A motor speech disorder or dysarthria is found in 70%–90% of patients with Parkinson’s disease (PD),1–3 negatively impacting quality of life.4,5 Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal motor symptoms of PD.6 While acoustic measures and lip force may improve with DBS, most studies have reported either no improvement or a decline in motor speech production.3,7–10 The decline is pronounced at higher stimulation settings and is attributed to the spread of current to nearby pathways.9,11 Medially placed left electrodes, longer disease duration, and more impaired speech clarity prior to surgery have been reported to underlie motor speech deterioration after STN DBS.12,13 Stimulation of the left anterior sensorimotor STN has been reported to be associated with improved voice function.14 The motor speech changes after STN DBS have been reported to be variable and multifactorial.13 Predicting which patients are most likely to experience postoperative motor speech worsening could help to inform patient expectations and management.
At our center, all patients treated with STN DBS are consistently evaluated by a certified speech pathologist preoperatively during the selection process, intraoperatively during lead placement, and postoperatively after programming settings have stabilized. Our experience creates an opportunity to study the motor speech effects of STN DBS prospectively and in detail. The work herein has three aims. First, we examined the types and prevalence of motor speech changes observed with STN DBS and related them to the preoperative condition. Second, we examined the ability of intraoperative testing to predict postoperative changes in motor speech. Third, we examined the spatial relationship between stimulation sites producing maximal motor improvement, as measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and maximal motor speech deterioration.
Methods
Patient Population and Informed Consent
This study included consecutive patients with advanced idiopathic PD who underwent STN DBS surgery at our institution from 2011 to 2016. DBS candidates had an established diagnosis of PD with motor fluctuations despite optimal medical management or severe, medically refractory rest tremor. Patients were not offered surgery if they had dementia, severe psychiatric symptoms, structural brain abnormalities, or other medical contraindications. Our detailed selection criteria for STN DBS have been previously published.15–17 All subjects signed written informed consent. The study was approved by the University of Michigan Medical Institutional Review Board.
DBS Surgical Procedure
Prior to surgery, all patients underwent 3-T MRI utilizing a validated imaging protocol to visualize the STN.17–19 The DBS procedure occurred in two stages. Stage I surgery involved bilateral implantation of STN DBS electrodes (model 3389, Medtronic Inc.) with microelectrode recording. The procedure was performed with the patient awake, under local anesthesia without sedation. During surgery, a movement disorders neurologist and a speech pathologist conducted monopolar review of electrode contacts on each side to document symptom improvements and side-effect thresholds. The right side was operated on first. Stage II surgery to implant the pulse generator occurred 2–4 weeks after stage I. A high-resolution CT scan18 was obtained to visualize individual DBS contacts at this time since brain shift and intracranial air had resolved. DBS programming occurred 4–6 weeks after initial lead placement. Postoperative DBS programming was performed independently and blinded to motor speech evaluation results.
Motor Speech/Dysarthria Evaluation
In this study, the same speech pathologist (K.J.K.) with 40 years of clinical experience evaluating patients with neurological disorders conducted motor speech evaluations during preoperative evaluation, during awake DBS surgery, and following optimized DBS programming and medication adjustment. Because dopaminergic medications improve motor symptoms without significantly affecting speech,20 and to minimize off-medication patient discomfort, preoperative motor speech evaluations were performed in the on-medication state and postoperative motor speech evaluations were performed in the on-medication/on-stimulation state. Intraoperative motor speech evaluations were performed in the off-medication state, off and on stimulation. Medication and DBS stimulation parameters were stable at least 1 month before the postoperative speech pathology evaluation.
Comprehensive preoperative and postoperative motor speech evaluations took place individually in a quiet room and included standard assessment of cranial nerve/oral motor function of head/neck control, face, jaw, tongue, soft palate, and respiration at rest and during movement.21 Oral agility was assessed by the administration of the oral diadochokinetic rates of “pa,” “ta,” “ka,” and “pataka”21 and nonverbal agility (number of rapidly repeated voluntary lip/face, jaw, and tongue movements in 5 seconds, total number of points = 12) and verbal agility (number of repetitions of multisyllabic words in 5 seconds, total number of points = 14) subtests from the Boston Diagnostic Aphasia Examination (BDAE).22 Because motor speech processes of voice, resonance, articulation, and prosody can be different across speaking tasks,11,21,23 deviant motor speech dimensions were identified by perceptual analysis of voice, resonance, articulation, and prosody during a variety of speaking tasks, including spontaneous speech, picture description (“Cookie Theft” picture from the BDAE), oral reading of the “Grandfather Passage” (text used by Darley et al.23 that includes nearly all phonemes of American English), reciting the alphabet, repetition of multisyllabic words or BDAE verbal agility subtest, oral diadochokinetic rates, and sustaining the vowel sounds “ah” and “eee” for as long as possible. We used the 35 deviant motor speech dimensions and definitions of deviant motor speech dimensions as given by Darley et al.23 For diagnosis of the type of dysarthria, we used the University of Michigan Classification of Hypokinetic Dysarthria, University of Michigan Classification of Spastic Dysarthria, and the Mayo Clinic Classification of Dystonic Dysarthria.23,24 Speech intelligibility is dependent on a combination of motor speech components, and the overall dysarthria rating (DR) was scored from 0 (normal intelligibility) to 7 (anarthria; see Supplementary Table 1). All motor speech samples were recorded.
During surgery to obtain the off-medication intraoperative baseline, brief cranial nerve/oral motor, motor speech, and language examinations were performed prior to DBS lead insertion. After lead placement, monopolar review was performed at a pulse width of 60 µsec, frequency of 130 Hz, and stimulation amplitude from 0 to 5 V at 0.5-V increments, to observable and undesirable side effects. Perceptual analysis of the motor speech processes of voice, resonance, articulation, and prosody (spontaneous speech, reciting automatized sequences, repetition of multisyllabic words) was performed throughout electrode testing along with close monitoring of the patient’s face and perioral region. The lowest stimulation amplitude and deviant motor speech dimensions identified were recorded with a severity rating assigned. Effects of right- and left-sided stimulation were evaluated separately.
Site of Stimulation Determination
To identify stimulation sites for optimal postoperative motor improvement and worsened dysarthria, we utilized our previously described atlas-independent, fully individualized, computational electrical field approach, integrating anatomical, clinical, and electrophysiological information.17,25 For each patient, coordinates of the DBS active contact were obtained from postoperative CT imaging. A mutual-information algorithm was used to coregister the preoperative 3-T MR image to the postoperative CT (Analyze, AnalyzeDirect Inc.), allowing coordinate locations to be defined with respect to the anatomical midpoint of the MRI-visualized STN.17,18 For each point in space, we calculated a weighted score equal to the sum over all active contacts of motor improvement (MDS-UPDRS Part III [MDS-UPDRSIII]) or DR change, respectively, multiplied by the probability that a given contact at the stimulation amplitude would activate a neuron at that specific spatial location. To minimize bias, MDS-UPDRS and DR scores for a given patient applied equally to both leads. A simplex algorithm and bootstrapping (MATLAB, MathWorks Inc.) were used to identify and statistically distinguish the spatial mean locations associated with the sites of maximal effect (for additional methodological detail, see Conrad et al.17 and Mossner et al.25).
Statistical Analysis
Statistical analysis was performed using RStudio (version 1.1.456). All distances are reported in millimeters. Results are expressed as the mean ± standard deviation unless otherwise noted. A p value of less than 0.05 was considered significant. Wilcoxon signed-rank tests were used to determine if the postoperative motor speech assessments of verbal agility, nonverbal agility, and DR significantly differed from preoperative assessments for the whole cohort. Chi-square analysis was used to measure the significance of relationships between categorical variables.
Results
Demographics and STN DBS Motor Outcomes
Our study included 43 PD patients (31 men, 12 women) who underwent bilateral STN DBS. The mean age at preoperative evaluation (within 6 months of surgery) was 63 ± 7.2 years (range 41–73 years) with a disease duration of 9.4 ± 5.2 years. The mean age at postoperative follow-up was 64 ± 6.9 years. Preoperative MDS-UPDRSIII motor scores were 42 ± 15 off medication and 22 ± 10 on medication. Postoperative MDS-UPDRSIII motor scores were 49 ± 17 off medication/off stimulation, 32 ± 15 off medication/on stimulation, and 22 ± 10 on medication/on stimulation. The levodopa equivalent dose was reduced from 1400 ± 870 mg to 720 ± 540 mg between preoperative and postoperative evaluations.
Motor Speech Assessment
All patients had a masked face with infrequent eye blinking prior to and after DBS surgery. Two patients had no dysarthria prior to surgery, but all patients had dysarthria after surgery. No patients displayed dysfluencies/stuttering before or after surgery. Nonverbal agility skills (8.7 ± 1.9 vs 8.6 ± 1.8, respectively, p = 0.64) and verbal agility skills (14 ± 0.6 vs 14 ± 1.4, respectively, p = 0.14) did not significantly change from pre- to postoperative evaluations. By contrast, mean DR scores worsened significantly, from 2.2 ± 1.2 (mild impairment) to 2.7 ± 1.1 (mild-moderate impairment; p = 0.0003). For individuals, DRs were unchanged in 26 (60%) of 43 patients, improved by 1 level in 1 (2%) of 43 patients, and declined by 1 level in 16 (37%) of 43 patients.
Predicting Motor Speech Worsening From Preoperative Dysarthria Type
The relationship between preoperative dysarthria type and postoperative DR worsening is summarized in Table 1. Hypokinetic dysarthria components were most common, as expected in PD patients.2 A total of 39 (91%) of the 43 patients had some hypokinetic components. A mixed hypokinetic-dystonic dysarthria was found in 20 (47%) of 43 patients. Of these 20 patients, 8 (40%) experienced a worsened DR, a higher percentage than in the hypokinetic-only dysarthria group (2 [13%] of 15). Even so, hypokinetic-dystonic dysarthria was neither predictive nor protective for DR worsening (χ2 = 1.68, p = 0.19). Three groups (hypokinetic-dystonic-spastic, dystonic only, and no dysarthria) had DR worsening in all members; however, these dysarthria types occurred too infrequently (only 5 [12%] of 43 patients) to reach statistical significance.
Distribution of dysarthria component types and postoperative DR worsening
| Preop Dysarthria Type | No. (%) | |
|---|---|---|
| Prevalence | Postop DR Worsening | |
| Hypokinetic only | 15/43 (35) | 2/15 (13) |
| Mixed hypokinetic-dystonic | 20/43 (47) | 8/20 (40) |
| Mixed hypokinetic-spastic | 3/43 (7) | 1/3 (33) |
| Mixed hypokinetic-dystonic-spastic | 1/43 (2) | 1/1 (100) |
| Dystonic only | 2/43 (5) | 2/2 (100) |
| Spastic only | 0/43 (0) | 0/0 (0) |
| Mixed dystonic-spastic | 0/43 (0) | 0/0 (0) |
| None | 2/43 (5) | 2/2 (100) |
Predicting Motor Speech Outcome From Intraoperative Testing
The association between intraoperative testing outcomes and postoperative DR is summarized in Table 2. Among 16 (37%) of 43 patients with worsened DR at follow-up, 11 (69%) had demonstrated increased dysarthria (either-sided stimulation) intraoperatively and 5 (31%) had not, a difference that reached statistical significance (χ2 = 5.1, p = 0.02). During right-sided stimulation, 9 (56%) of the 16 patients had demonstrated dysarthria worsening intraoperatively and 7 (44%) had not, a difference that did not reach statistical significance (χ2 = 2.97, p = 0.08). In contrast, for left-sided stimulation, 11 (69%) of the 16 had demonstrated increased dysarthria intraoperatively and 5 (31%) had not, a difference that reached statistical significance (χ2 = 5.1, p = 0.02). The odds of postoperative DR worsening were 4.4 times higher for STN DBS patients who had experienced worsened dysarthria during intraoperative testing (for either-sided or left-sided stimulation) than those who had not worsened intraoperatively (p = 0.02).
Intraoperative testing predicts postoperative dysarthria worsening
| Intraop Testing | Worsening w/ Rt Lead | Worsening w/ Lt Lead |
|---|---|---|
| Sensitivity | 56% | 69% |
| Specificity | 70% | 67% |
| Positive predictive value | 53% | 55% |
| Negative predictive value | 73% | 78% |
| Odds ratio | 3.05 | 4.40 |
| Chi-square test | ||
| χ2 | 2.97 | 5.06 |
| p value | 0.08 | 0.02 |
Next, we examined the amplitudes and locations of stimulation that produced dysarthria during intraoperative stimulation. Among the 17 patients with worsening dysarthria during right-sided stimulation, the lowest amplitude of stimulation producing worsening dysarthria was 3.96 ± 0.79 V in 49 electrode contacts. Among the 20 patients with worsening dysarthria during left-sided stimulation, the lowest amplitude of stimulation producing worsening dysarthria was 3.67 ± 0.95 V in 60 electrode contacts. The amplitude difference between right and left sides was not statistically significant (p = 0.09). On the left, the minimum amplitude to produce worsening dysarthria was significantly lower for the ventral-most contact (3.53 ± 0.22 V) than the dorsal-most contact (4.00 ± 0.22 V, p < 0.0001). On the right, there was no statistically significant difference between the ventral-most (3.83 ± 0.27 V) and dorsal-most contacts (3.90 ± 0.23 V, p = 0.53). Hence, intraoperative worsening of dysarthria during left-sided stimulation occurs at a somewhat lower amplitude in the ventral-most contact than in the dorsal-most contact.
Stimulation Loci for Optimal Motor Improvement and Worsened Dysarthria
Optimal motor outcomes in STN DBS are typically expected with dorsolateral stimulation, whereas worsened dysarthria is associated with stimulation spread to corticobulbar tracts in the internal capsule. Our data provided an opportunity to test this hypothesis in detail. We expected the sites of stimulation-associated optimal motor improvement (MDS-UPDRSIII) to be distinct from those producing worsened dysarthria (DR). We localized regions of maximal effect in an atlas-independent and fully individualized manner relative to the MRI-visualized STN midpoint, for overall MDS-UPDRSIII outcomes and postoperative dysarthria (Table 3). For this analysis, 10 patients (20 leads) were excluded because of incomplete imaging or DBS programming data. Maximal MDS-UPDRS motor improvement occurred with stimulation 0.09 mm lateral, 0.93 mm posterior, and 1.75 mm dorsal to the STN midpoint, consistent with our previous findings.17 By contrast, maximally worsened dysarthria occurred with stimulation 0.12 mm anterior and 1.4 mm ventral to the MRI-visualized STN midpoint. Differences in stimulation location for motor improvements and dysarthria worsening were statistically significant.
Site locations of maximal DR worsening and MDS-UPDRSIII total improvement, relative to the STN midpoint
| Outcome Measure | X (lateral) | Y (posterior) | Z (dorsal) |
|---|---|---|---|
| Worsened DR (95% CI) | 0.12 (−0.87 to 1.1) | −0.12 (−0.63 to 0.53) | −1.4 (−2.3 to −0.17) |
| MDS-UPDRSIII total (95% CI) | 0.09 (−0.22 to 0.43) | 0.93 (0.44 to 1.39) | 1.75 (1.3 to 2.2) |
Values are expressed in millimeters.
To illustrate sites of optimal motor improvement and maximally worsened dysarthria with respect to STN regional anatomy, we show these two sites for average-sized volumes of tissue activation in Fig. 1. As illustrated in the figure, the site of optimal motor stimulation is dorsal and posterior to the STN midpoint, in the motor region of the STN. By contrast, the site of maximal dysarthria worsening is anterior and ventral, with significant overlap with passing corticobulbar fibers in the internal capsule. The separation between volumes of tissue activation for optimal MDS-UPDRS motor improvement and worsened DR outcomes introduces the possibility for directional reprogramming or repositioning of electrodes to improve dysarthria without sacrificing overall motor benefits in patients experiencing worsened DR.
Distinct stimulation sites for dysarthria and motor improvement. Average volumes of tissue activation for maximal MDS-UPDRS motor improvement (green) and dysarthria worsening (red). DBS electrode shown with the STN (yellow), substantia nigra (purple), and internal capsule (blue fibers). A = anterior; D = dorsal; L = lateral. Figure is available in color online only.
Discussion
Motor speech disorder or dysarthria is common among patients with PD and can occur following STN DBS surgery, negatively impacting quality of life. In our cohort, 16 of 43 patients experienced postoperative worsening of their motor speech despite MDS-UPDRS improvement. STN DBS negatively impacted dysarthria, but not verbal or nonverbal agility skills. The presence of worsened motor speech concurrent with improved PD motor symptoms is not surprising. STN DBS programming is adjusted to optimize motor effects on the extremities, sometimes neglecting the possibility of different effects on motor speech production.2
Predicting which patients are most likely to experience post-DBS motor dysarthria could help to inform patient expectations and management. We found that, while baseline dysarthria characteristics are not predictive of postoperative worsening, intraoperative motor speech testing strongly predicts postoperative worsening and that stimulation sites for motor improvement and dysarthria worsening are distinct. Our findings indicate the potential to minimize stimulation-induced dysarthria through intraoperative electrode repositioning or postoperative directional tuning.
These findings are readily translatable to everyday patient care. The preoperative and postoperative assessments occurred in the clinical setting during routine patient visits. The on-medication preoperative evaluation provided realistic clinical information regarding the deviant motor speech dimensions identified, dysarthria type, and dysarthria severity. All preoperative and postoperative motor speech evaluations were performed with medications and/or the DBS system set to achieve maximal nonspeech motor benefit to the patient. One resulting limitation of this approach is that dopaminergic medication effects on dysarthria were not measured. However, these effects may be small.2,20 As another limitation, in this clinical setting, the speech pathologist was not blinded to the preoperative, intraoperative, or postoperative condition during the evaluations.
Our work differs from earlier studies of speech with STN DBS in that a certified speech pathologist not only performed comprehensive preoperative and postoperative motor speech testing but was also present during surgery to perform intraoperative motor speech testing at baseline in the operating room and during DBS stimulation. Hence, this is the first study of STN DBS to examine the utility of intraoperative motor speech testing to predict dysarthria outcomes. We estimated the negative and positive predictive values of intraoperative motor speech testing to be 78% and 55%, respectively, for worsening in the left lead or either lead. Interestingly, a significant percentage of patients (45%) who experienced dysarthria worsening intraoperatively did not demonstrate DR worsening at postoperative testing. While a certified speech pathologist may not be available for intraoperative evaluation in all hospitals, this study suggests that the DBS examiner take into account the motor speech dimensions along with the motor symptoms during DBS electrode testing. Transient intraoperative motor speech changes could occur because of multiple factors, ranging from the microlesioning effects of DBS lead placement to fatigue.
We and others have hypothesized that worsening dysarthria may occur because of current spread from DBS leads into the internal capsule with lateral placement26–28 or current spread to cerebellothalamic fibers with medial placement.12,13,29 Still others have suggested that lesions to the basal ganglia caused by the electrode trajectory or levodopa-induced dyskinesias may be responsible for degraded motor speech.30,31 Our study demonstrates for the first time in a quantitative fashion that there is a statistically significant spatial separation between the sites of optimal motor improvement and maximal dysarthria. Our findings suggest that dysarthria arises when stimulation is applied anteroventral to the site of maximal motor improvement. At an average stimulation amplitude, DBS at the site of maximal DR worsening is associated with voltage spread into the internal capsule, whereas the site producing optimal MDS-UPDRSIII improvement does not share this characteristic. Hence, in PD patients with dysarthria after STN DBS, repositioning the DBS electrode or directional programming to stimulate a more posterodorsal location may improve dysarthria without negatively impacting motor outcome.
Our findings are consistent with previously published reports. Tsuboi et al.28 reported several distinct speech and voice changes after STN DBS and noted that stimulation of the corticobulbar and corticospinal tracts caused both dystonic speech changes and strained voice quality from abnormal laryngeal contraction. Tripoliti et al.13 identified more medially placed electrode contacts in the left STN region as a predictive factor for motor speech deterioration. While nonlateralized stimulation of corticobulbar fibers may cause dysarthria, other impairments of communication may be specific to left-sided stimulation medial to the STN. Tripoliti et al.9 reported that a worse preoperative on-medication global motor score was predictive of a postsurgical decline in speech intelligibility; however, there are no established criteria to predict patients at risk for adverse effects of STN DBS on motor speech production.2 Fenoy et al.11 suggested that fibers of the dentatorubrothalamic tract are more often involved in the medially positioned left electrode contacts.
Current spread into pallidofugal and cerebellothalamic fibers, especially for medially placed electrodes, may account for motor speech effects more accurately than spread into corticobulbar pathways. The presence of dystonic components in our study suggests stimulation spread to adjacent pathways such as the cerebellothalamic and corticobulbar tracts. However, specific targeting of the cerebellothalamic fibers in the treatment of essential tremor does not result in significant dysarthria, and these fibers are typically localized posteromedial to the STN midpoint. Fiber tracts located in the anteroventral STN region, which may be within the worsened dysarthria volume of tissue activated, include the corticobulbar, pallidothalamic, and nigrothalamic tracts (for review, see Oishi et al.32).
Finally, Jorge et al.14 examined one feature of motor speech production—voice—and found that left anterior STN stimulation correlated with improvements in voice severity scores and phonatory airflow during spontaneous speech. Our study differs from this work in that we focused on overall speech intelligibility or dysarthria severity, which reflects the combination of the motor speech processes of voice, resonance, articulation, and prosody rather than a single component of motor speech and the relationship to optimal motor improvement.
Conclusions
In summary, this study revealed a subset of patients who experienced deterioration in motor speech following STN DBS surgery and demonstrated that intraoperative testing of motor speech is useful to identify patients at risk for worsened DR after surgery. These patients may benefit from DBS programming that directs the volume of tissue activated to posterodorsal areas that provide more optimal motor improvement without motor speech deterioration.
Acknowledgments
The study was funded by the NIH (4TL1TR000435-10) and a Taubman Medical Research Institute Grand Challenge Award. Dr. Mossner has received research support from a TL1 training grant from the NIH (TL1TR002242). Dr. Chou has received research support from the NIH (NS091856-01, NS10061102, NS107158) and has participated as a site principal investigator in clinical trials sponsored by the Parkinson Study Group (STEADY-PD III, SURE-PD3, NILO-PD). Dr. Patil has received support from the NIH (5R01GM111293-03, 5R01GM098578-08, R01AT010817, 1U01AG057562-01A1, 1U24NS107158-01, 1R01NS105132-01A1), National Science Foundation (1926576), and Taubman Medical Research Institute.
Disclosures
Dr. Chou has participated as a site principal investigator in clinical trials sponsored by Eli Lilly and Voyager Therapeutics; has received royalties from UpToDate and Springer Publishing; and has served as a consultant for Accordant, Boston Scientific, Abbott, and CNS Ratings. Dr. Patil has participated as a site principal investigator in a clinical trial sponsored by Voyager Therapeutics and serves on the Scientific Advisory Board of NeuroOne Medical Technologies, Inc.
Author Contributions
Conception and design: Patil, Kluin, Mossner, Chou. Acquisition of data: all authors. Analysis and interpretation of data: Patil, Kluin, Mossner. Drafting the article: all authors. Critically revising the article: Patil, Kluin, Mossner, Chou. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Patil. Statistical analysis: Patil, Kluin, Mossner. Administrative/technical/material support: Patil, Kluin, Chou. Study supervision: Patil, Kluin, Chou.
Supplemental Information
Online-Only Content
Supplemental material is available with the online version of the article.
Supplementary Table 1. https://thejns.org/doi/suppl/10.3171/2021.12.JNS211729.
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