From the Guidelines
The thalamocortical circuit plays a crucial role in the pathophysiology of paroxysmal kinesigenic dyskinesia (PKD), with abnormal connectivity between the thalamus and motor cortex contributing to the disease's symptoms. The thalamocortical circuit is a complex neural pathway that connects the thalamus to the cerebral cortex, and its dysfunction has been implicated in various neurological conditions. In the context of PKD, studies have shown that the abnormal basal ganglia−thalamo−cortical circuit is the pathophysiological basis of the disease 1. Functional magnetic resonance imaging (MRI) studies have revealed an abnormal connectivity between the thalamus and the motor cortex in patients with PKD, which is associated with the duration of the disease 1.
Key Findings
- The PRRT2 gene is a major causative gene for PKD, and its mutations can lead to presynaptic dysfunction, abnormal neurotransmitter release, and lack of negative regulation of Na+ channels 1.
- The thalamo−prefrontal hypoconnectivity has been observed in patients with PRRT2 mutations, indicating inefficient thalamo-prefrontal integration and dysfunction of motor inhibition 1.
- The core pathogenesis of PKD is the disturbed cell excitability caused by PRRT2 mutation, which is associated with presynaptic dysfunction, abnormal neurotransmitter release, and the lack of negative regulation of Na+ channels 1.
Clinical Implications
- The thalamocortical circuit's dysfunction in PKD highlights the importance of considering the neural circuitry involved in the disease's pathophysiology when developing treatment strategies.
- Further research is needed to fully understand the mechanisms underlying the thalamocortical circuit's dysfunction in PKD and to develop effective treatments that target this circuit.
- Approximately one-half of patients with primary PKD do not harbor mutations in the known disease-causing genes, suggesting the existence of other disease-causing genes and the need for further research into the genetic basis of the disease 1.
From the Research
Thalamocortical Circuit Overview
- The thalamocortical circuit is a complex network that plays a crucial role in various brain functions, including sensory transmission, cognition, and motor control 2, 3, 4.
- This circuit consists of excitatory neurons in the thalamus that are connected to the cortex, and its dysfunction has been implicated in various neurological and psychiatric disorders, such as chronic pain and epilepsy 2, 5, 6.
Thalamocortical Circuit Dysfunction in Chronic Pain
- Studies have shown that chronic pain is associated with altered functional connectivity and modular architecture of the thalamocortical circuit 2, 6.
- The thalamus serves as a primary relay center for transmitting sensory information and motor impulses, and its dysfunction can lead to abnormal pain perception 2, 6.
- Research has also identified correlations between pain intensity and resting-state functional connectivity of the thalamo-somatosensory pathway in patients with chronic low back pain 6.
Thalamocortical Circuit Motifs and Organization
- The thalamus is composed of excitatory neurons that are devoid of local recurrent excitatory connectivity, and understanding its long-range, input-output connectivity patterns is critical for building functional models 4.
- A new classification of thalamocortical motifs has been proposed, where structure naturally informs function, and this framework can help elucidate the role of the thalamus in cognition and other brain functions 4.
- The thalamocortical circuit is also involved in generalized epilepsy, and elucidating its mechanisms may lead to new opportunities for treatment 5.