Methodological considerations for a chronic neural interface with the cuneate nucleus of macaques

Abstract

While the response properties of neurons in the somatosensory nerves and anterior parietal cortex have been extensively studied, little is known about the encoding of tactile and proprioceptive information in the cuneate nucleus (CN) or external cuneate nucleus (ECN), the first recipients of upper limb somatosensory afferent signals. The major challenge in characterizing neural coding in CN/ECN has been to record from these tiny, difficult-to-access brain stem structures. Most previous investigations of CN response properties have been carried out in decerebrate or anesthetized animals, thereby eliminating the well-documented top-down signals from cortex, which likely exert a strong influence on CN responses. Seeking to fill this gap in our understanding of somatosensory processing, we describe an approach to chronically implanting arrays of electrodes in the upper limb representation in the brain stem in primates. First, we describe the topography of CN/ECN in rhesus macaques, including its somatotopic organization and the layout of its submodalities (touch and proprioception). Second, we describe the design of electrode arrays and the implantation strategy to obtain stable recordings. Third, we show sample responses of CN/ECN neurons in brain stem obtained from awake, behaving monkeys. With this method, we are in a position to characterize, for the first time, somatosensory representations in CN and ECN of primates. In primates, the neural basis of touch and of our sense of limb posture and movements has been studied in the peripheral nerves and in somatosensory cortex, but coding in the cuneate and external cuneate nuclei, the first processing stage for these signals in the central nervous system, remains an enigma. We have developed a method to record from these nuclei, thereby paving the way to studying how sensory information from the limb is encoded there.

Neural Basis of Touch and Proprioception in Primate Cortex

“…Not much is known about the response properties of DCN neurons in primates except that they relay sensory information with high temporal fidelity (384). Recent advances in chronic implants will likely lead to insights about neural coding in the DCN (304, 350). …”

Restoring Somatosensation: Advantages and Current Limitations of Targeting the Brainstem Dorsal Column Nuclei Complex

“…Interestingly, despite DCN neurons being somatotopically arranged across the coronal plane of the nuclei, evidence from our laboratory suggests that activity hotspots are spatially displaced across the surface of these nuclei when evoked from different stimulus locations (Loutit et al, 2017(Loutit et al, , 2019a. Recently, Suresh et al (2017) also showed that macaque cuneate somatotopic maps are rostrocaudally organized, in addition to the medial-lateral and dorsal-ventral organization (Loutit et al, 2019b). Accordingly, attempts to stimulate cutaneous upper and lower body regions of the DCN, in addition to proprioceptive regions in the external cuneate nuclei, nuclei X, and nuclei Z, will have to target reasonably spatially displaced areas (Loutit et al, 2019b).…”

“…Congruently, the DCN have received attention as a prospective somatosensory neural prosthetic target. Recently, it was shown that chronically implanted microelectrode arrays in monkeys can collect stable recordings, and variations in electrical DCN stimulation can elicit behavioral responses that demonstrate perceptual discrimination (Richardson et al, 2015(Richardson et al, , 2016Sritharan et al, 2016;Suresh et al, 2017). While these studies establish the DCNc as a potential target, there is a severe lack of fundamental knowledge of the DCNc functional organization and somatosensory signal processing, which needs to be addressed before this region can be pursued as a feasible neural prosthetic target.…”

Mechanical vibration does not systematically reduce the tremor in Essential Tremor patients

“…Given the potentially important role of descending cortical input on cuneate activity 48 , it is perhaps not surprising if the influence of mechanoreceptors is not what would be expected based on those studies. A second potential confound to test our hypothesis is that the neuroanatomy of the primate cuneate nucleus seems to differ from that of the cat 49 . Therefore, additional neurophysiological studies are needed to better understand the neural pathways involved in the generation of ET and how to target them for new interventions.…”