Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation

Abstract

Atypical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). "Neurally impaired" versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable's motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit.

Keywords: Basal ganglia; Brain imaging; Dopamine; Neural modeling; Speech fluency; Speech motor control; Stuttering; Thalamus; Ventral premotor cortex; White matter.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Fig. 1

“Box-and-arrow” schematic of the extended GODIVA model and its integration with the DIVA model. Although these models utilize feedback control, only the feedforward control portion of the model is shown because it is focal in this paper’s simulations of stuttering. The input to the model is the word “godiva”. GPi = internal globus pallidus. GPe = external globus pallidus. For simplicity, details of the model’s representation of the presupplementary motor area, and the projection from the vPMC planning layer to the thalamus, are omitted.

Fig. 2

Idealized circuitry of the basal ganglia - ventral premotor cortex (BG-vPMC) loop. The cells of the circuit are represented by squares. Inside each square is the GODIVA model’s variable that codes for the cell’s activation level (see Section 1 of the Supplementary material for relevant equations). The model treats the cortico-striatal-pallidal-thalamic projections as a set of competitive channels. Two of these are included in the diagram and coded by an orange or a blue box for each cell type within the channel: one channel is for the well-learned syllable “go” (orange squares; variables with subscript 1), and the other channel is for the well-learned syllable “di” (blue squares; variables with subscript 2). Within each channel are two striatal projection neuron cells: a putamen D1R cell of the direct pathway, shown projecting to GPi/SNr, and a putamen D2R cell of the indirect pathway, shown projecting to GPe. Also shown for each channel are: one striatal GABAergic interneuron cell (putamen IN cell) shown as a mediator of feedforward inhibition, one internal pallidum cell (GPi/SNr), one external pallidum cell (GPe), and one thalamic cell. The cortical columns are shown as well, each represented by one SSM plan cell at the vPMC planning layer, and one SSM choice cell at the vPMC choice layer. The projections from the vPMC planning layer to the thalamus are omitted for simplicity. The deep-layer motor cells of the vMC, as well as their afferents (from the vPMC choice layer) and efferents (to the brainstem), are shown on the right. The corticostriatal white matter fibers that arise from the vMC’s efferents, feed into a stage (not modeled as a single cell, but algorithmically, so depicted as a triangle) that detects imminent syllable completion. This stage outputs a transient syllable-completion signal to the putamen D2R cells.

Fig. 3

The state of the basal ganglia - ventral premotor cortex (BG-vPMC) loop at two consecutive stages in the selection of the motor program adequate for the syllable “go”: (a) differential activation of the SSM plan and choice cells, (b) activation of the direct pathway biases cortical competition in favor of “go” SSM choice cell which reads out the motor program for “go”. The height of the bars represents cell activation level, and the thickness of the arrows represents strength of excitation/inhibition. Cortical and thalamic thresholds are marked by dashed lines. The rest of the conventions are as in Fig. 2. In each panel, the green dashed arrows indicate the excitatory or inhibitory signals that drive the circuit into the next stage. Only the relevant subset of the circuit is presented: the direct pathway, the GPi, the thalamus, and the vPMC.

Fig. 4

The state of the basal ganglia - ventral premotor cortex (BG-vPMC) loop and its projections to the motor cortex at three consecutive stages in the shift from the “go” to the “di” syllables: (a) execution of the “go” syllable, (b) activation of the indirect pathway when the syllable is about to terminate, (c) quenching of the “go” choice cell paves the way to the execution of the “di” syllable. Conventions are as in Fig. 3. Only the relevant subset of the circuit is presented: the indirect pathway (not in panel c), the GPi, the thalamus, and the vPMC.

Fig. 5

Time course of simulated neural activity in the BG-vPMC loop. The activities of cells that correspond to different well-learned syllables (thus, to different channels and their corresponding cortical columns) are plotted in distinct colors. Shown from top to bottom are SSM plan cells, SSM choice cells, thalamic cells, GPi cells, putamen D1R cells, GPe cells, and putamen D2R cells. For clarity, the thalamic cell activations are shown both in high-pass and full-range views. Motor program execution is shown above the activations of the SSM choice cells. Note that the range of the y-axis varies from plot to plot.

Fig. 6

Time course of neural activities and predicted BOLD responses of the extended GODIVA model with elevated dopamine levels. (a) Neural activities. Conventions as in Fig. 5(b) The BOLD responses predicted by the model for elevated dopamine levels compared with the baseline of normal levels.

Fig. 7

Time course of neural activities and predicted BOLD responses of the extended GODIVA model with structural abnormality in white matter fibers. (a) Neural activities. Conventions as in Fig. 5. (b) The BOLD responses predicted by the model for impaired white matter fibers compared with the baseline of intact fibers.