First evidence of a hyperdirect prefrontal pathway in the primate: precise organization for new insights on subthalamic nucleus functions

Abstract

The direct connections from the cortex to the subthalamic nucleus (STN), the so-called hyperdirect pathway, is known for the cortical motor areas and plays a top–down executive control on basal ganglia (BG). However, little was known regarding the projections onto the STN from anterior and ventral prefrontal regions involved in more integrated functions such as decision making or reward related processes. The large-scale study by Haynes and Haber aimed to trace the hyperdirect pathway from different territories of the prefrontal cortex and motor areas to determine the levels of convergence and segregation of these projections onto the different subterritories of the STN. Their first objective was to delineate all frontal inputs to the STN in monkeys, extending to primate those already described in rodents (Berendse and Groenewegen, 1991). They impressively targeted many areas constitutive of four prefrontal regions: ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), dorsal anterior cingulate cortex (dACC) and dorsal prefrontal cortex (dPFC), and established that all of them project onto the STN. These cortices are differentially involved in cognitive, motivational and emotional processes. Do these distinct information funnel in the STN or remain processed separately by STN subterritories? The second objective was to delineate a limbic STN based on the topography of the projections from areas of the vmPFC, OFC, and dACC, involved in reward-related processes. The authors mapped the limbic part of the STN from the medial tip of the nucleus to the lateral part of the LH. However, since not all areas from the vmPFC and OFC and other limbic cortices have been investigated, the study does not allow to assess the exact extent of this limbic STN. Finally, the authors examined the convergence and/or segregation of cortico-STN fibers from motor, cognitive and limbic cortical areas. The central part of the STN receives overlapping projections from the majority of labeled cortical afferences. However, motor projections to the dorsal lateral extremities seem to be isolated from those forming the limbic territories, located at the medial tip of the nucleus.