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Evolving characterization of the human hyperdirect pathway

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Abstract

The hyperdirect pathway (HDP) represents the main glutamatergic input to the subthalamic nucleus (STN), through which the motor and prefrontal cerebral cortex can modulate basal ganglia activity. Further, direct activation of the motor HDP is thought to be an important component of therapeutic deep brain stimulation (DBS), mediating the disruption of pathological oscillations. Alternatively, unintended recruitment of the prefrontal HDP may partly explain some cognitive side effects of DBS therapy. Previous work describing the HDP has focused on non-human primate (NHP) histological pathway tracings, diffusion-weighted MRI analysis of human white matter, and electrophysiology studies involving paired cortical recordings with DBS. However, none of these approaches alone yields a complete understanding of the complexities of the HDP. As such, we propose that generative modeling methods hold promise to bridge anatomy and physiology results, from both NHPs and humans, into a more detailed representation of the human HDP. Nonetheless, numerous features of the HDP remain to be experimentally described before model-based methods can simulate corticosubthalamic activity with a high degree of scientific detail. Therefore, the goals of this review are to examine the experimental evidence for HDP projections from across the primate neocortex and discuss new data which are required to improve the utility of anatomical and biophysical models of the human corticosubthalamic system.

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Acknowledgements

This work was supported by a grant from the National Institutes of Health (R01 NS105690).

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National Institutes of Health (R01 NS105690).

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Authors and Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    Clayton S. Bingham & Cameron C. McIntyre

  2. Department of Neurosurgery, Duke University, Durham, NC, USA

    Cameron C. McIntyre

  3. Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark

    Mikkel V. Petersen

  4. Department of Psychiatry and Neuroscience, Laval University, Quebec, Canada

    Martin Parent

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  1. Clayton S. Bingham
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  2. Mikkel V. Petersen
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  4. Cameron C. McIntyre
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Conceptualization: CSB, MVP, MP, CCM; Methodology: CSB, CCM; Writing-original draft: CSB; Writing/Editing: CSB, CCM, MVP, MP; Funding acquisition: CCM; Resources: CCM.

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Correspondence to Cameron C. McIntyre.

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CCM is a paid consultant for Boston Scientific Neuromodulation, receives royalties from Hologram Consultants, Neuros Medical, Qr8 Health, and is a shareholder in the following companies: Hologram Consultants, BrainDynamics, Surgical Information Sciences, CereGate, Autonomic Technologies, Cardionomic, Enspire DBS.

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Bingham, C.S., Petersen, M.V., Parent, M. et al. Evolving characterization of the human hyperdirect pathway. Brain Struct Funct 228, 353–365 (2023). https://doi.org/10.1007/s00429-023-02610-5

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