Implications of asymmetric neural activity patterns in the basal ganglia outflow in the integrative neural network model for cervical dystonia

Cervical dystonia (CD) is characterized by abnormal twisting and turning of the head with associated head oscillations. It is the most common form of dystonia, which is a third most common movement disorder. Despite frequent occurrence there is paucity in adequate therapy, much of which is attributed to its uncertain pathophysiology. Recently we proposed a unifying network model highlighting the role of head neural integrator (hNI) for the pathophysiology of CD. According to our hypothesis the CD is due to abnormal output of hNI; the latter itself is not affected but its dysfunction is secondary to abnormal feedback. We hypothesized that asymmetry in the feedback to hNI is associated with severity in CD; the feedback asymmetry is greater in CD with lateralized head postures, such as turning of head in yaw plane (torticollis) or roll plane (laterocollis). The hypothesis also specifies that feedback to hNI-cerebellum, proprioception, and basal ganglia outflow (pallidus) are connected in a network; thus asymmetry is distributed through the feedback network. In 15 CD patients undergoing deep brain stimulation (DBS) surgery, with their informed consent, we used the opportunity to collect single unit neural responses and local field potential from the globus pallidus to measure whether feedback to hNI is asymmetric. Using machine learning algorithms developed to analyze single unit data, we found: (1) globus pallidus interna (GPi) firing rate, discharge pattern and gamma oscillation were asymmetric in patients with robust torticollis; (2) there was no asymmetry in these parameters in retrocollis; and (3) in those patients with oppositely directed laterocollis and torticollis. Firing rate was higher in GPi cells ipsilateral to the direction of head rotation; the asymmetry was more pronounced in tonic cells compared to burst neurons. In addition to confirming that CD is associated with an asymmetric pallidal activity, our data showed that neuronal asymmetry correlated with the degree of involuntary head turning. We propose that asymmetric pallidal activity results in asymmetric feedback to hNI causing its dysfunction.