Deep-brain stimulation, in short DBS, is one of the most promising surgical treatments for movement disorders such as Parkinson’s disease (PD), and more recently, neuropsychiatric diseases such as obsessive compulsive disorder. During DBS surgery, a microelectrode is lowered deep into the brain with the aim to stimulate small subcortical nuclei in order to alleviate disease related symptoms such as rigidity and tremor as seen in patients with PD. Studies using DBS in PD patients show that a suboptimal placement of electrodes in, for example, the Subthalamic Nucleus (STN) or Globus Pallidus (GP), can yield changes in cognitive processes (e.g. attention, mental speed, response inhibition) and affective states (e.g. depression, hypomania, anxiety, hypersexuality, and hallucinations). These unwanted side effects of DBS are speculated to be the result of the stimulation of subareas other than the motor zone within these nuclei. At the same time it is possible that there are more efficient target areas in the human subcortex to alleviate disease-related symptoms while limiting side effects.
The human subcortex is a highly crowded brain area, which consists of hundreds of unique, small grey matter nuclei constituting approximately ¼ of total human brain volume. Importantly, only approximately 7% of these nuclei are currently accessible in standard human brain magnetic resonance imaging (MRI) atlases (Forstmann et al., 2016). This low percentage can have several imaging related causes, including the small size of subcortical nuclei as compared to the voxel size, which is particularly relevant when applying 1.5 or 3 Tesla (T) MRI. Additionally, the challenges posed by the large distance of the subcortex from the head coil may be a cause. In light of the vast amount of uncharted brain areas, one can also think of the human subcortex as ‘terra incognita’. The aim of this proposal is to chart ‘terra incognita’ to create a tool to identify and localize new targets for DBS.
With the ERC PoC entitled ‘Atlas’ we have created probabilistic atlas maps with unprecedented detail as well as a 3D app for educational purposes both in the clinical and basic neurosciences. These efforts are currently extended potentially leading to a commercial product.
Probabilistic atlas papers:
Alkemade, A., Mulder, M. J., Trutti, A. C., & Forstmann, B. U. (2021). Manual Delineation approaches for direct imaging of the subcortex. Brain Structure and Function.
Trutti, A. C., Fontanesi, L., Mulder, M. J., Bazin, P. L., Hommel, B., & Forstmann, B. U. (2021). A probabilistic atlas of the human ventral tegmental area (VTA) based on 7 Tesla MRI data. Brain Structure and Function, 226(4), 1155-1167.
Alkemade, A., Pine, K., Kirilina, E., Keuken, M. C., Mulder, M. J., Balesar, R., Groot, J. M., Bleys, R. L. A. W., Trampel, R., Weiskopf, N., Herrler, A., Moeller, H. E., Bazin, P.-L. & Forstmann, B. U. (2021). 7 Tesla MRI followed by histological 3D reconstructions in whole-brain specimens. Frontiers in Neuroanatomy, 14, 68.
Bazin, P.-L. Alkemade, A., Mulder, M. J., Henry, A. G., & Forstmann, B. U. (2020). Multi-contrast anatomical subcortical structure parcellation. eLife, 9:e59430.
Alkemade, A., Mulder, M., Groot, J., Isaacs, B., van Berendonk, N., Lute, N., Isherwood, S., Bazin, P.-L. & Forstmann, B. U. (2020). The Amsterdam Ultra-high field adult lifespan database (AHEAD): A freely available multimodal 7 Tesla submillimeter magnetic resonance imaging database. NeuroImage, 221, 117200.
3D app:
Miletić, S., Bazin, P.-L. Isherwood, S. J. S., Keuken, M. C., Alkemade, A., & Forstmann, B. U. (in press). Charting human subcortical maturation across the adult lifespan with in vivo 7T MRI. NeuroImage.
