Pathophysiology Of Movement Disorders Research Articles

Impact of Parkinson's disease and dopaminergic medication on proprioceptive processing

Increasing evidence suggests that the pathophysiology of movement disorders in Parkinson's disease (PD) includes deficits in sensory processing and integration. However, the exact nature of these deficits and the ability of dopamine medication to correct them have not been thoroughly examined in previous studies. For instance, it remains unclear whether PD patients have globally impaired sensorimotor integration functions or selective deficiencies in processing proprioception. We evaluated the specific deficits of PD patients in sensorimotor integration and proprioceptive processing by testing their ability to perform three-dimensional (3D) reaching movements in four conditions in which the sensory signals defining target and hand positions (visual and/or proprioceptive) varied. Ten healthy subjects and 11 PD patients, ON dopamine medication and in the OFF state, were tested. PD patients in the OFF state showed a greater mean level of 3D errors relative to controls when the only available sensory information about target and hand position came from proprioception, but this difference did not reach significance. This indicates that deficient proprioception is not an early key feature of PD. Interestingly, the inaccuracies of a number of PD subjects further increased in the ON medicated state relative to healthy controls when reaching to proprioceptively-defined targets, and this between group difference was statistically significant. However, dopamine medication did not consistently degrade the reaching accuracy of PD patients, with both negative and positive effects on accuracy of reaching to proprioceptive-defined targets. Together, these findings indicate that dopamine replacement therapy not only did not normalize sensorimotor performance to the level of controls, but also induced deficits in the processing of proprioceptive information in some of the PD patients tested. Furthermore, the diversity of effects of medication on accuracy of reaching to proprioceptively-defined targets supports the idea that dysfunction of dopaminergic circuits within the basal ganglia is not primarily responsible for the proprioceptive processing deficits of PD patients.

White matter abnormalities in dystonia normalize after botulinum toxin treatment

The pathophysiology of dystonia is still poorly understood. We used diffusion tensor imaging to screen for white matter abnormalities in regions between the basal ganglia and the thalamus in cervical and hand dystonia patients. All patients exhibited an abnormal hemispheric asymmetry in a focal region between the pallidum and the thalamus. This asymmetry was absent 4 weeks after the same patients were treated with intramuscular botulinum toxin injections. These findings represent a new systems-level abnormality in dystonia, which may lead to new insights about the pathophysiology of movement disorders. More generally, these findings demonstrate central nervous system changes following peripheral reductions in muscle activity. This raises the possibility that we have observed activity-dependent white matter plasticity in the adult human brain.

Stimulation du cortex moteur, Parkinson et dystonie : que nous enseigne la stimulation magnétique transcrânienne? revue de la littérature

Over the last few years, deep brain stimulation techniques, with targets such as the subthalamic nucleus or the pallidum, have bee found to be beneficial in the treatment of Parkinson's disease and dystonia. Conversely, therapeutic strategies of cortical stimulation have not yet been validated in these diseases, although they are known to be associated with various cortical dysfunctions. Transcranial magnetic stimulation (TMS) is a valuable tool for non-invasive study of the role played by the motor cortex in the pathophysiology of movement disorders, in particular by assessing various cortical excitability determinants using single or paired pulse paradigms. In addition, repetitive TMS (rTMS) trains can be used to study the effects of transient activity changes of a targeted cortical area.Studies with TMS revealed significant motor cortex excitability changes, particularly regarding intracortical inhibitory pathways, both in Parkinson's disease and in dystonia, and these changes can be distinguished owing to the resting state or to the phases of movement preparation or execution. However, more specific correlation between electrophysiological features and clinical symptoms remains to be established. In addition, the stimulation of various cortical targets by rTMS protocols applied at low or high frequencies have induced some clear clinical effects.The TMS effects are and will remain applied in movement disorders to better understand the role played by the motor cortex, to assess various types of treatment and appraise the therapeutic potential of cortical stimulation.TMS provides evidence for motor cortex dysfunction in Parkinson's disease or dystonia. Moreover, rTMS results have opened new perspectives for therapeutic strategies of implanted cortical stimulation. By these both aspects, TMS techniques show their usefulness in the assessment of movement disorders.

Neuronal activity in the primate substantia nigra pars reticulata during the performance of simple and memory-guided elbow movements.

The basal ganglia participate in motor functions and are implicated in the pathophysiology of movement disorders. It has been shown in primates that the activity of many neurons in one of the basal ganglia output nuclei, the internal segment of the globus pallidus, changes with active or passive movements. The involvement of the second major output nucleus, the substantia nigra pars reticulata (SNr), in movement is less well established. In this study, the electrophysiologic activity of SNr neurons was studied in two awake Rhesus monkeys while the animals were examined and while they performed elbow movements in two different motor tasks (n = 261 cells). Responses to examination were uncommon and subtle. Twenty-one percent of neurons responded to the target step in a step tracking task, mostly with anticipatory responses, although some cells showed directional, movement-related activity. In a delayed-response task, 17% of cells showed anticipatory activity to an instruction cue preceding the target jump, 11% responded directly to the cue, and 11% showed long-lasting postcue activity. Movement-related responses were seen in 21% in this task. Reward responses occurred in 10% of neurons. Responses to more than one event were common. The results demonstrate that few neurons in the SNr respond directly to passive or active movements, but a large proportion shows responses that may be related to memory, attention, or movement preparation. While internal pallidal segment neurons may be preferentially concerned with controlling elemental movement parameters, neurons in the SNr may be more involved in higher motor functions or nonmotor aspects of behavior.

The Basal Ganglia and Involuntary Movements

The basal ganglia are organized to facilitate voluntary movements and to inhibit competing movements that might interfere with the desired movement. Dysfunction of these circuits can lead to movement disorders that are characterized by impaired voluntary movement, the presence of involuntary movements, or both. Current models of basal ganglia function and dysfunction have played an important role in advancing knowledge about the pathophysiology of movement disorders, but they have not contained elements sufficiently specific to allow for understanding the fundamental differences among different involuntary movements, including chorea, dystonia, and tics. A new model is presented here, building on existing models and data to encompass hypotheses of the fundamental pathophysiologic mechanisms underlying chorea, dystonia, and tics.

Sensorimotor integration in movement disorders.

Although current knowledge attributes movement disorders to a dysfunction of the basal ganglia-motor cortex circuits, abnormalities in the peripheral afferent inputs or in their central processing may interfere with motor program execution. We review the abnormalities of sensorimotor integration described in the various types of movement disorders. Several observations, including those of parkinsonian patients' excessive reliance on ongoing visual information during movement tasks, suggest that proprioception is defective in Parkinson's disease (PD). The disturbance of proprioceptive regulation, possibly related to the occurrence of abnormal muscle-stretch reflexes, might be important for generating hypometric or bradykinetic movements. Studies with somatosensory evoked potentials (SEPs), prepulse inhibition, and event-related potentials support the hypothesis of central abnormalities of sensorimotor integration in PD. In Huntington's disease (HD), changes in SEPs and long-latency stretch reflexes suggest that a defective gating of peripheral afferent input to the brain might impair sensorimotor integration in cortical motor areas, thus interfering with the processing of motor programs. Defective motor programming might contribute to some features of motor impairment in HD. Sensory symptoms are frequent in focal dystonia and sensory manipulation can modify the dystonic movements. In addition, specific sensory functions (kinaesthesia, spatial-temporal discrimination) can be impaired in patients with focal hand dystonia, thus leading to a "sensory overflow." Sensory input may be abnormal and trigger focal dystonia, or defective "gating" may cause an input-output mismatch in specific motor programs. Altogether, several observations strongly support the idea that sensorimotor integration is impaired in focal dystonia. Although elemental sensation is normal in patients with tics, tics can be associated with sensory phenomena. Some neurophysiological studies suggest that an altered "gating" mechanism also underlies the development of tics. This review underlines the importance of abnormal sensorimotor integration in the pathophysiology of movement disorders. Although the physiological mechanism remains unclear, the defect is of special clinical relevance in determining the development of focal dystonia.

Models of Basal Ganglia Function and Pathophysiology of Movement Disorders

Movement disorders are categorized as hypokinetic (Parkinson's disease) or hyperkinetic (Huntington's disease, hemiballism, or dystonia). Neuroscience research over the last several years, using data obtained in animal models for these disorders and data from patients undergoing stereotactic surgery, has greatly advanced the knowledge of the pathophysiologic basis of these diseases. This article offers a summary and critique of current models of the pathophysiology underlying hypokinetic and hyperkinetic diseases and a discussion of the implications of these models for neurosurgical procedures as treatment for these disorders.

Pathophysiology of movement disorders

Pathophysiology of movement disorders

Modeling the functional organization of the basal ganglia. A parallel distributed processing approach

Despite recent advances in the understanding of the pathophysiology of movement disorders, little is known about the precise function the basal ganglia play in the control of movement. We review an approach to studying the function of neural systems that is based on the use of a class of computer models known as parallel distributed processors (PDPs) and indicate its potential range of applications to the study of movement disorders. PDPs can be used to construct computational devices that take into account the anatomical and pharmacological properties of real neural systems. They can also provide computational-level insights that can lead to novel hypotheses concerning brain function. We discuss both these approaches and outline a scheme of the functional organization of the basal ganglia, which predicts some of the pathophysiological mechanisms that mediate movement disorders and which can be formally modeled on a computer.

The endogenous opioid system in neurological disorders of the basal ganglia

The endogenous opioid peptides have for some time been implicated in the regulation of motor behavior in animals. Recently, however, there is increased evidence to suggest a role for these peptides in the control of human motor functions as well as in the pathophysiology of abnormal movement disorders. Degeneration of opioid peptide-containing neurons in the basal ganglia has been demonstrated in Parkinson's disease and Huntington's chorea, but the clinical significance of these findings is largely unknown. On the other hand, there is evidence that excessive opioid activity may be important in the pathophysiology of some movement disorders such as tardive dyskinesia, progressive supra-nuclear palsy, and a subgroup of Tourette's patients. These findings indicate that diseases of the basal ganglia are possibly associated with alterations in opioid peptide activity, and that these alterations may be useful in designing experimental therapeutic strategies in these conditions.

The Pathophysiology of Movement Disorders

This review concentrated on the more recent findings of investigations into the functional anatomy and pathophysiology of movement disorders. Attempts were made to provide explanations for rigidity, bradykinesia, and tremor. What little is known of the pathophysiology of chorea, tics, and dystonia is discussed. Greater information is available to allow pathophysiologic classification of different types of myoclonus.