Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement

Abstract

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production

“…A smaller proportion (15%) of decrease-type responses were locked to speech production onset, with remaining responses not clearly associated with either event. Altought minority populations of neurons with movement-related firing-rate decreases have been reported previously (Wichmann et al, 1994;Schrock et al, 2009;Lipski et al, 2017), and active movements have been associated with a higher proportion of decrease-type responses in the STN (Lipski et al, 2017), it is remarkable that such a high percentage of decrease-type responses were observed in the present study. Interestingly, and in contrast to our results, a marked reduction of STN activity was reported to be associated with the onset of speech production in the only previous report of STN unit activity recorded during speech production (Watson and Montgomery, 2006), although that study was largely descriptive in nature, limiting comparisons to our data.…”

Subthalamic nucleus and sensorimotor cortex activity during speech production

“…In both cases, significant time-frequency modulations emerged about 400 ms before spoken response onset and persisted throughout the execution of speech. Desynchronization of alpha and beta activity and synchronization of high frequency activity have been previously reported as markers of ongoing movement and movement-related patterns in the STN (Androulidakis et al, 2007;Kempf et al, 2007;Lipski et al, 2017;Geng et al, 2018;Lofredi et al, 2018). However, only modulation of beta activity during speech production has been reported (Hebb, Darvas, and Miller, 2012).…”

Local field potentials of subthalamic nucleus contain electrophysiological footprints of motor subtypes of Parkinson’s disease

“…Both couplings showed a similar spatial topography: PAC and spike-phase locking were most pronounced near the superior border of the STN. Interestingly, one recent study also showed that the STN cell firings in PD patients were phase synchronized to both low-and highbeta-frequency cortical oscillations (59). Furthermore, this relationship was not exclusive to motor cortex, as they show the STN firing also demonstrated phase synchronization to both premotor and sensory cortex.…”