Electrophysiological characterization of the hyperdirect pathway and its functional relevance for subthalamic deep brain stimulation

Bahne H. Bahners, Gunnar Waterstraat, Silja Kannenberg, Gabriel Curio, Alfons Schnitzler, Vadim Nikulin, Esther Florin
Exp Neurol.


The subthalamic nucleus (STN) receives input from various cortical areas via hyperdirect pathway (HDP) which bypasses the basal-ganglia loop. Recently, the HDP has gained increasing interest, because of its relevance for STN deep brain stimulation (DBS). To understand the HDP’s role cortical responses evoked by STN-DBS have been investigated. These responses have short (<2 ms), medium (2-15 ms), and long (20-70 ms) latencies. Medium-latency responses are supposed to represent antidromic cortical activations via HDP. Together with long-latency responses the medium responses can potentially be used as biomarker of DBS efficacy as well as side effects. We here propose that the activation sequence of the cortical evoked responses can be conceptualized as high frequency oscillations (HFO) for signal analysis. HFO might therefore serve as marker for antidromic activation. Using existing knowledge on HFO recordings, this approach allows data analyses and physiological modeling to advance the pathophysiological understanding of cortical DBS-evoked high-frequency activity.

Published: 2022 Mar

Figure 1

Medium-latency evoked cortical responses (eCR) (top left, orange) result from hyperdirect pathway (HDP, orange fibers) activation. Short-latency eCR (top right, green) originate from corticospinal tract (CST, green fibers) activation. Orange and green eCR example traces are schematic drawings that do not refer to any particular recording modality. Example electrode trajectories inside the subthalamic nucleus (STN) and cortical surface were visualized using Lead-DBS (lead-dbs.org, RRID:SCR_002915) (Horn and Kühn, 2015). Subsections of the STN colored in orange (motor), blue (associative) and yellow (limbic) as well as fiber tracts of HDP (orange) and CST (green) were visualized with subcortical atlases pre-installed in Lead-DBS (Ewert et al., 2018Meola et al., 2016Middlebrooks et al., 2020). All structures are overlaid an axial section of the BigBrain dataset (Amunts et al., 2013) at z = −12 mm. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)