Basal ganglia control of anticipatory postural adjustments: effects of Parkinson's disease and its treatments

Hall, Leanne Marie (2012). Basal ganglia control of anticipatory postural adjustments: effects of Parkinson's disease and its treatments PhD Thesis, School of Health and Rehabilitation Sciences, The University of Queensland.

       
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Author Hall, Leanne Marie
Thesis Title Basal ganglia control of anticipatory postural adjustments: effects of Parkinson's disease and its treatments
School, Centre or Institute School of Health and Rehabilitation Sciences
Institution The University of Queensland
Publication date 2012
Thesis type PhD Thesis
Supervisor Paul Hodges
Sandra Brauer
Total pages 272
Total colour pages 23
Total black and white pages 249
Language eng
Subjects 110904 Neurology and Neuromuscular Diseases
110903 Central Nervous System
110603 Motor Control
Formatted abstract Despite intensive investigation, basal ganglia function is poorly understood. Through complex connections with the thalamus and cortex, the basal ganglia influence planning, initiation and execution of movement, as well as higher-order executive functions and learning. Parkinson's disease (PD) is a basal ganglia disorder in which death of dopaminergic neurons in the substantia nigra leads to bradykinesia, tremor, rigidity, postural instability and neuropsychological impairments associated with memory and learning.

The mainstay of treatment for motor signs in PD is dopamine replacement therapy using levodopa, and more recently, deep brain stimulation (DBS) of the subthalamic nucleus. These interventions fail to ameliorate symptoms across all body systems (orofacial, limb and trunk) and movement types. For instance, levodopa and DBS improve bradykinesia, tremor and rigidity of the extremities, but fail to improve postural control of trunk or orofacial systems, and levodopa adversely affects quality of balance control.

Non-responsiveness of some symptoms to levodopa has led to two hypotheses. First, trunk, orofacial and limb systems are controlled by different mechanisms. Second, functions (postural vs. voluntary movement) are controlled by different mechanisms. However, as no studies have tested all three body systems with comparable protocols, this issue remains unresolved.

A second key issue in PD research is the incomplete consideration of the complexity of movement. Not all movements are controlled in the same way, nor with the same level of basal ganglia involvement. Instead different movement subtypes (e.g. voluntary movement, centrally-initiated postural adjustments, reactive postural adjustments) need to be studied separately. This thesis deals specifically with centrally-initiated anticipatory postural adjustments (APAs). Postural deficits are demonstrated by the ability to adapt and refine APAs to changes in environment/task properties. PD has been suggested to cause deficits in procedural (implicit) learning, which may underlie impairments in adaption of postural strategies. Implicit learning and the ability to change set are inextricably linked and lend themselves to investigation via analysis of centrally-initiated postural adjustments that accompany voluntary movement, but are controlled without conscious awareness.

This thesis aimed to advance understanding of the contribution of the basal ganglia to motor control and motor learning through investigation of the effects of PD, levodopa and DBS on APAs in three different body systems: the trunk, upper limb and orofacial systems.

Study 1 aimed to develop a new protocol to investigate the contribution of the trunk, limb and jaw to APAs in a similar manner, and provide a means to examine changes in postural set and implicit learning. A rapid lower limb flexion task was validated in a young healthy population and provided normative data from which studies of people with PD and age-matched controls could be compared. Each body system was confirmed to participate in APAs.

High velocity voluntary movements necessitate greater postural preparation than slower movements. Impaired preparation is cited as a cause of postural instability in PD. Study 2 investigated the relationship between limb acceleration and APA amplitude and duration in people with PD ON and OFF levodopa, and control participants. The results showed APA parameters in PD are appropriate for the speed at which movement is performed and are unaffected by levodopa. Each body system responded in the same manner.

Investigations of reactive postural control in PD have revealed impaired adaptation to environmental/task changes. Examination of procedural learning using simple voluntary upper limb reaction time tasks also concludes that dopamine deficiency results in learning deficits. Studies of adaptation of APAs to changes in support, and the ability to learn/refine the motor task with practice, are lacking. Studies 3-5 investigated these phenomena in people with PD treated pharmacologically (Study 3) and with DBS (Study 4 and 5). Studies 3 and 4 showed that people with PD, regardless of treatment, immediately adapt the postural strategy to novel and familiar changes in postural support. A controversial finding, replicated in the medication-only condition in Study 5, was that levodopa compromised the ability to refine APAs with practice (Study 3). In contrast, DBS restored the ability to refine the postural strategy (Study 5). These observations can be interpreted three ways. First, implicit learning may be negatively influenced by excess dopamine (levodopa) and suppression of basal ganglia output by DBS may overcome the negative impact of excess dopamine. Second, activation of non-dopaminergic pathways by DBS may restore learning. Third, DBS may mimic/restore phasic (as opposed to tonic) dopamine function, which is essential for learning.

These five studies provide insight into the role of the basal ganglia in preparation for movement and the implicit learning required for adaptation to changes in environmental conditions. APAs,although prolonged and reduced in amplitude, are appropriate for parkinsonian movement. This was consistent across the 3 body systems, supporting the hypothesis that body systems are controlled similarly. Implicit learning is also intact, but impaired by the gold-standard treatment for PD. These results provide a basis for research into PD interventions and other areas of motor control.
Keyword Parkinson's disease
Dopamine
Basal ganglia
Postural control
Motor control

 
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Created: Fri, 10 Aug 2012, 08:35:53 EST by Leanne Hall on behalf of Scholarly Publishing and Digitisation Service