Is the medial subthalamic region in humans homologous to that in rodents? Relevance to neuropsychiatric disorders and their treatment with DBS

Biol Psychiatry. 2025 May 16:S0006-3223(25)01191-6. doi: 10.1016/j.biopsych.2025.05.007. Online ahead of print.

ABSTRACT

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is an effective treatment for patients with refractory neuropsychiatric disorders such as Parkinson’s disease and obsessive-compulsive disorder. The mechanisms of DBS are not well understood and may involve adjacent structures. They are also associated with many side effects. The medial subthalamic region (MSR) has been characterized in humans as an anatomical target of the hyperdirect pathway originating in limbic cortical areas. However, no clearly identified cell clusters or nuclei have been described. In contrast, the rodent MSR receives inputs from the limbic cortex, but contains well-defined nuclei, including the so-called parasubthalamic nucleus. Comparison of neurochemical and hodological data suggests that the MSR is homologous in rodents and humans. In addition, nuclei of the rodent MSR are involved in functions that are compatible with many of the side effects associated with DBS of the STN in humans. These observations underscore the need for further investigation of this region in both humans and rodents, which should prove beneficial in the treatment of neurological and neuropsychiatric disorders.

PMID:40383218 | DOI:10.1016/j.biopsych.2025.05.007