A neurocomputational view of the effects of Parkinson's disease on speech production.

The purpose of this article is to review the scientific literature concerning speech in Parkinson's disease (PD) with reference to the DIVA/GODIVA neurocomputational modeling framework. Within this theoretical view, the basal ganglia (BG) contribute to several different aspects of speech motor learning and execution. First, the BG are posited to play a role in the initiation and scaling of speech movements. Within the DIVA/GODIVA framework, initiation and scaling are carried out by initiation map nodes in the supplementary motor area acting in concert with the BG. Reduced support of the initiation map from the BG in PD would result in reduced movement intensity as well as susceptibility to early termination of movement. A second proposed role concerns the learning of common speech sequences, such as phoneme sequences comprising words; this view receives support from the animal literature as well as studies identifying speech sequence learning deficits in PD. Third, the BG may play a role in the temporary buffering and sequencing of longer speech utterances such as phrases during conversational speech. Although the literature does not support a critical role for the BG in representing sequence order (since incorrectly ordered speech is not characteristic of PD), the BG are posited to contribute to the scaling of individual movements in the sequence, including increasing movement intensity for emphatic stress on key words. Therapeutic interventions for PD have inconsistent effects on speech. In contrast to dopaminergic treatments, which typically either leave speech unchanged or lead to minor improvements, deep brain stimulation (DBS) can degrade speech in some cases and improve it in others. However, cases of degradation may be due to unintended stimulation of efferent motor projections to the speech articulators. Findings of spared speech after bilateral pallidotomy appear to indicate that any role played by the BG in adult speech must be supplementary rather than mandatory, with the sequential order of well-learned sequences apparently represented elsewhere (e.g., in cortico-cortical projections).

Premotor cortex is hypoactive during sustained vowel production in individuals with Parkinson's disease and hypophonia.

Introduction: Hypophonia is a common feature of Parkinson's disease (PD); however, the contribution of motor cortical activity to reduced phonatory scaling in PD is still not clear. Methods: In this study, we employed a sustained vowel production task during functional magnetic resonance imaging to compare brain activity between individuals with PD and hypophonia and an older healthy control (OHC) group. Results: When comparing vowel production versus rest, the PD group showed fewer regions with significant BOLD activity compared to OHCs. Within the motor cortices, both OHC and PD groups showed bilateral activation of the laryngeal/phonatory area (LPA) of the primary motor cortex as well as activation of the supplementary motor area. The OHC group also recruited additional activity in the bilateral trunk motor area and right dorsal premotor cortex (PMd). A voxel-wise comparison of PD and HC groups showed that activity in right PMd was significantly lower in the PD group compared to OHC (p < 0.001, uncorrected). Right PMd activity was positively correlated with maximum phonation time in the PD group and negatively correlated with perceptual severity ratings of loudness and pitch. Discussion: Our findings suggest that hypoactivation of PMd may be associated with abnormal phonatory control in PD.

The effects of a simulated fMRI environment on voice intensity in individuals with Parkinson's disease hypophonia and older healthy adults.

PURPOSE: Functional magnetic resonance imaging (fMRI) has promise for understanding neural mechanisms of neurogenic speech and voice disorders. However, performing vocal tasks within the fMRI environment may not always be analogous to performance outside of the scanner. Using a mock MRI scanner, this study examines the effects of a simulated scanning environment on vowel intensity in individuals with Parkinson's disease (PD) and hypophonia and older healthy control (OHC) participants. METHOD: Thirty participants (15 PD, 15 OHC) performed a sustained /ɑ/ vowel production task in three conditions: 1) Upright, 2) Mock Scanner + No Noise, and 3) Mock Scanner + MRI noise. We used a linear mixed-effects (multi-level) model to evaluate the contributions of group and recording environment to vowel intensity. A second linear mixed-effects model was also used to evaluate the contributions of PD medication state (On vs. Off) to voice intensity. RESULTS: Vowel intensity was significantly lower for PD compared to the OHC group. The intensity of vowels produced in the Upright condition was significantly lower compared to the Mock Scanner + No Noise condition, while vowel intensity in the Mock Scanner + MRI Noise condition was significantly higher compared to the Mock Scanner + No Noise condition. A group by condition interaction also indicated that the addition of scanner noise had a greater impact on the PD group. A second analysis conducted within the PD group showed no effects of medication state on vowel intensity. CONCLUSION: Our findings demonstrate that performance on voice production tasks is altered for PD and OHC groups when translated into the fMRI environment, even in the absence of acoustic scanner noise. For fMRI studies of voice in PD hypophonia, careful thought should be given to how the presence of acoustic noise may differentially affect PD and OHC, for both group and task comparisons.

Altered resting-state functional connectivity of the putamen and internal globus pallidus is related to speech impairment in Parkinson's disease.

INTRODUCTION: Speech impairment in Parkinson's disease (PD) is pervasive, with life-impacting consequences. Yet, little is known about how functional connections between the basal ganglia and cortex relate to PD speech impairment (PDSI). Whole-brain resting-state connectivity analyses of basal ganglia nuclei can expand the understanding of PDSI pathophysiology. METHODS: Resting-state data from 89 right-handed subjects were downloaded from the Parkinson's Progression Markers Initiative database. Subjects included 12 older healthy controls ("OHC"), 42 PD patients without speech impairment ("PDN"), and 35 PD subjects with speech impairment ("PDSI"). Subjects were assigned to PDN and PDSI groups based on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III speech item scores ("0" vs. "1-4"). Whole-brain functional connectivity was calculated for four basal ganglia seeds in each hemisphere: putamen, caudate, external globus pallidus (GPe), and internal globus pallidus (GPi). For each seed region, group-averaged connectivity maps were compared among OHC, PDN, and PDSI groups using a multivariate ANCOVA controlling for the effects of age and sex. Subsequent planned pairwise t-tests were performed to determine differences between the three groups using a voxel-wise threshold of p < 0.001 and cluster-extent threshold of 272 mm3 (FWE<0.05). RESULTS: In comparison with OHCs, both PDN and PDSI groups demonstrated significant differences in cortical connectivity with bilateral putamen, bilateral GPe, and right caudate. Compared to the PDN group, the PDSI subjects demonstrated significant differences in cortical connectivity with left putamen and left GPi. PDSI subjects had lower connectivity between the left putamen and left superior temporal gyrus compared to PDN. In addition, PDSI subjects had greater connectivity between left GPi and three cortical regions: left dorsal premotor/laryngeal motor cortex, left angular gyrus, and right angular gyrus. CONCLUSIONS: The present findings suggest that speech impairment in PD is associated with altered cortical connectivity with left putamen and left GPi.

Connectivity of the subthalamic nucleus and globus pallidus pars interna to regions within the speech network: a meta-analytic connectivity study.

Cortico-basal ganglia connections are involved in a range of behaviors within motor, cognitive, and emotional domains; however, the whole-brain functional connections of individual nuclei are poorly understood in humans. The first aim of this study was to characterize and compare the connectivity of the subthalamic nucleus (STN) and globus pallidus pars interna (GPi) using meta-analytic connectivity modeling. Structure-based activation likelihood estimation meta-analyses were performed for STN and GPi seeds using archived functional imaging coordinates from the BrainMap database. Both regions coactivated with caudate, putamen, thalamus, STN, GPi, and GPe, SMA, IFG, and insula. Contrast analyses also revealed coactivation differences within SMA, IFG, insula, and premotor cortex. The second aim of this study was to examine the degree of overlap between the connectivity maps derived for STN and GPi and a functional activation map representing the speech network. To do this, we examined the intersection of coactivation maps and their respective contrasts (STN > GPi and GPi > STN) with a coordinate-based meta-analysis of speech function. In conjunction with the speech map, both STN and GPi coactivation maps revealed overlap in the anterior insula with GPi map additionally showing overlap in the supplementary motor area (SMA). Among cortical regions activated by speech tasks, STN was found to have stronger connectivity than GPi with regions involved in cognitive linguistic processes (pre-SMA, dorsal anterior insula, and inferior frontal gyrus), while GPi demonstrated stronger connectivity to regions involved in motor speech processes (middle insula, SMA, and premotor cortex).

Understanding the neural mechanisms involved in sensory control of voice production.

Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0.