The ventrolateral (VL) thalamus is comprised of ventral oral posterior (Vop) nucleus, ventralis oralis internus (Voi), and the VIM nucleus (Hassler 1959). Anterior and lateral to these nuclei lie the reticular nucleus of the thalamus and the internal capsule (El-Tahawy et al. 2004). The VL thalamus mediates motor control. It receives afferent fibers from the cerebellum, basal ganglia, cerebral cortices, and spinal cord, and it projects efferent fibers to the cerebral cortices and basal ganglia. The VL has two subcortical afferent territories: the pallidothalamic and cerebellothalamic territories (Ilinsky and Kultas-Ilinsky 1987; Kuo and Carpenter 1973; Nakano 2000; Sidibé et al. 1997). The density of the pallidothalamic territory decreases in an anterior to posterior gradient and that of the cerebellothalamic territory decreases in a posterior to anterior gradient in the VL thalamus (Sakai et al. 1996). These two territories are widely interdigitated (Asanuma et al. 1983a, b; Sakai et al. 1996). The Vop preferentially receives inhibitory pallidothalamic inputs from the globus pallidus internus (GPi), and the VIM predominantly receives excitatory inputs from the cerebellum. The efferents from the VIM nucleus preferentially project to the primary motor, premotor, and proper supplementary motor area, which, in turn, provide reciprocal excitatory corticothalamic inputs (Bromberg et al. 1981; Hoover and Strick 1999). The VIM nucleus projects predominantly to the deep cortical areas of the motor cortex (Area 4 and possibly, Area 3a), which respond to the passive motor movements of joints (Anderson and Turner 1991; Butler et al. 1992; Jones 2007; Miyagishima et al. 2007; Vitek et al. 1994). The VIM neurons are somatotopographically organized; the face, forelimb, and hindlimb receptive fields are arranged medially to laterally (Strick 1976; Vitek et al. 1994; Kurata 2005). The Vc nucleus, which is the major termination structure of the medial lemniscus, projects to the primary somatosensory cortex (El-Tahawy et al. 2004). The subthalamic area (STA) is located ventrally to the VL thalamus.

As the microelectrode descends toward the thalamic target, the caudate has a very slow rate of spontaneous discharge (0–10 Hz) (Vitek et al. 1998), and the thalamus is relatively quiet in the awake patient but shows occasional slow bursting activity (Starr et al. 1998). Microelectrode entry into the motor thalamus can be indicated by the identification of movement-responsive cells and/or cells discharging at tremor frequency (Lenz et al. 1994). Microelectrode recording can identify the Vc nucleus, which is a tactile relay nucleus, and its anterior border with VIM as well as the ventral border with STA (El-Tahawy et al. 2004). Neurons that respond to voluntary movements (voluntary cells) are predominantly present in the Voa and Vop (El-Tahawy et al. 2004). Voluntary cells do not respond to verbal commands but rather to the voluntary act itself, and they are sometimes difficult to distinguish from kinesthetic cells (El-Tahawy et al. 2004; Raeva et al. 1999). Kinesthetic cells receive afferents from muscle spindles that are located in the tendons and muscle bellies or from stretch receptors that are located in the tendons, joint capsules or deep tissues, and they respond to passive joint movements and proprioceptive afferents. These cells are located just anterior to the tactile receptive field (Ohye and Narabayashi 1979; Ohye et al. 1989). Tactile cells in the Vc nucleus respond to superficial light touch. Stimulation of the Vc nucleus induces paresthesia due to activation of the medial lemniscal axons (El-Tahawy et al. 2004).

Vim DBS reduces abnormal tremor-electromyography coherence in ET postural tremor (Vaillancourt et al. 2003). The ideal target for abolishing the tremor is supposed to be located in the area where kinesthetic and tremor cells coexist (Lenz et al. 1994; Atkinson et al. 2002). The kinesthetic zone is located in the lower and lateral part of the VIM nucleus, which is a region of confluence of cerebellothalamic and spinothalamic tracts and which sends the majority of its axons to the motor cortex (Percheron et al. 1996). Ohye and colleagues have postulated that this area is optimal for radiofrequency lesioning to abolish tremor (Ohye and Narabayashi 1979; Ohye et al. 1989). Kiss et al. (2003) have reported that there is an expansion of the representation of movement-related (kinesthetic and deep-responding) neurons anteriorly in patients with tremor. Although DBS of the lateral portion of the VIM nucleus, where tremor cells might play a predominant role, provides the best control of parkinsonian tremor, as suggested previously (Atkinson et al. 2002; Hariz and Hirabayashi 1997), this is not the case for ET and post-stroke tremor, in which, presumably, the tremor cells are spread out in wide areas (Katayama et al. 2005) and they involve more proximal muscle components, which are represented more anteriorly and dorsally in the VIM nucleus (Ohye et al. 1989). A clinical study that examined the relationship between lead location and clinical outcome of 57 leads in 37 ET patients revealed that the lead locations in the anterior margin of the VIM nucleus corresponded to significant improvements in tremor scores (Papavassiliou et al. 2004). In such cases, thalamic DBS with bipolar stimulation or a low angle of the DBS electrode to the anterior commissure–posterior commissure (AC–PC) line (~45°) is advocated, as this could cover the more anterior (Katayama et al. 2005; Kobayashi et al. 2010; Yamamoto et al. 2004; Kiss et al. 2003) and dorsal areas (Kiss et al. 2003; Nguyen and Degos 1993).

The PSA and its vicinity comprises the nuclei area, which includes the Zi, the STN, and substance Q of Sano, and the fiber area, which includes the ansa lenticularis, Forel’s fields H, H1, and H2, Raprl, perirubral fibers, and rubrothalamic fibers (Carrillo-Ruiz et al. 2012). There also exist extended nuclei from mesencephalon that correspond to the substantia nigra (SN) and red nucleus (RN). The PSA is situated anterolateral of the red nucleus, posteromedial of the STN, inferior of the ventral thalamic nuclei, superior of the SN, and anteromedial of the posterior limb of the internal capsule (Xie et al. 2012; Fytagoridis et al. 2013a).

The Zi consists of four territories: rostral, dorsal, ventral, and caudal. Rostral Zi, which is attributed to visceral control, is located dorsomedial to the pallidofugal fibers and STN. Dorsal Zi is attributed to the wake and ventral Zi is under the guidance of the eye and head movements (Carrillo-Ruiz et al. 2012). The cZi, which is called the motor part of the Zi, extends posterior to the STN (Carrillo-Ruiz et al. 2012). The cZi is situated ventral to the Va thalamic nucleus, just ventral to the fascicularis thalamicus (Forel’s fields H), and dorsal to the fascicularis lenticularis (Forel’s fields H2) (Morel 2007; Plaha et al. 2008). Medial to the cZi is situated the cerebellothalamic tract and the red nucleus, and, lateral to the cZi, exists the internal capsule. The Zi receives inputs from motor, associative, and limbic cortices, the interpositus nucleus of the cerebellum, the substantia nigra reticulata (SNr), the globus pallidus internus (GPi), and the ascending reticular activating system, and it then connects to the centromedian and parafascicular (CM/Pf) and VL nuclei of the thalamus, SNr, GPi, the parvocellular RN, ION, the medial reticular formation, the pedunculopontine tegmental nucleus, the interpositus nucleus of the cerebellum, hypothalamus, the brainstem, including the pedunculopontine nucleus, the spinal cord, and the cerebral cortices (Carrillo-Ruiz et al. 2012; Heise and Mitrofanis 2004; Mitrofanis et al. 2004; Mitrofanis 2005; Plaha et al. 2008). cZI is an extension of the reticular thalamic nucleus, and it predominantly consists of GABAergic neurons. It affects both the basal ganglia and cerebellar outputs, medial reticular formation, and midbrain reticular formation, which are involved in controlling axial and proximal limb muscles (Blomstedt et al. 2009; Plaha et al. 2008). Current theories suggest that the cZi might play a key role in transmitting GABAergic input from the basal ganglia to the cerebellothalamocortical circuits and that DBS might alter or inhibit abnormal oscillations (Blomstedt et al. 2009; Fytagoridis et al. 2012; Plaha et al. 2008). Plaha et al. (2008) have suggested that Zi is an effective target for various types of tremors.

The Raprl is situated inferior to the Vo and VIM thalamic nuclei, in front of the lemniscus pathway, externally is the thalamic reticular nucleus, Zi, and STN, and the medial side is bordered by the RN (Carrillo-Ruiz et al. 2008, 2012; Lehman and Augustine 2013; Morel 2007). The Raprl contains cerebellothalamic, pallidothalamic, renticulothalamic, and rubrothalamic fibers (Carrillo-Ruiz et al. 2008, 2012).

When PSA DBS is performed, the transfrontal trajectory to the target is ~45° to the AC–PC plane, and an abrupt increase in impedance (from 400–500 to 600–700 Ω) is experienced when the electrode is passed beyond the ventral boundary of the thalamus into the subthalamic white matter (Murata et al. 2003; Plaha et al. 2008). Alternatively, single-unit-activity recordings have demonstrated frequencies of at least 15 Hz and/or responses to somatosensory stimulation or joint movements in the thalamus, while single-unit activity is absent or below 5 Hz with low background activity and does not respond to outer stimuli in the subthalamic area (Raprl) (Herzog et al. 2007; Kiss et al. 2003). In awake humans, late components of the somatosensory evoked potential from median nerve stimulation can be recorded from Raprl (Blomstedt et al. 2009). The extracellular action potential characteristics of the anterior thalamus and Zi are similar: low frequency and irregular discharge. The major difference is the neuronal density or the distance traversed before extracellular action potentials are encountered (Baker et al. 2004). In the Zi, the neuronal density is lower than that of the anterior thalamus. When the microelectrode enters into the STN, high frequency irregular discharges and increases in background activity are notably observed (Theodosopoulos et al. 2004). Just outside the bottom of the STN is an electrically quiet zone. When the microelectrode enters into the SNr, high frequency regular discharges with decreased background activity are detected.