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

Abstract

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of 79 unit recordings exhibited firing-rate modulation during a syllable reading task across 12 subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, whereas locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single-syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech.

Keywords: deep-brain stimulation; microelectrode recording; single neuron; speech; subthalamic nucleus.

Copyright © 2018 the authors 0270-6474/18/385620-12$15.00/0.

Figures

Figure 1.

Speech task and representative spoken and neural responses. A, Intraoperative syllable speech task. Subjects were asked to read aloud words presented on a computer screen. Each trial consisted of a sequence beginning with the fixation cross turning green for 250 ms, followed by a variable delay black screen (500–1000 ms), and followed by a unique CVC syllable cue appearing on the screen until the response was recorded. A white fixation cross appeared during the intertrial interval. B, An example audio spectrogram time-aligned to the onset of a subject's utterance of the syllable “loath”. The time (in seconds) of cue presentation is indicated by the solid vertical line, and the response onset and offsets are indicated by dotted lines. C, A single unit recording from the subject's STN, showing an increase in firing during speech. Red hash marks indicate timing of detected spike waveforms from the background activity. D, Overlay of 50 spike waveforms from the single unit shown in C. Scatterplots of the first two principal components (E; principal component1 and principal component2), as well as the first principal component and spike timestamp (F), showing clear separation of single-unit spike waveforms (red) corresponding to the example shown in C from background (blue).

Figure 2.

Schematic illustrating cue- and speech production-locking neuronal response types. A, Hypothetical example of cue-aligned trials, illustrating a constant neuronal response latency with varying speech production latencies. B, Corresponding correlation schematic showing that a significant correlation between neuronal response to production onset interval and speech production latency indicates cue-locking. C, Hypothetical example of cue-aligned trials, illustrating a constant neuronal response to production onset interval with varying speech production latencies. D, Corresponding correlation schematic showing that a significant correlation between the neuronal response latency and speech production latency indicates speech-locking.

Figure 3.

STN neuronal firing is modulated during speech. Examples of A-sort single-unit neuronal responses during speech showing (A) increases, (B) decreases, and (C) mixed responses in firing rate, aligned to production onset (t = 0). Spike rasters across trials are shown in A–C, top, and mean firing rate (A, C) or mean ISI (B) are shown on the bottom. Diamonds labeled with a “c” indicate mean time of cue presentation; diamonds labeled with an “e” indicate mean speech end; dashed error bars indicate the corresponding SDs. D–F, Raster plots illustrating the timing of firing rate responses across the population of unit recordings. Each row represents a unit's significant changes relative to baseline, during a time segment surrounding production onset. The time scale is normalized across units from 0.5 s before the mean cue onset until 0.5 s after the mean end of speech.

Figure 4.

STN neuronal firing increases are primarily speech-locked. A, An example of an A-sort single unit whose firing rate increase is locked to production onset. Spike raster (top) and mean firing rate (bottom) aligned to cue presentation. Significant spike bursts are shaded for each trial according to their PS index. Trials are sorted by speech production latency; speech production onset for each trial is indicated in green. B, The time interval between cue presentation and burst onset (neuronal response latency) and between burst onset and production onset (neuronal response to production interval) for each trial is correlated against production latency. C, Summary of correlation analyses for all unit recordings with increase-type responses, showing 12/29 responses locked to production onset (red circles), 2/29 responses locked to cue presentation (blue circles), and 2/29 responses locked to both cue and production onset (black circles). Open circles in C and indicate B-sorts.

Figure 5.

STN neuronal firing decreases are primarily cue-locked. A, An example of an A-sort multi-unit whose firing rate decrease is locked to cue presentation. Spike raster (top) and mean firing rate (bottom) aligned to cue presentation. Significant decreases in firing rate (pauses) are shaded for each trial according to their PS index. Trials are sorted by speech production latency; speech production onset for each trial is indicated in green. B, The time interval between cue presentation and pause onset (neuronal response latency) and between pause onset and production onset (neuronal response to production interval) for each trial is correlated against production latency. C, Summary of correlation analyses for all unit recordings with inhibitory responses, showing 3/20 responses were locked to production onset (red circles), 8/20 units were locked to cue presentation (blue circles), and none locked to both cue presentation and production onset (black circles). Open circles in C and indicate B-sorts.

Figure 6.

Anatomical distribution of speech responses in the STN. Unit locations are represented according to the recording trajectory and recording depth relative to electrophysiology-defined STN boundaries (0% corresponds to the ventral STN border and 100% corresponds to the dorsal STN border. Box plots represent the median and IQR of recording depths within each response category. NR = no response.

Figure 7.

Anatomical distribution of STN microelectrode unit recordings in MNI space. A, Speech-related unit response types and (B) locking types were not segregated in normalized anatomical coordinates.