New Targets for Deep Brain Stimulation Treatment of Parkinson's Disease

Anna Castrioto; Elena Moro


Expert Rev Neurother. 2013;13(12):1319-1328. 

In This Article

The Posterior Subthalamic Area/cZi

Recently, the posterior subthalamic area (PSA) has been suggested as an alternative DBS target for PD (Table 2). This is not a new target, because lesions had extensively been done in this area for the control of tremor.[44–46] The PSA is located below the ventral thalamus, lateral to the red nucleus and posteromedial to the STN.[46] It includes the zona incerta (ZI) and the prelemniscal radiation. The ZI is a small cellular nucleus that covers the STN, lying between the fields of Forel. The pallidothalamic tract is composed by the ansa lenticularis and the fasciculus lenticularis (or Forel field H2), both taking origin from the GPi.[47] The two fibers tracts merge into the fasciculus thalamicus (or Forel field H1) before entering the thalamus. The pallidothalamic fibers surround dorsally and medially the STN, separating it from the ZI rostromedially and from the prelemniscal radiation and the red nucleus more medially.[48] The cerebellothalamic tract connects the deep cerebellar nuclei with the thalamus passing through the superior cerebellar pedunculus and its decussation, and to the red nucleus anteriorly.[47]

Several surgical centers have investigated the effects of PSA stimulation, with different groups using a different nomenclature. Plaha et al. refer to this area using the term cZi to distinguish between a caudal and a more rostral part.[48] Stimulation of this area seems to provide an optimal control of tremor, rigidity and to some extent of bradykinesia as well (Table 2),[49–52] possibly even better than STN stimulation.[48] Nevertheless, these findings should be taking cautiously since the experience with cZi DBS is little (the number of patients included is small and no randomized studies are available). Moreover, potential chronic side effects might prevent from taking advantage of the actual improvement. Speech worsening in patients with STN stimulation can be related to electrodes located more medially,[53] probably due to the current spread to the cerebellothalamic tract. Moreover, diffusion of current to the pallidothalamic fibers, located medially to the STN, could block the effects of levodopa (reducing dyskinesia, but worsening bradykinesia and freezing).[54–57] Thus, stimulation of this area can be complicated on one hand by the occurrence of dysarthria and postural instability, linked to the diffusion of current to the cerebellothalamic tract,[58] and to the other hand by blocking levodopa effects.

A few studies have investigated the effect on speech of the cZi stimulation compared with STN stimulation.[59–61] A recent study has shown that whereas stimulation within the STN increased voice intensity, stimulation within the cZi worsened it.[59] Karlsson et al. found a more detrimental effect on articulation of speech by cZi compared with STN stimulation.[61]