Parkinson’s disease (PD) is a movement disorder traditionally thought to be caused by the degeneration of striatal dopaminergic neurons in the substantia nigra. One of the most devastating symptoms of PD that can decrease mobility and substantially impair quality of life is freezing of gait (FOG). Currently, the treatments for the motor symptoms of PD (e.g., levodopa, deep brain stimulation) are ineffective at managing FOG as the disease progresses. These treatments only target the cortical-striatal pathways of volitional movement that are dependent on dopamine, whereas FOG may be caused by the degeneration of other non-dopaminergic subcortical nuclei that are involved with posture and gait control (e.g., the pedunculopontine nucleus). A well-characterized behavior observed in PD that could contribute to FOG is a diminished ability to properly coordinate anticipatory postural adjustments (APAs) prior to the first step. In particular, diminished muscle activation leads to impaired limb mechanics and slower, less-coordinated gait initiation. Sensory cues have been demonstrated to improve gait initiation behaviors, possibly because they provide relevant information for movement to the motor cortex through cerebellar-thalamo-parietal pathways that remain intact during the disease process. However, sensory cues are not always reliable or effective in all contexts and are unable to directly modulate the force production of the user. Forms of mechanical stimuli can amplify force production during APAs by directly modulating force production and providing relevant timing and magnitude information through afferent sensory pathways. To date, no mechanical assistance that mimics the desired motion during an APA provided at the ankle joint in the form of modest ankle torques has been tested. The overall research objective of this dissertation work was to test the hypothesis that mechanical assistance provided at the ankle joint can be an effective paradigm for facilitating the diminished gait initiation behaviors in persons with PD and FOG symptoms. Biomechanical measurements and mechanical modeling techniques were used to explore the neuromechanical factors(e.g., cognitive, sensorimotor, biomechanical) that could enable this type of intervention or therapy.

1. The first research objective was to provide proof of concept that mechanical assistance provided at the ankle through a powered ankle-foot orthosis can shorten and amplify APAs compared to self-initiated stepping in healthy young adults.
2. The second research objective was to test the hypothesis that mechanical assistance provided at the ankle by a wearable powered ankle-foot orthosis can directly shorten and amplify gait initiation APAs compared to self-initiated and acoustic cued stepping in persons with PD and FOG.
3. The third research objective was to evaluate how cue-induced modulation of APAs in persons with PD and FOG vary based on whether the external cue is initiated exogenously or is self-triggered.
4. The fourth research objective of this dissertation was to simulate the behaviors observed during the early phase of an APA for gait initiation in persons with PD and FOG using mechanical modeling techniques.
5. Results from these studies may inform future interventions or therapies that can provide mechanical assistance at the ankle during gait initiation for persons with PD and FOG. Such interventions could increase mobility and promote independence, thereby improving quality of life and decreasing morbidity for these patients.