Төменгі мидағы белгісіз аймақ: Zona incerta

Region of gray matter cells in the subthalamus below the thalamus

The zona incerta (ZI) is a horizontally elongated region of gray matter in the subthalamus below the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord. Its function is unknown, though several potential functions related to "limbic–motor integration" have been proposed, such as controlling visceral activity and pain; gating sensory input and synchronizing cortical and subcortical brain rhythms. Its dysfunction may play a role in central pain syndrome. It has also been identified as a promising deep brain stimulation therapy target for treating Parkinson's disease. Its existence was first described by Auguste Forel in 1877 as a "region of which nothing certain can be said". A hundred and thirty years later in 2007, Nadia Urbain and Martin Deschênes of Université Laval noted that the "zona incerta is among the least studied regions of the brain; its name does not even appear in the index of many textbooks."

Zona incerta controls such activities as water and food intake, sexuality and cardiovascular activity. This control is related to its effects upon the nearby posterior hypothalamus with which it shares similar connections and neurochemically defined cell types. The zona incerta receives pain input through the spinothalamic tract and this has been shown to control the activity of the pain transmission pathway in the posterior thalamus. Electrical or chemical stimulation of the zona incerta creates limbic related movements, such as those associated with defense orientation and copulation.

At rest sensory input to the higher sensory areas of the cerebral cortex is gated through the thalamus. It has moreover been proposed that the zona incerta provides a top down disinhibitory mechanism of this gating when there is sensory motor activity such as the tactile use of whiskers. This has also been linked to sensory gating changes between sleep and waking. In this occurs a zona incerta mediated inhibition of thalamic nuclei such the somatosensory posterior medial thalamus. This is most strong when cholinergic input to the zona incerta is reduced as during slow wave sleep and during anesthesia. The consequence of this has been explained upon information processing: <blockquote> As a result, posterior medial thalamus neurons fail to respond to ascending sensory inputs, and function primarily in "higher order" mode, concerned with relaying trans cortical information. By contrast, increased cholinergic activity during wakefulness and enhanced vigilance suppresses zona incerta mediated inhibition, thereby ungating posterior thalamus responses to ascending inputs.

The GABAergic input received from the cerebral cortex has been suggested to synchronize thalamocortical and brainstem rhythms by providing a link between basal ganglia output and the cerebello thalamo cortical loop. This allows it to synchronize oscillations generate by the basal ganglia during the preparation and execution of intended movements. One function of the loop is to carry movement instructions to the motor cortex through zona incerta output to the ventral lateral nucleus neurons in the cerebello thalamocortical loop and to brainstem motor neurons in the medial reticular formation and midbrain extrapyramidal area. This acts to synchronize the basal ganglia areas involved in planning and execution of the movement with those in the brainstem controlling axial and proximal limb
muscles with those areas in the motor cortex that control distal limb movements. In humans with Parkinson's disease, surgical lesion of the zona incerta alleviates their parkinsonian motor symptoms. Deep brain stimulation of the subthalamic nucleus in those with Parkinson's disease has identified the zona incerta as a promising target area for effective therapy. Unlike deep bilateral stimulation of the ventral lateral nucleus such stimulation of the zona incerta improves all aspects of tremor including both the distal and proximal parts of limbs and the body more generally. This also occurs without dysarthria and disequilibrium as this stimulation does not interrupt proprioceptive sensation and the processing of the fine motor skill movements of vocal cords. Researchers observed that "The ventral lateral nucleus has long been established as an effective surgical target for controlling distal limb tremor, including Parkinson Disease tremor. However, because it receives predominantly cerebellar afferents and no direct basal ganglia afferents, the reason why it is effective in controlling Parkinson Disease tremor has remained a paradox. The conduction of abnormal oscillations generated in the basal ganglia in Parkinson Disease to the ventral lateral nucleus via zona incerta would therefore explain this paradox and also explain why we observed such a potent anti tremor effect from stimulating zona incerta in our patients with Parkinson Disease"

The study further noted that deep brain stimulation upon the zona incerta "is effective in suppressing all components of tremor affecting both the distal and proximal part of the body. These results, if replicated in larger randomised controlled studies, have important implications for our current surgical management of patients with tremor and point to a more promising target area than the ventral lateral nucleus of the thalamus."

Central pain syndrome is pain initiated or caused by injury or dysfunction in the central nervous system. Recent research suggests that the development and maintenance of such pain could link to abnormal inhibitory regulation by the zona incerta of the posterior thalamus. It has been suggested that there exists a significant suppression of both spontaneous and evoked activity in inhibitory neurons in zona incerta and abnormally high spontaneous and evoked activity of neurons in posterior thalamus in animals with central pain syndrome. The positive association between behavioral and neurophysiological thresholds in rats with central pain syndrome is consistent with a causal role for suppressed incerto thalamic inputs in central pain syndrome.