Discussion

Surgical thalamic targets in the light of connectivity.

The unique feature of the atlas plates presented here is that unlike those in other stereotactic atlases of the human brain the outlines of thalamic nuclei shown in three standard stereotactic planes are from the same brain. This ensures high compatibility of the target coordinates in the three planes as well as facilitates co-registration of the 3D volume with individual MRI’s. Another important feature is that in addition to the cytoarchitecture the outlines of the motor thalamic nuclei are based on experimental data from tracing of subcortical connections in nonhuman primates and extrapolating these to human thalamus using an immunocytochemical marker that brings out specific features of each subcortical afferent territory (Ilinsky and Kultas-Ilinsky, 1987; Mason et al., 2000; Kultas-Ilinsky et al., 2011See references on BIBLIOGRAPHY page).

During the early period of stereotactic interventions in the human thalamus discussion of neurosurgeons centered on the question of which of the three nuclei Vim, Vop or Voa of Hassler) is the most efficient for elimination of Parkinsonian tremor. The radiological coordinates of targets were compared and histological analyses of available postmortem samples were performed. The results were then related to clinical outcomes of the cases. Eventually consensus developed that lesions placed in Vim and/or Vop of Hassler provided the best clinical results.

At present with the use of modern non-invasive visualization techniques (see review by Frey et al., 2022 [1]) the focus is on how to identify location of ‘Vim’ in brain MR images. Various approaches have been proposed. Still the remarkable resolution provided by modern MRI scanners and scanning protocols are not sufficient for resolving individual nuclei within the large area supplied by motor and somatosensory afferents to the thalamus. However, proposed creative image processing techniques can help in improving it (Corona et al. 2020 [2]). Moreover the use of tract density imaging for simultaneous tracing of connections from cortical and subcortical areas is also very helpful approach (Behrens et al., 2003 [3]; Middlebrooks et al., 2018 [4]; Akram et al. 2018 [5]; Akram et al., 2019 [6]; Coenen et al., 2020 [7]). Point of the overlap of fibers from the primary motor cortex and those from cerebellum that are destined to the thalamus, has been considered to be Vim and used as the surgical target. Results show that stimulating electrodes in this location are indeed very effective (Akram et al., 2018). At the same time comparison of different cases reveals a rather wide spread of effective points that do not all fit into probabilistic Vim. (Fereira et al., 2020 [8]. Besides individual variability used to explain these findings there is another important aspect here that has not attracted much attention. Namely, the problem may be semantic as the majority of the points are still confined to the same larger area that we call ventral VL (VLv). In our thalamic maps VL refers to the entire cerebellar afferent territory that occupies a substantial part of the thalamus and extends from about 4.50mm medially to 18.00mm laterally whereas its ventral part reaches the ac-pc plane only between 12.5 mm and 15.75 mm from the midline. Consequently Hassler’s Vim and most of the Vop are both part of the ventral VL. Thus Vim and Vop both being an integral part of the extensive cerebellar afferent receiving territory in the thalamus are histologically and functionally identical, and location wise correspond to our VLv. It is this ventral part of VL that over several decades has been proven to be the best target for elimination of tremor (Hassler et al., 1979 [9]; Lenz et al., 1995 [10]; Benabid et al., 1996 [11]; Hamani et al., 2006 [12]). The modern in vivo tract tracing techniques often show probabilistic Vim at the ventralmost boundary of the thalamus almost below grey matter [8]. At the same time the resolution of provided illustrations is not sufficient to resolve the anatomical details of the area therefore it is not clear whether the spot is in the grey or white matter.  In a recent study by Neudorfer et al., 2022 [13] a subthalamic ‘hypointensity region’ in FGATIR MR images was identified that proved to be clinically the best target for tremor elimination with DBS.  It should be kept in mind that cerebellothalamic fibers enter VL  at almost all its mediolateral coordinates but their highest density in the subthalamus is at the level of ventral VL and situated under it VPi (ventralposterior inferior nucleus a component of somatosensory territory). Thus, this subthalamic region with the highest concentration of cerebellothalamic fibers (erroneously labeled in the current literature as dentatorubro thalamic tract or DRT), as well as the ventral VL are both implicated as effective DBS targets. However, the exact anatomical structure responsible for the positive clinical results still needs to be determined. Comparison of mediolateral stereotactic coordinates of effective spots as well as establishing their positions relative to the ac-pc plane can be useful for finding anatomical correlates.

In solving this dilemma of grey vs white matter the present atlas may be of help as it has been successfully co-registered with MNI space and it would be interesting to see whether it can be applied in individual surgical cases provided that fast and efficient software can be designed. Together with algorithms, which show highly accurate registration of MNI space resources to individual patient brains (Ewert et al., 2018 [14]), the application of a standardized atlas as the present one bears potential in translational clinical neuroscience.

References:

[1] doi: 10.3389/fneur.2022.825178

[2] https://onlinelibrary.wiley.com/doi/10.1002/hbm.24933

[3] Nat Neurosci 6:750–757. https://doi.org/10.1038/nn1075

[4] Neuroimage Clin.2018;20:1266-1273. https://doi.org/10.1016/j.nicl.2018.10.009

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790021/pdf/main.pdf  

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543124/

[7] doi: 10.1016/j.nicl.2020.102165;

[8]  https://www.biorxiv.org/content/10.1101/2020.08.05.236679v1.full

[9]  Stereotaxis in Parkinson Syndrome, 1979, Heidelberg: Springer

[10] Neurosurgery, 1995, Mov Dis 10:318-328

[11] J. Neurosurg. 1996, 84:203–214

[12]  Neurosurgery, 2006, 58:146–158.  pmid: 16385339

[13] https://doi.org/10.1002/ana.26326

[14] https://doi.org/10.1016/j.neuroimage.2018.09.061