Optimal set of EEG features for emotional state classification and trajectory visualization in Parkinson's disease

In addition to classic motor signs and symptoms, individuals with Parkinson's disease (PD) are characterized by emotional deficits. Ongoing brain activity can be recorded by electroencephalograph (EEG) to discover the links between emotional states and brain activity. This study utilized machine-learning algorithms to categorize emotional states in PD patients compared with healthy controls (HC) using EEG. Twenty non-demented PD patients and 20 healthy age-, gender-, and education level-matched controls viewed happiness, sadness, fear, anger, surprise, and disgust emotional stimuli while fourteen-channel EEG was being recorded. Multimodal stimulus (combination of audio and visual) was used to evoke the emotions. To classify the EEG-based emotional states and visualize the changes of emotional states over time, this paper compares four kinds of EEG features for emotional state classification and proposes an approach to track the trajectory of emotion changes with manifold learning. From the experimental results using our EEG data set, we found that (a) bispectrum feature is superior to other three kinds of features, namely power spectrum, wavelet packet and nonlinear dynamical analysis; (b) higher frequency bands (alpha, beta and gamma) play a more important role in emotion activities than lower frequency bands (delta and theta) in both groups and; (c) the trajectory of emotion changes can be visualized by reducing subject-independent features with manifold learning. This provides a promising way of implementing visualization of patient's emotional state in real time and leads to a practical system for noninvasive assessment of the emotional impairments associated with neurological disorders

'Staying safe' – A narrative review of falls prevention in people with Parkinson’s -'PDSAFE'

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.Background: Parkinson's disease demonstrates a spectrum of motor and non-motor symptoms. Falling is common and disabling. Current medical management shows minimal impact to reduce falls, or fall related risk factors such as deficits in gait, strength and postural instability. Despite evidence supporting rehabilitation in reducing fall risk factors, the most appropriate intervention to reduce overall fall rate remains inconclusive. This paper aims to 1) synthesise current evidence and conceptual models of falls rehabilitation in Parkinson's in a narrative review; and based on this evidence 2) introduce the treatment protocol used in the falls prevention, multi-centre clinical trial 'PDSAFE'. Method: Search of four bibliographic databases using the terms ‘Parkinson*’ and ‘Fall*’ combined with each of the following; ‘Rehab*, Balanc*, Strength*, Strateg*and Exercis*' and a framework for narrative review was followed. 3557 papers were identified, 416 were selected for review. The majority report the impact of rehabilitation on isolated fall risk factors. Twelve directly measure the impact on overall fall rate. Discussion: Results were used to construct a narrative review with conceptual discussion based on the 'International Classification of Functioning’, leading to presentation of the 'PDSAFE' intervention protocol. Conclusion: Evidence suggests training single, fall risk factors may not affect overall fall rate. Combining with behavioural and strategy training in a functional, personalised multi-dimensional model, addressing all components of the ‘International Classification of Functioning’ is likely to provide a greater influence on falls reduction. 'PDSAFE' is a multi-dimensional, physiotherapist delivered, individually tailored, progressive, home-based programme. It is designed with a strong evidence based approach and illustrates a model for the clinical delivery of the conceptual theory discussed.This project was funded by the National Institute for Health Research Health Technologies Assessment programme (project number 10/57/21). VG is supported by the National Institute of Health Research Collaboration for Applied Health Research and Care South West Peninsula.

Does practice of multi-directional stepping with auditory stimulation improve movement performance in patients with Parkinson\u27s disease

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder causing many physical limitations. Rhythmic auditory stimulation (RAS) influences motor complications not alleviated by medicine and has been used to modify straight line walking in this population. However, motor complications are exacerbated during more complex movements including those involving direction changes. Thus immediate RAS effects on direction switch duration (DSD) and other kinematic measures during a multi-directional step task were investigated in PD patients. Long term RAS application was also explored by evaluating functional gait and balance and kinematic step measures before and after 6 weeks of multi-directional stepping either with (Cue, C group) or without (No cue, NC group) RAS use. Evaluations were also administered 1, 4 and 8 weeks after training termination. Kinematic measures were collected during stepping without, then with RAS for the C group and without RAS for the NC group. Step testing/training was performed at slow, normal and fast speeds in forward, back and side directions. Participants with PD switched step direction during the stepping task faster with RAS use before training. Like straight line walking RAS application influenced the more complex task of direction switching and counteracted the well-known bradykinesia in PD. After training both groups improved their functional gait and balance measures and maintained balance improvements for at least 8 weeks. Only the C group retained gait improvements for at least 8 weeks after training termination. Adding RAS resulted in functional benefits not observed in training without it. Kinematic measures compared before and after step training clarified the underlying contributors to functional performances. Both groups reduced the variability of DSD. The C group participants maintained this alteration longer. DSD reduction also occurred after training and was retained for at least 8 weeks for this group. These outcomes further support the advantages of adding RAS to training regiments for those with PD. The current results indicate that RAS effects are not limited to simple activities like straight line walking. Moreover, RAS can be used for improving and maintaining improvements longer in activities involving various forms of transition which present most difficulties for those with PD

The Influence of Dopamine Replacement on Movement Impairments During Bimanual Coordination in Parkinson’s Disease (PD)

The purpose of the current thesis was to investigate the influence of dopamine replacement on performance during bimanual coordination in individuals with Parkinson’s disease (PD) There has been conflicting research on the cause of movement impairments such as coordination deficits, slowed switching and upper limb freezing that occur during coordinated movements It is unclear whether decreased function of the dopaminergic system after withdrawal from dopamine replacement is responsible for these deficits Healthy age-matched control participants were compared to PD participants in two experiments to determine the movement impairments that occurred during three-dimensional wrist flexion-extension bimanual coordination as a result of PD. In addition, individuals with PD were compared without (‘off’) and with (‘on’) dopamine replacement in both experiments to determine whether modulation of the dopaminergic system influenced coordinated movements. In Experiment 1, continuous bimanual coordination was performed in m-phase (simultaneous wrist flexion and extension) and anti-phase (flexion of one wrist while extending other wrist) with movements externally paced with increasing across seven cycle frequencies (0.75 to 2 Hz). Visual feedback was also manipulated in one of three sensory conditions no vision, normal vision or augmented vision. Visual feedback, phase and cycle frequency manipulation was performed to determine whether other deficits (e.g. sensory and/or attentional deficits) may influence coordinated movements Despite reduced amplitude of movements in both limbs of individuals with PD (PD ‘off’), coordination deficits were not observed in PD compared to healthy control participants. In addition, there was an increased occurrence of upper limb freezing (ULF) when cycle frequency demand was greater Dopamine replacement did increase the amplitude of movements in individuals with PD but did not influence coordination performance or the occurrence of ULF. In Experiment 2, coordinated movements were initiated in either m-phase or antiphase and participants were required to voluntarily switch to the other phase pattern when an auditory cue was presented Trials were performed at one of two cycle frequencies (1 or 2 Hz) and one of two sensory conditions (no vision or normal vision) to determine whether other deficits (e.g. sensory and/or attentional deficits) may influence coordinated movement. In addition, a separate block of trials were performed in anti-phase coordination with an auditory cue that did not require a switch Non-switching trials were included to investigate whether the presence of a distracting cue could evoke ULF comparable to when switching between movements was required PD ‘off’ participants demonstrated slower switching, more delayed responses and deficits in coordination performance when compared to healthy control participants. The increased demand of cycle frequency particularly when initiating anti-phase coordination, after voluntary switching and with the presence of the auditory cue without switching contributed to a large occurrence of ULF in individuals with PD. Dopamine replacement improved the ability to switch between phase patterns but had no overall influence on coordination performance or the occurrence of ULF. Overall, the results of the current thesis demonstrated that dopamine replacement can improve motor symptoms during coordinated movements (e g hypometna and bradykinesia) but does not contribute to coordination performance or ULF in individuals with PD. As a consequence, it was concluded that coordination deficits and ULF are not caused by the dysfunctional dopaminergic system but rather associated to secondary impairment caused by PD. The movement impairments caused by secondary dysfunction of PD were proposed to be associated with increased attentional demands and possible executive dysfunction related to fronto-stnatal pathways that cannot be modulated by dopamine replacement. Thus, treatment of complex movement impairments such as coordination deficits and ULF may benefit from rehabilitation or non-dopamine therapies that focus on the global dysfunction caused by PD

INFLUENCE OF PLANNING RESOURCES ON GAIT CONTROL IN PARKINSON’S DISEASE

Movement disturbances in individuals with Parkinson’s disease (PD) have been associated with difficulties to plan complex actions. Performance of simple and complex actions overloads resources for individuals with Parkinson’s disease (PD). However, it is unclear if central resources required to plan gait adjustments while walking exacerbate gait disturbances of patients with PD. More specifically, it is unclear how gait impairments, sensory processing, and the dopaminergic system influence the load on processing resources (e.g. cognitive load) during the planning of step modifications. In order to investigate the relative influence of these factors on cognitive load and its impact on gait control, three experiments were conducted that utilized a naturalistic gait task, which challenged planning resources during obstacle avoidance. While the tasks were being performed, dual task interference on gait, and dual task performance were assessed in order to estimate participants’ cognitive load during these tasks. Gait control during obstacle approach and crossing were also evaluated to observe dual task interference on steps known to demand greater planning. In experiment 1 (chapter 2), the influence of gait impairments on planning resources was investigated. The results of this study demonstrated that the planning of gait adaptations in participants with freezing of gait (PD-FOG) resulted in a greater increase in cognitive load, relative to participants with more preserved gait PD-nonFOG (same disease severity without severe gait impairments). The influence of sensory processing on movement planning was investigated in experiment 2 (chapter 3). The results of this study revealed that removal of visual feedback of self-motion affected gait control when the planning of gait adjustments was necessary for successful crossing. In addition, PD patients prioritized walking over the secondary task when visual feedback was reduced, in order to compensate for impaired proprioceptive processing. Lastly, experiment 3 investigated the influence of the dopaminergic system on gait adjustments. The results of this study revealed that dopaminergic replacement partially decreased the effect of cognitive load on gait and drastically improved gait velocity as participants approached obstacles. This study also demonstrates that the cognitive load and the dopaminergic impairments in PD, did not force patients to rely more than healthy participants, on visual information from obstacle as to correct step adjustments. In sum, the current thesis suggests that increases in cognitive load during the planning of gait adaptations causes gait impairments, in individuals with PD. These increases in cognitive load appear to be associated with impaired sensorimotor processing during gait. Dopaminergic activity modulated sensorimotor processing during movement planning and partially the cognitive load caused by movement planning. Finally, the results of these studies suggest that the complexity to plan gait adjustments, while walking, overtax processing resources of individuals with PD causing some observable gait impairments

Rat Model of Pre-Motor Parkinson\u27s Disease: Behavioral and MRI Characterization.

Background: Parkinson\u27s disease (PD) is a chronic, progressive, neurodegenerative disorder with currently no known cure. PD has a significant impact on quality of life of the patients, as well as, the caregivers and family members. It is the second most common cause of chronic neurological disability in US and Europe. According to National Parkinson\u27s Foundation, there are almost 1 million patients in the Unites States and 50,000 to 60,000 new cases of PD are diagnosed each year. The total number of cases of PD is predicted to double by 2030. The annual cost associated with this disease is estimated to be $10.8 billion in the United States, including the cost of treatment and the cost of the disability. Although it is primarily thought of as a movement-disorder and is clinically diagnosed based on motor symptoms, non-motor symptoms such as cognitive and emotional deficits are thought to precede the clinical diagnosis by almost 20 years. By the time of clinical diagnosis, there is 80% loss in the dopamine content in the striatum and 50% degeneration of the substantia nigra dopamine cells. The research presented in this thesis was an attempt to develop an animal model of PD in its pre-motor stages. Such a model would allow us to develop pre-clinical markers for PD, and facilitate the development and testing of potential treatment strategies for the non-motor symptoms of the disorder. Specific Aims: There were five specific aims for this research: * The first specific aim dealt with development of a rat model of PD with slow, progressive onset of motor deficits, determination of timeline for future studies, and quantification the dopamine depletion in this model at a pre-motor stage. * The second and the third specific aims focused on testing for emotional (aversion) deficits and cognitive (executive functioning) deficits in this rat model at the 3 week timepoint determined during specific aim 1. * The fourth specific aim was to determine the brain network changes associated with the behavioral changes observed our rat model using resting state connectivity as a measure. * The fifth and the final specific aim was to test sodium butyrate, a drug from the histone deacetylase inhibitor family, as a potential treatment option for cognitive deficits in PD. Results: The 6-hydroxy dopamine based stepwise striatal lesion model of pre-motor PD, developed during this research, exhibits delayed onset of Parkinsonian gait like symptoms by week 4 after the lesions. At 3 weeks post lesion (3WKPD), the rats exhibit 27% reduction in striatal dopamine and 23%reduction in substantia nigra dopamine cells, with lack of any apparent motor deficits. The 3WKPD rats also exhibited changes in aversion. The fMRI study with the aversive scent pointed towards possible amygdala dysfunction sub-serving the aversion deficits. The executive function deficits tested using a rat analog of the Wisconsin card sorting test, divulged an extra-dimensional set shifting deficit in the 3WKPD rats similar to those reported in PD patients. The resting state connectivity study indicated significant changes in the 3WKPD rats compared to age matched controls. We observed increased overall connectivity of the motor cortex and increased CPu connectivity with prefrontal cortex, cingulate cortex, and hypothalamus in the 3WKPD rats compared to the controls. These observations parallel the observations in unmedicated early-stage PD patients. We also observed negative correlation between amygdala and prefrontal cortex as reported in humans. This negative correlation was lost in 3WKPD rats. Sodium butyrate treatment, tested in the cognitive deficit study, was able to ameliorate the extra-dimensional set shifting deficit observed in this model. This treatment also improved the attentional set formation. Conclusion: Taken together, our observations indicate that, the model of pre-motor stage PD developed during this research is a very high face validity rat model of late Braak stage 2 or early Braak stage 3 PD. Sodium butyrate was able to alleviate the cognitive deficits observed in our rat model. Hence, along with the prior reports of anti-depressant and neuroprotective effects of this drug, our results point towards a possible treatment strategy for the non-motor deficits of PD

Dynamic control of posture across locomotor tasks

Successful locomotion depends on postural control to establish and maintain appropriate postural orientation of body segments relative to one another and to the environment, and to ensure dynamic stability of the moving body. This paper provides a framework for considering dynamic postural control, highlighting the importance of coordination, consistency, and challenges to postural control posed by various locomotor tasks such as turning and backward walking. The impacts of aging and various movement disorders on postural control are discussed broadly in an effort to provide a general overview of the field and recommendations for assessment of dynamic postural control across different populations in both clinical and research settings. Suggestions for future research on dynamic postural control during locomotion are also provided and include discussion of opportunities afforded by new and developing technologies, the need for long-term monitoring of locomotor performance in everyday activities, gaps in our knowledge of how targeted intervention approaches modify dynamic postural control, and the relative paucity of literature regarding dynamic postural control in movement disorder populations other than Parkinson disease