Basal ganglia disease

Basal ganglia disease is a group of physical problems that occur when the group of nuclei in the brain known as the basal ganglia fail to properly suppress unwanted movements or to properly prime upper motor neuron circuits to initiate motor function. Research indicates that increased output of the basal ganglia inhibits thalamocortical projection neurons. Proper activation or deactivation of these neurons is an integral component for proper movement. If something causes too much basal ganglia output, then the Ventral Anterior (VA) and Ventral Lateral (VL) thalamocortical projection neurons become too inhibited and one cannot initiate voluntary movement. These disorders are known as hypokinetic disorders. However, a disorder leading to abnormally low output of the basal ganglia leads to relatively no inhibition, and thus excitation, of the thalamocortical projection neurons (VA and VL) which synapse onto the cortex. This situation leads to an inability to suppress unwanted movements. These disorders are known as hyperkinetic disorders. Currently, reasons for abnormal increases or decreases of basal ganglia output are poorly understood. One possible factor could be the natural accumulation of iron in the basal ganglia, causing neurodegeneration due to its involvement in toxic, free-radical reactions. Though motor disorders are the most common associated with the basal ganglia, recent research shows that basal ganglia disorders can lead to other dysfunctions such as obsessive compulsive disorder (OCD) and Tourette syndrome. Basal ganglia disease is a group of physical problems that occur when the group of nuclei in the brain known as the basal ganglia fail to properly suppress unwanted movements or to properly prime upper motor neuron circuits to initiate motor function. Research indicates that increased output of the basal ganglia inhibits thalamocortical projection neurons. Proper activation or deactivation of these neurons is an integral component for proper movement. If something causes too much basal ganglia output, then the Ventral Anterior (VA) and Ventral Lateral (VL) thalamocortical projection neurons become too inhibited and one cannot initiate voluntary movement. These disorders are known as hypokinetic disorders. However, a disorder leading to abnormally low output of the basal ganglia leads to relatively no inhibition, and thus excitation, of the thalamocortical projection neurons (VA and VL) which synapse onto the cortex. This situation leads to an inability to suppress unwanted movements. These disorders are known as hyperkinetic disorders. Currently, reasons for abnormal increases or decreases of basal ganglia output are poorly understood. One possible factor could be the natural accumulation of iron in the basal ganglia, causing neurodegeneration due to its involvement in toxic, free-radical reactions. Though motor disorders are the most common associated with the basal ganglia, recent research shows that basal ganglia disorders can lead to other dysfunctions such as obsessive compulsive disorder (OCD) and Tourette syndrome. The basal ganglia is a collective group of structures in the brain. These include the striatum, (composed of the putamen and caudate nucleus), globus pallidus, substantia nigra, and the subthalamic nucleus. Along with other structures, the basal ganglia are part of a circuit that is integral to voluntary motor function. It was once believed that the primary function of the basal ganglia was to integrate projections from the cerebral cortex, and project information via the thalamus to the motor cortex. New research shows that the basal ganglia can be modeled as a group of components of parallel, reentrant cortico-subcortical circuits, which originate in cortical areas, traverse the basal ganglia and terminate in specific areas in the frontal lobe. These areas are thought to control not only motor function but also oculomotor, prefrontal, associative, and limbic areas. Understanding these circuits has led to breakthroughs in understanding the disorders of the basal ganglia. Of all the circuits, the motor circuit is the most studied due its importance to motor disorders. The direct pathway of the motor circuit is one in which projections from the cortex travel to the putamen directly to the internal segment of the globus pallidus (GPi also known as GP-Medial) or the substantia nigra, pars reticulata (SNr) and are then directed toward the ventral anterior nucleus (VA), and the ventral lateral nucleus of the thalamus (VL) and brainstem.Through this pathway the basal ganglia is able to initiate voluntary movements by disinhibiting thalamic neurons that drive upper motor neurons. This process is regulated by dopamine secreted by the striatum onto the D1 dopamine receptor on the SNc. Dopamine excites striatal neurons in the direct pathway. Proper striatal dopamine release is integral in the suppression of the basal ganglia output, which is needed for increased activity of the thalamic neurons. This activity in thalamic nuclei is an integral component of voluntary movement. The indirect pathway of the motor circuit is thought to project from the cortex, to the putamen, and to the thalamus and brainstem indirectly by passing through the external segment of the globus pallidus (GPe) then the subthalamic nucleus (STN) before looping back to the internal segment of the globus pallidus (GPi). The indirect pathway is responsible for the termination of movement. The indirect pathway inhibits unwanted movements by simultaneous increase in excitatory input to other GPi and SNr neurons. Similar to the direct pathway, the indirect pathway is regulated by striatal dopamine. D2 dopamine receptors inhibit transmission via the indirect pathway. D2 receptors inhibit striatal neurons in the indirect, inhibitory pathway. This inhibitory effect of dopamine on the indirect pathway serves the same function as its excitatory effects in the direct pathway in that it reduces basal ganglia output, leading to the disinhibition of motor neurons. Hypokinetic disorders are movement disorders that are described as having reduced motor function. This is generally attributed to higher than normal basal ganglia output causing inhibition of thalamocortical motor neurons. The muscle rigidity, tremor at rest, and slowness in initiation and execution of movement that are the cardinal motor symptoms of Parkinson's disease are attributed to a reduction in dopaminergic activity in the basal ganglia motor areas, particularly the putamen, due to gradually reduced innervation from the pars compacta of substantia nigra. Other motor deficits and common non-motor features of Parkinson's such as autonomic dysfunction, cognitive impairment, and gait/balance difficulties, are thought to result from widespread progressive pathological changes commencing in the lower brain stem and ascending to the midbrain, amygdala, thalamus and ultimately the cerebral cortex.