In the early to middle stages of Huntington's disease, increased dopamine and norepinephrine lead to which effect on thalamocortical activity?

• A. Thalamocortical excitation
• B. Thalamocortical inhibition
• C. No change in thalamocortical activity
• D. Global cortical suppression

Answer: (A)

In Huntington’s disease, early to middle stages show reduced output from the indirect pathway due to loss of striatal neurons that normally inhibit the external segment of the globus pallidus. Dopamine enhances the direct pathway (via D1 receptors) and dampens the indirect pathway (via D2 receptors), so a rise in dopamine shifts the balance toward direct pathway activity. This reduces the inhibitory influence of GPi on the thalamus, effectively disinhibiting thalamocortical circuits. Norepinephrine adds to this by boosting cortical arousal and further facilitating thalamocortical transmission. The net result is increased thalamocortical excitation, which aligns with the hyperkinetic movements seen in this stage.