Original article
Effect of deep brain stimulation of GPI on neuronal activity of the thalamic nucleus ventralis oralis in a dystonic patientEffet de la stimulation du GPI sur l’activité neuronale enregistrée dans le noyau ventral antérieur du thalamus d’un patient dystonique

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Abstract

Objective. – To record the possible effect of acute deep brain stimulation (DBS) of the globus pallidus internus (GPI) on the neuronal activity of the ventralis oralis anterior (VOA) nucleus of the thalamus.

Methods. – Under general propofol anaesthesia, extracelullar single unit recordings were performed in VOA of a post-anoxic dystonic patient previously implanted with GPI located electrodes for chronic DBS.

Results. – Neurons recorded in the VOA could be classified in two cell subpopulations: a high firing rate (16.5 Hz) and low burst index (BI; 15.6) type and a low firing rate (5.5 Hz) and high BI (35.6) type. GPI electrical stimulation reduced the frequency and increased the BI of the high firing rate cells while leaving the other cell type unchanged.

Conclusion. – These results demonstrate that pallidal DBS is able to inhibit a subpopulation of motor thalamic cells and question the pathophysiological model of dystonia based on a low firing rate of GPI cells.

Résumé

Objectif. – Nous avons pu enregistrer la modulation de l’activité électrique dans le noyau ventral antérieur du thalamus (VOA) suite à une stimulation électrique du globus pallidus internus (GPI).

Méthode. – Sous anesthésie générale par propofol, des enregistrements unitaires extracellulaires ont été recueillis dans le VOA chez un patient souffrant d’une dystonie post anoxique. Celui-ci avait été implanté précédemment dans le GPI dans le cadre d’un traitement par DBS.

Résultats. – Les neurones enregistrés dans le VOA ont pu êtres classifiés en deux  sous populations. Une première famille de neurones déchargeait à une fréquence moyenne élevée (16,5 Hz) et présentait un index moyen de bouffées (BI, mesurant la propension d’une cellule à décharger en bouffées) de 15,6, alors qu’une deuxième famille déchargeait à une fréquence moyenne plus basse (5,5 Hz) avec un BI moyen de 35.6. La stimulation électrique du GPI réduisit la fréquence et augmenta le BI de la première famille de neurones sans modifier les propriétés de décharge de la deuxième.

Conclusion. – Ces résultats démontrent que la stimulation pallidale inhibe une sous population de neurones du thalamus moteur. Ils remettent en question l’hypothèse physiopathologique sous tendant le syndrome dystonique reposant sur une diminution de la fréquence de décharge des cellules du GPI.

Introduction

The current anatomo-functional knowledge of basal ganglia based on animal studies allows some understanding about the pathophysiology of Parkinson’s disease [2], [3], [7], [8]. However, our pathophysiological hypotheses concerning dystonia are far less advanced and even puzzling. Indeed, according to the Alexander’s model, inhibition of the globus pallidus internus (GPI) activity should lead to a disinhibition of the motor thalamus, and therefore, to an overall increase in motility. This is in contradiction with the fact that pallidotomy or deep brain stimulation (DBS) of the GPI can improve generalised or focal dystonia [6], [13], [15], [21], [24].

We had the opportunity to record single unit activities in the ventralis oralis anterior (VOA) thalamic nucleus of a 26-year-old patient who developed a post-anoxic, delayed generalised dystonia. Magnetic resonance imaging (MRI) showed bilateral post-anoxic lesions in the globus pallidus, (Fig. 1A), occipital lobes and cerebellum. Several medications (L-dopa, tizanidine, baclofene, tetrabenazine) could not relieve the symptoms significantly; therefore, the patient gave his informed consent for bilateral stereotactic implantation of DBS electrodes in GPI. As neither clinical improvement nor deterioration was observed during the first month, the patient underwent placement of new bilateral DBS electrodes in the VOA 1 month later while leaving the pallidal DBS electrodes in situ. Post-operative MRI confirmed the VOA localisation of the DBS electrodes (Fig. 1B). This procedure allowed us to record the effect of acute per-operative pallidal DBS on the firing rate of VOA neurons. After 4 months of high-frequency VOA stimulation, the patient showed major improvement in dystonia. He regained independence, became ambulant, but committed suicide despite close medical and psychiatric managements (for details on clinical status see Ghika et al. [10]). Autopsy findings revealed patchy distribution of glial scars resulting from old hypoxic necroses in the caudate and putamen, together with old cystic lesions in the external pallidum. The medial part of the GPI was the best preserved and the thalamus was without hypoxic damage. The difference between the hypoxic lesions and the recent thin canal generated by passage of the electrodes was clear-cut, allowing us to determine that the pallidal DBS electrodes reached the most medial segment of the preserved GPI and that the thalamic DBS electrode contacts were located in the VOA on both sides (for a more detailed description see Ghika et al. [10]).

Section snippets

Materials and methods

Using the CRW stereotactic system (Radionics, Burlington, USA) under general propofol anaesthesia, the VOA stereotaxic localisation was determined using MRI (1.5 T) and the Schaltenbrand and Wahren atlas [19] as following: 5 mm above the intercommisural plane, 2 mm anterior to the midcommisural point, and 10 mm lateral to the midline. The connectors of the previously implanted GPI DBS electrodes were exposed and used for per-operative stimulation. The VOA DBS electrodes were inserted through

Results

The correct positioning of the stimulating electrodes in GPI and VOA on both sides was confirmed using control MRI (Fig. 1B) and by direct anatomic brain examination (see [10]). About 8–4 mm anterodorsal to the target, nine single units were recorded in the thalamic dorso-oralis internus (DOI) nucleus. The mean duration of their action potentials was 1.5 ± 0.2 ms and their mean discharge frequency 7.1 ± 1.4 Hz. Based on visual examination and BI computation, six cells were classified as

Discussion

This case report shows that DBS of GPI can reduce the firing rate of VOA neurons. These cells could be classified into two cell types: a high firing rate type (16.5 Hz) and a low firing rate type (5.5 Hz). Noteworthy, despite the burst suppression effect of propofol anaesthesia on surface EEG [1] and the different pathology in presence (dystonia vs. Parkinson), this classification is in keeping with that of Raeva et al. [17], [18] who demonstrated that VOA neurons could be segregated as type A

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