Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion-extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms

Adaptive Functions of the Corpus Striatum: The Past and Future of the R-Complex

The basal ganglia is emerging from the shadow cast by the most conspicuous clinical expression of its dysfunction: motor disorders.What is revealed is the nexus of a widely distributed system which functions in integrating action with cognition, motivation, and affect. Prominent among non-motor functions are striatal involvement in building up of sequences of behavior into meaningful, goal-directed patterns and repertoires and the selection of appropriate learned or innate sequences in concert with their possible predictive control. Further, striatum seems involved in declarative and strategic memory (involving intentional recollection and the management of retrieved memories, respectively). Findings from reptile experiments indicate striatal control over specific assemblies of innate units of behavior that involve autonomic modulation. Its involvement in the appropriate expression of species-typical action patterns in reptiles and primates provides an interesting vantage point from which to interpret its involvement in the assembly of units of behavior into specific adaptive behavioral patterns. For the current version with updated commentary, see https://notes.utk.edu/bio/greenberg.nsf/9e9a470d5230cdda852563ef0059fa56/89b6c6545b8412c185256a2c0060b638?OpenDocumen

Purkinje Cell Physiology in Health and Disease

Connections between neurons in the brain have physiological and morphological properties that can be altered over time to facilitate a behavioural acquisition process known as learning. I utilised behavioural tasks, electrophysiological, and tissue imaging techniques to study the physiological and morphological characteristics of Purkinje cells: the sole cortical output of the cerebellum. This dissertation consists of two parts. The first part explores experimental evidence for cerebellar dysfunction in cognitive related disease, like autism. The second part is focused on the fundamental aspects of Purkinje cell functioning with genetic mutations that lead to altered protein expression causing lasting dysfunctional synaptic functioning and consequentially impaired learning. I have performed experiments to study different types of input to the Purkinje cell to reveal synaptic changes that are ongoing and responsible for the aberrant cerebellum dependent learning. The work done here would not have been possible without the effort of many collaborators that helped reveal how genetic modifications can cause differential physiological and behavioural phenotypes