the death of the dopaminergic neurons of the substantia nigra of the basal ganglia. The process that leads to these neural alterations is still unknown. Parkinson’s disease affects most of all the motor sphere, with a wide array of impairment such as bradykinesia, akinesia, tremor, postural instability and singular phenomena such as freezing of gait. Moreover, in the last few years the fact that the degeneration in the basal ganglia circuitry induces not only motor but also cognitive alterations, not necessarily implicating dementia, and that dopamine loss induces also further implications due to dopamine-driven synaptic plasticity got more attention. At the present moment, no neuroprotective treatment is available, and even if dopamine-replacement therapies as well as electrical deep brain stimulation are able to improve the life conditions of the patients, they often present side effects on the long term, and cannot recover the neural loss, which instead continues to advance. In the present thesis both motor and cognitive aspects of Parkinson’s disease and basal ganglia circuitry were investigated, at first focusing on Parkinson’s disease sensory and balance issues by means of a new instrumented method based on inertial sensor to provide further information about postural control and postural strategies used to attain balance, then applying this newly developed approach to assess balance control in mild and severe patients, both ON and OFF levodopa replacement. Given the inability of levodopa to recover balance issues and the new physiological findings than underline the importance in Parkinson’s disease of non-dopaminergic neurotransmitters, it was therefore developed an original computational model focusing on acetylcholine, the most promising neurotransmitter according to physiology, and its role in synaptic plasticity. The rationale of this thesis is that a multidisciplinary approach could gain insight into Parkinson’s disease features still unresolved.

Neural correlates of disbalanced motor control in major depression

Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF).

Subcortical electrostimulation to identify network subserving motor control

Objectives: Recent anatomical-functional studies have transformed our understanding of cerebral motor control away from a hierarchical structure and toward parallel and interconnected specialized circuits. Subcortical electrical stimulation during awake surgery provides a unique opportunity to identify white matter tracts involved in motor control. For the first time, this study reports the findings on motor modulatory responses evoked by subcortical stimulation and investigates the cortico-subcortical connectivity of cerebral motor control. Experimental design: Twenty-one selected patients were operated while awake for frontal, insular, and parietal diffuse low-grade gliomas. Subcortical electrostimulation mapping was used to search for interference with voluntary movements. The corresponding stimulation sites were localized on brain schemas using the anterior and posterior commissures method. Principal observations: Subcortical negative motor responses were evoked in 20/21 patients, whereas acceleration of voluntary movements and positive motor responses were observed in three and five patients, respectively. The majority of the stimulation sites were detected rostral of the corticospinal tract near the vertical anterior-commissural line, and additional sites were seen in the frontal and parietal white matter. Conclusions: The diverse interferences with motor function resulting in inhibition and acceleration imply a modulatory influence of the detected fiber network. The subcortical stimulation sites were distributed veil-like, anterior to the primary motor fibers, suggesting descending pathways originating from premotor areas known for negative motor response characteristics. Further stimulation sites in the parietal white matter as well as in the anterior arm of the internal capsule indicate a large-scale fronto-parietal motor control network. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.

Pain and motor control of the lumbopelvic region: effect and possible mechanisms

Many authors report changes in the control of the trunk muscles in people with low back pain (LBP). Although there is considerable disagreement regarding the nature of these changes, we have consistently found differential effects on the deep intrinsic and superficial muscles of the lumbopelvic region. Two issues require consideration; first, the potential mechanisms for these changes in control, and secondly, the effect or outcome of changes in control for lumbopelvic function. Recent data indicate that experimentally induced pain may replicate some of the changes identified in people with LBP. While this does not exclude the possibility that changes in control of the trunk muscles may lead to pain, it does argue that, at least in some cases, pain may cause the changes in control. There are many possible mechanisms, including changes in excitability in the motor pathway, changes in the sensory system, and factors associated. with the attention demanding, stressful and fearful aspects of pain. A new hypothesis is presented regarding the outcome from differential effects of pain on the elements of the motor system. Taken together these data argue for strategies of prevention and rehabilitation of LBP (C) 2003 Elsevier Science Ltd. All rights reserved.

The effect of motor control exercise versus placebo in patients with chronic low back pain

Background: While one in ten Australians suffer from chronic low back pain this condition remains extremely difficult to treat. Many contemporary treatments are of unknown value. One potentially useful therapy is the use of motor control exercise. This therapy has a biologically plausible effect, is readily available in primary care and it is of modest cost. However, to date, the efficacy of motor control exercise has not been established. Methods: This paper describes the protocol for a clinical trial comparing the effects of motor control exercise versus placebo in the treatment of chronic non-specific low back pain. One hundred and fifty-four participants will be randomly allocated to receive an 8-week program of motor control exercise or placebo (detuned short wave and detuned ultrasound). Measures of outcomes will be obtained at follow-up appointments at 2, 6 and 12 months after randomisation. The primary outcomes are: pain, global perceived effect and patient-generated measure of disability at 2 months and recurrence at 12 months. Discussion: This trial will be the first placebo-controlled trial of motor control exercise. The results will inform best practice for treating chronic low back pain and prevent its occurrence.

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

Adaptation of motor control to training and disuse : contribution of muscle synergy analysis and movement variability

The well-known degrees of freedom problem originally introduced by Nikolai Bernstein (1967) results from the high abundance of degrees of freedom in the musculoskeletal system. Such abundance in motor control have two sides: i) because it is unlikely that the Central Nervous System controls each degree of freedom independently, the complexity of the control needs to be reduced, and ii) because there are many options to perform a movement, a repetition of a given movement is never the same. It leads to two main topics in motor control and biomechanics: motor coordination and motor variability. The present thesis aimed to understand how motor systems behave and adapt under specific conditions. This thesis comprises three studies that focused on three topics of major interest in the field of sports sciences and medicine: expertise, injury risk and fatigue. The first study (expertise) has focused on the muscle coordination topic to further investigate the effect of expertise on the muscle synergistic organization, which ultimately may represent the underlying neural strategies. Studies 2 (excessive medial knee displacement) and 3 (fatigue) both aimed to better understand its impact on the dynamic local stability. The main findings of the present thesis suggest: 1) there is a great robustness in muscle synergistic organization between swimmers at different levels of expertise (study 1, chapter II), which ultimately indicate that differences in muscle coordination is mainly explained by peripheral adaptations; 2) injury risk factors such as excessive medial knee displacement (study 2, chapter III) and fatigue (study 3, chapter IV) alter the dynamic local stability of the neuromuscular system towards a more unstable state. This change in dynamic local stability represents a loss of adaptability in the neuromuscular system reducing the flexibility to adapt to a perturbation.

Methods for objective and interpretative evaluation of function and motor control: gait in perturbed condition and in the aquatic therapy

Gait analysis allows to characterize motor function, highlighting deviations from normal motor behavior related to an underlying pathology. The widespread use of wearable inertial sensors has opened the way to the evaluation of ecological gait, and a variety of methodological approaches and algorithms have been proposed for the characterization of gait from inertial measures (e.g. for temporal parameters, motor stability and variability, specific pathological alterations). However, no comparative analysis of their performance (i.e. accuracy, repeatability) was available yet, in particular, analysing how this performance is affected by extrinsic (i.e. sensor location, computational approach, analysed variable, testing environmental constraints) and intrinsic (i.e. functional alterations resulting from pathology) factors. The aim of the present project was to comparatively analyze the influence of intrinsic and extrinsic factors on the performance of the numerous algorithms proposed in the literature for the quantification of specific characteristics (i.e. timing, variability/stability) and alterations (i.e. freezing) of gait. Considering extrinsic factors, the influence of sensor location, analyzed variable, and computational approach on the performance of a selection of gait segmentation algorithms from a literature review was analysed in different environmental conditions (e.g. solid ground, sand, in water). Moreover, the influence of altered environmental conditions (i.e. in water) was analyzed as referred to the minimum number of stride necessary to obtain reliable estimates of gait variability and stability metrics, integrating what already available in the literature for over ground gait in healthy subjects. Considering intrinsic factors, the influence of specific pathological conditions (i.e. Parkinson’s Disease) was analyzed as affecting the performance of segmentation algorithms, with and without freezing. Finally, the analysis of the performance of algorithms for the detection of gait freezing showed how results depend on the domain of implementation and IMU position.

Design and Implementation of Single phase 230V to Three Phase Inverter Based on the Embedded System STM-32 Applied to motor control

In the field of Power Electronics, several types of motor control systems have been developed using STM microcontroller and power boards. In both industrial power applications and domestic appliances, power electronic inverters are widely used. Inverters are used to control the torque, speed, and position of the rotor in AC motor drives. An inverter delivers constant-voltage and constant-frequency power in uninterruptible power sources. Because inverter power supplies have a high-power consumption and low transfer efficiency rate, a three-phase sine wave AC power supply was created using the embedded system STM32, which has low power consumption and efficient speed. It has the capacity of output frequency of 50 Hz and the RMS of line voltage. STM32 embedded based Inverter is a power supply that integrates, reduced, and optimized the power electronics application that require hardware system, software, and application solution, including power architecture, techniques, and tools, approaches capable of performance on devices and equipment. Power inverters are currently used and implemented in green energy power system with low energy system such as sensors or microcontroller to perform the operating function of motors and pumps. STM based power inverter is efficient, less cost and reliable. My thesis work was based on STM motor drives and control system which can be implemented in a gas analyser for operating the pumps and motors. It has been widely applied in various engineering sectors due to its ability to respond to adverse structural changes and improved structural reliability. The present research was designed to use STM Inverter board on low power MCU such as NUCLEO with some practical examples such as Blinking LED, and PWM. Then we have implemented a three phase Inverter model with Steval-IPM08B board, which converter single phase 230V AC input to three phase 380 V AC output, the output will be useful for operating the induction motor.

Effects of utterance length on lip kinematics in aphasia

Most existing models of language production and speech motor control do not explicitly address how language requirements affect speech motor functions, as these domains are usually treated as separate and independent from one another. This investigation compared lip movements during bilabial closure between five individuals with mild aphasia and five age and gender-matched control speakers when the linguistic characteristics of the stimuli were varied by increasing the number of syllables. Upper and lower lip movement data were collected for mono-, bi- and tri-syllabic nonword sequences using an AG 100 EMMA system. Each task was performed under both normal and fast rate conditions. Single articulator kinematic parameters (peak velocity, amplitude, duration,and cyclic spatio-temporal index) were measured to characterize lip movements. Results revealed that compared to control speakers, individuals with aphasia showed significantly longer movement duration and lower movement stability for longer items (bi- and tri-syllables). Moreover, utterance length affected the lip kinematics, in that the monosyllables had smaller peak velocities, smaller amplitudes and shorter durations compared to bi- and trisyllables, and movement stability was lowest for the trisyllables. In addition, the rate-induced changes (smaller amplitude and shorter duration with increased rate) were most prominent for the short items (i.e., monosyllables). These findings provide further support for the notion that linguistic changes have an impact on the characteristics of speech movements, and that individuals with aphasia are more affected by such changes than control speakers.

Acoustic analyses of diadochokinesis in fluent and stuttering children

OBJECTIVES: The purpose of the study was to acoustically compare the performance of children who do and do not stutter on diadochokinesis tasks in terms of syllable duration, syllable periods, and peak intensity. METHODS: In this case-control study, acoustical analyses were performed on 26 children who stutter and 20 aged-matched normally fluent children (both groups stratified into preschoolers and school-aged children) during a diadochokinesis task: the repetition of articulatory segments through a task testing the ability to alternate movements. Speech fluency was assessed using the Fluency Profile and the Stuttering Severity Instrument. RESULTS: The children who stutter and those who do not did not significantly differ in terms of the acoustic patterns they produced in the diadochokinesis tasks. Significant differences were demonstrated between age groups independent of speech fluency. Overall, the preschoolers performed poorer. These results indicate that the observed differences are related to speech-motor age development and not to stuttering itself. CONCLUSIONS: Acoustic studies demonstrate that speech segment durations are most variable, both within and between subjects, during childhood and then gradually decrease to adult levels by the age of eleven to thirteen years. One possible explanation for the results of the present study is that children who stutter presented higher coefficients of variation to exploit the motor equivalence to achieve accurate sound production (i.e., the absence of speech disruptions).

Relationship Between Occlusion and Lisping in Children With Cleft Lip and Palate

Introduction: The literature suggests that individuals with history of cleft lip and palate who present with midfacial growth deficiency are at higher risk of presenting lisping. The relationship between distortions during production of linguoalveolar fricative sounds and the severity of malocclusion, however, has not been established for the population with cleft. Objective: To study the association between lisping and dental arch relationship. Methodology: Speech samples and dental arch casts were obtained from 106 children with operated unilateral cleft lip and palate (UCLP) during the stage of mixed dentition and before orthodontic treatment. Videotaped productions of the phrase/u saci saiw sedu/were rated by speech-language pathologists for the identification of lisping during [s]. Dental arch casts were rated by orthodontists using the Goslon Yardstick and the Five-Year Index to establish dental arch relationship. Results: Multiple logistic regression showed no significant association between lisping and dento-occlusal index (p = .802) and age (p = .662). Substantial interjudge agreement during auditory-perceptual ratings was found (kappa = .63). Almost perfect agreement was found between orthodontists while establishing the dental arch relationship (kappa = .81). Discussion: This study failed to reveal an association between lisping and dental arch relationship in children with operated UCLP. Multiple variables may play a role in determining occurrence of lisping, warranting further investigation.

Kinematic analysis of jaw function in children following traumatic brain injury

Primary objective: To investigate jaw movements in children following traumatic brain injury (TBI) during speech using electromagnetic articulography (EMA). Methods and procedures: Jaw movements of two non-dysarthric children ( aged 12.75 and 13.08 years) who had sustained a TBI were recorded using the AG-100 EMA system (Carstens Medizineletronik) during word-initial consonant productions. Mean quantitative kinematic parameters and coefficient of variation ( variability) values were calculated and individually compared to the mean values obtained by a group of six control children ( mean age 12.57 years, SD 1.52). Main outcomes and results: The two children with TBI exhibited word-initial consonant jaw movement durations that were comparable to the control children, with sub-clinical reductions in speed being offset by reduced distances. Differences were observed between the two children in jaw kinematic variability, with one child exhibiting increased variability, while the other child demonstrated reduced or comparable variability compared to the control group. Conclusions: Possible sub-clinical impairments of jaw movement for speech were exhibited by two children who had sustained a TBI, providing insight into the consequences of TBI on speech motor control development.