Asymmetric pallidal neuronal activity in patients with cervical dystonia

Abstract

The origin of asymmetric clinical manifestation of symptoms in patients suffering from cervical dystonia (CD) is hitherto poorly understood. Dysregulated neuronal activity in the basal ganglia has been suggested to have a role in the pathophysiology of CD. Here, we re-assessed the question to what extent relative changes occur in the direct vs. indirect basal ganglia pathway in CD, whether these circuit changes are lateralized, and how these alterations relate to CD symptoms. To this end, we recorded ongoing single cell and local field potential (LFP) activity from the external (GPe) and internal pallidal segment (GPi) of 13 CD patients undergoing microelectrode-guided stereotactic surgery for deep brain stimulation in the GPi. We compared pallidal recordings from CD patients operated under local anaesthesia (LA) with those obtained in CD patients operated under general anaesthesia (GA). In awake patients, mean GPe discharge rate (52 Hz) was lower than that of GPi (72 Hz). Mean GPi discharge ipsilateral to the side of head turning was higher than contralateral and correlated with torticollis symptom severity. Lateralized differences were absent at the level of the GPe and in recordings from patients operated under GA. Furthermore, in the GPi of CD patients there was a subpopulation of theta-oscillatory cells with unique bursting characteristics. Power and coherence of GPe– and GPi–LFPs were dominated by a theta peak and also exhibited band-specific interhemispheric differences. Strong cross-frequency coupling of low-gamma amplitude to theta phase was a feature of pallidal LFPs recorded under LA, but not GA. These results indicate that CD is associated with an asymmetric pallidal outflow. Based on the finding of symmetric neuronal discharges in the GPe, we propose that an imbalanced interhemispheric direct pathway gain may be involved in CD pathophysiology.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism

“…Micro-tip impedances were 0.8 ± 0.1 MOhm (range 0.5e1.0). Starting at 10 mm above the surgical target, electrodes were advanced in steps of 500 mm and ongoing activity was recorded at each site for at least 20 s. In agreement with previous observations [12], under general anaesthesia with propofol/remifentanil, unit activity in both pallidal segments was often indistinguishable and characterized by a multitude of different activity levels and patterns, respectively. Therefore, the occasional recording of highly regular "border cell" discharges at 20e30 Hz proved to be especially helpful for a delineation of peri-pallidal white matter layers and for an on-line differentiation between the GPe and GPi, respectively.…”

Neurophysiologisches Monitoring in der funktionellen Neurochirurgie bei Bewegungsstörungen: Intraoperative Mikroelektrodenableitungen

“…Im GPe von Patienten mit segmentaler bzw. fokaler zervikaler Dystonie findet man ein vergleichbares Aktivitätsniveau [30,45,50]. In der Grenzlamelle am Übergang zum GPi registriert man wieder die Aktivität von Grenzzellen (siehe oben).…”

“…In der englischsprachigen Literatur werden diese Zellen als ,,high frequency discharge neurons" bezeichnet. Die mittlere Entladungsrate von Nervenzellen im posteroventrolateralen GPi von Parkinsonpatienten ist mit 70-90 Hz [8,18,19,27,29,45,50,53,56] deutlich höher als die durchschnittliche Aktionspotential-Frequenz im GPi von Patienten mit Dystonie (50-70 Hz) [30,45,50,56]. Der Unterschied in der Entladungsrate zwischen GPe und GPi kann bei iMEA im Pallidum von Patienten mit Morbus Parkinson die Differentialdiagnose zwischen beiden Kerngebieten erleichtern [29].…”

“…Der Unterschied in der Entladungsrate zwischen GPe und GPi kann bei iMEA im Pallidum von Patienten mit Morbus Parkinson die Differentialdiagnose zwischen beiden Kerngebieten erleichtern [29]. Bei Dystoniepatienten hingegen ist die Differenzierung zwischen GPe und GPi schwieriger, da Entladungshäufigkeit und -muster beider Kerne große Ähnlichkeiten aufweisen [30,45,50]. In solchen Fällen liefert die sorgfältige Kartierung von Grenz-Zellen wertvolle lokalisatorische Informationen (siehe oben).…”

Basal ganglia: physiological, behavioral, and computational studies

“…In one study, Moll et al (2014) recorded single cell as well as local field potential activity from globus pallidus (internal and external segments) in patients with cervical dystonia undergoing deep brain stimulation. They found that cervical dystonia is associated with asymmetric pallidal functions.…”