Long-Term Averaged Spectrum Descriptors of Dysarthria in Patients With Parkinson's Disease Treated With Subthalamic Nucleus Deep Brain Stimulation.

PURPOSE: This study aimed to evaluate whether long-term averaged spectrum (LTAS) descriptors for reading and monologue are suitable to detect worsening of dysarthria in patients with Parkinson's disease (PD) treated with subthalamic nucleus deep brain stimulation (STN-DBS) with potential effect of ON and OFF stimulation conditions and types of connected speech. METHOD: Four spectral moments based on LTAS were computed for monologue and reading passage collected from 23 individuals with PD treated with bilateral STN-DBS and 23 age- and gender-matched healthy controls. Speech performance of patients with PD was compared in ON and OFF STN-DBS conditions. RESULTS: All LTAS spectral moments including mean, standard deviation, skewness, and kurtosis across both monologue and reading passage were able to significantly distinguish between patients with PD in both stimulation conditions and control speakers. The spectral mean was the only LTAS measure sensitive to capture better speech performance in STN-DBS ON, as compared to the STN-DBS OFF stimulation condition (p < .05). Standardized reading passage was more sensitive compared to monologue in detecting dysarthria severity via LTAS descriptors with an area under the curve of up to 0.92 obtained between PD and control groups. CONCLUSIONS: Our findings confirmed that LTAS is a suitable approach to objectively describe changes in speech impairment severity due to STN-DBS therapy in patients with PD. We envisage these results as an important step toward a continuum development of technological solutions for the automated assessment of stimulation-induced dysarthria. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21644798.

Long-term success of low-frequency subthalamic nucleus stimulation for Parkinson's disease depends on tremor severity and symptom duration.

Patients with Parkinson's disease can develop axial symptoms, including speech, gait and balance difficulties. Chronic high-frequency (>100 Hz) deep brain stimulation can contribute to these impairments while low-frequency stimulation (<100 Hz) may improve symptoms but only in some individuals. Factors predicting which patients benefit from low-frequency stimulation in the long term remain unclear. This study aims to confirm that low-frequency stimulation improves axial symptoms, and to go further to also explore which factors predict the durability of its effects. We recruited patients who developed axial motor symptoms while using high-frequency stimulation and objectively assessed the short-term impact of low-frequency stimulation on axial symptoms, other aspects of motor function and quality of life. A retrospective chart review was then conducted on a larger cohort to identify which patient characteristics were associated with not only the need to trial low-frequency stimulation, but also those which predicted its sustained use. Among 20 prospective patients, low-frequency stimulation objectively improved mean motor and axial symptom severity and quality of life in the short term. Among a retrospective cohort of 168 patients, those with less severe tremor and those in whom axial symptoms had emerged sooner after subthalamic nucleus deep brain stimulation were more likely to be switched to and remain on long-term low-frequency stimulation. These data suggest that low-frequency stimulation results in objective mean improvements in overall motor function and axial symptoms among a group of patients, while individual patient characteristics can predict sustained long-term benefits. Longer follow-up in the context of a larger, controlled, double-blinded study would be required to provide definitive evidence of the role of low-frequency deep brain stimulation.

Guidelines for Speech Recording and Acoustic Analyses in Dysarthrias of Movement Disorders.

Most patients with movement disorders have speech impairments resulting from sensorimotor abnormalities that affect phonatory, articulatory, and prosodic speech subsystems. There is widespread cross-discipline use of speech recordings for diagnostic and research purposes, despite which there are no specific guidelines for a standardized method. This review aims to combine the specific clinical presentations of patients with movement disorders, existing acoustic assessment protocols, and technological advances in capturing speech to provide a basis for future research in this field and to improve the consistency of clinical assessments. We considered 3 areas: the recording environment (room, seating, background noise), the recording process (instrumentation, vocal tasks, elicitation of speech samples), and the acoustic outcome data. Four vocal tasks, namely, sustained vowel, sequential and alternating motion rates, reading passage, and monologues, are integral aspects of motor speech assessment. Fourteen acoustic vocal speech features, including their hypothesized pathomechanisms with regard to typical occurrences in hypokinetic or hyperkinetic dysarthria, are hereby recommended for quantitative exploratory analysis. Using these acoustic features and experimental speech data, we demonstrated that the hyperkinetic dysarthria group had more affected speech dimensions compared with the healthy controls than had the hypokinetic speakers. Several contrasting speech patterns between both dysarthrias were also found. This article is the first attempt to provide initial recommendations for a standardized way of recording the voice and speech of patients with hypokinetic or hyperkinetic dysarthria; thus allowing clinicians and researchers to reliably collect, acoustically analyze, and compare vocal data across different centers and patient cohorts. © 2020 International Parkinson and Movement Disorder Society.

Non-pharmacological Treatment Challenges in Early Parkinson's Disease for Axial and Cognitive Symptoms: A Mini Review.

Background: Parkinson's disease (PD) is now known to be a multisystemic heterogeneous neurodegenerative disease, including a wide spectrum of both motor and non-motor symptoms. PD patients' management must encompass a multidisciplinary approach to effectively address its complex nature. There are still challenges in terms of treating axial (gait, balance, posture, speech, and swallowing) and cognitive symptoms that typically arise with disease progression becoming poorly responsive to dopaminergic or surgical treatments. Objective: The objectives of the study are to further establish the presentation of axial and cognitive symptoms in early PD [Hoehn and Yahr (H&Y) scale ≤ 2] and to discuss the evidence for non-pharmacological approaches in early PD. Results: Mild and subtle changes in the investigated domains can be present even in early PD. Over the last 15 years, a few randomized clinical trials have been focused on these areas. Due to the low number of studies and the heterogeneity of the results, no definitive recommendations are possible. However, positive results have been obtained, with effective treatments being high-intensity treadmill and cueing for gait disturbances, high-intensity voice treatment, video-assisted swallowing therapy for dysphagia, and warm-up exercises and Wii FitTM training for cognition. Conclusions: Considering the association of motor, speech, and cognitive function, future trials should focus on multidisciplinary approaches to combined non-pharmacological management. We highlight the need for a more unified approach in managing these "orphan" symptoms, from the very beginning of the disease. The concept "the sooner the better" should be applied to multidisciplinary non-pharmacological management in PD.

Serotonin Expression in the Song Circuitry of Adult Male Zebra Finches.

Serotonin is an important neurotransmitter of the brain, but its role in song control remains to be fully demonstrated. Using male zebra finches (Taeniopygia guttata) that have song learning and production capabilities, we analysed the serotonin expression levels in the song nuclei and adjacent areas (peri-song nuclei) using immunohistochemistry. Key song nuclei were identified using combinations of Hoechst, choline acetyltransferase, and a neurofilament (NN18) marker in reference to the ZEBrA atlas. Mean serotonin expression was highest in interfacial nucleus (Nif) and lower in the other song nuclei in the following order (in order of highest first): interfacial nucleus (Nif) > Area X > dorsomedial part of the intercollicular nucelus (DM) > robust nucleus of the archistriatum (RA) > lateral magnocellular nucleus of the anterior neostriatum (LMAN) > ventral respiratory group (VRG) > dorsolateral nucleus of the medial thalamus (DLM) > the nucleus HVC (proper name) > tracheosyringeal motor nucleus (nXIIts). However, the mean serotonin expression (in order of highest first) in the peri-song nuclei regions was: peri-DM > peri-nXIIts > supra-peri-HVC > peri-RA > peri-DLM > peri-Area X > infra-peri-HVC > peri-VRG > peri-LMAN > peri-Nif. Interestingly, serotoninergic fibers immunostained for serotonin or the serotonin transporter can be found as a basket-like peri-neuronal structure surrounding cholinergic cell bodies, and appear to form contacts onto dopaminergic neurones. In summary, serotonin fibers are present at discrete song nuclei, and peri-song nuclei regions, which suggest serotonin may have a direct and/or modulatory role in song control.

Short Versus Conventional Pulse-Width Deep Brain Stimulation in Parkinson's Disease: A Randomized Crossover Comparison.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN-DBS patients has not been evaluated. OBJECTIVE: To compare the effect of short PW settings using 30-µs with conventional 60-µs settings on stimulation-induced dysarthria in Parkinson's disease patients with previously implanted STN-DBS systems. METHODS: In this single-center, double-blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN-DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30-µs or 60-µs settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures. RESULTS: There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30-µs settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation. CONCLUSIONS: Short PW settings using 30 µs did not alter dysarthric speech in chronic STN-DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings. © 2019 International Parkinson and Movement Disorder Society.

Effect of Low versus High Frequency Subthalamic Deep Brain Stimulation on Speech Intelligibility and Verbal Fluency in Parkinson's Disease: A Double-Blind Study.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) is an established treatment for late stage Parkinson's disease (PD). Speech intelligibility (SI) and verbal fluency (VF) have been shown to deteriorate following chronic STN-DBS. It has been suggested that speech might respond favourably to low frequency stimulation (LFS). OBJECTIVE: We examined how SI, perceptual speech characteristics, phonemic and semantic VF and processes underlying it (clustering and switching) respond to LFS of 60 and 80 Hz in comparison to high frequency stimulation (HFS) (110, 130 and 200 Hz). METHODS: In this double-blind study, 15 STN-DBS PD patients (mean age 65, SD = 5.8, 14 right handed, three females), were assessed at five stimulation frequencies: 60 Hz, 80 Hz, 110 Hz, 130 Hz and 200 Hz. In addition to the clinical neurological assessment of speech, VF and SI were assessed. RESULTS: SI and in particular articulation, respiration, phonation and prosody improved with LFS (all p < 0.05). Phonemic VF switching improved with LFS (p = 0.005) but this did not translate to an improved phonemic VF score. A trend for improved semantic VF was found. A negative correlation was found between perceptual characteristics of speech and duration of chronic stimulation (all p < 0.05). CONCLUSIONS: These findings highlight the need for meticulous programming of frequency to maximise SI in chronic STN-DBS. The findings further implicate stimulation frequency in changes to specific processes underlying VF, namely phonemic switching and demonstrate the potential to address such deficits through advanced adjustment of stimulation parameters.

The Effect of Short Pulse Width Settings on the Therapeutic Window in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60µs, but there is limited data available on the effect of shorter PWs. OBJECTIVE: To define the TW of STN-DBS in PD at PW of 30µs (PW30) relative to standard PW settings at 60µs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions. METHODS: Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30. RESULTS: The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30. CONCLUSIONS: STN-DBS in PD patients using a PW of 30µs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30µs settings.

Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. OBJECTIVES: To assess the relevance of pyramidal tract activation with STN-DBS in PD. METHODS: In a multimodal, blinded study in 20 STN-DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. RESULTS: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a "lateral-type" speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. CONCLUSIONS: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society.

A review of brain circuitries involved in stuttering.

Stuttering has been the subject of much research, nevertheless its etiology remains incompletely understood. This article presents a critical review of the literature on stuttering, with particular reference to the role of the basal ganglia (BG). Neuroimaging and lesion studies of developmental and acquired stuttering, as well as pharmacological and genetic studies are discussed. Evidence of structural and functional changes in the BG in those who stutter indicates that this motor speech disorder is due, at least in part, to abnormal BG cues for the initiation and termination of articulatory movements. Studies discussed provide evidence of a dysfunctional hyperdopaminergic state of the thalamocortical pathways underlying speech motor control in stuttering. Evidence that stuttering can improve, worsen or recur following deep brain stimulation for other indications is presented in order to emphasize the role of BG in stuttering. Further research is needed to fully elucidate the pathophysiology of this speech disorder, which is associated with significant social isolation.

Long-term outcome of subthalamic nucleus deep brain stimulation for Parkinson's disease using an MRI-guided and MRI-verified approach.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) represents a well-established treatment for patients with advanced Parkinson's disease (PD) insufficiently controlled with medical therapies. This study presents the long-term outcomes of patients with PD treated with STN-DBS using an MRI-guided/MRI-verified approach without microelectrode recording. METHODS: A cohort of 41 patients who underwent STN-DBS were followed for a minimum period of 5 years, with a subgroup of 12 patients being followed for 8-11 years. Motor status was evaluated using part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III), in on- and off-medication/on-stimulation conditions. Preoperative and postoperative assessments further included activities of daily living (UPDRS-II), motor complications (UPDRS-IV), neuropsychological and speech assessments, as well as evaluation of quality of life. Active contacts localisation was calculated and compared with clinical outcomes. RESULTS: STN-DBS significantly improved the off-medication UPDRS-III scores, compared with baseline. However, UPDRS scores increased over time after DBS. Dyskinesias, motor fluctuations and demands in dopaminergic medication remained significantly reduced in the long term. Conversely, UPDRS-III on-medication scores deteriorated at 5 and 8 years, mostly driven by axial and bradykinesia subscores. Quality of life, as well as depression and anxiety scores, did not significantly change at long-term follow-up compared with baseline. In our series, severe cognitive decline was observed in 17.1% and 16.7% of the patients at 5 and 8 years respectively. CONCLUSIONS: Our data confirm that STN-DBS, using an MRI-guided/MRI-verified technique, remains an effective treatment for motor 'off' symptoms of PD in the long term with low morbidity.

Predictive factors of speech intelligibility following subthalamic nucleus stimulation in consecutive patients with Parkinson's disease.

Speech changes after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can be variable, with the majority of patients experiencing speech deterioration over time. The aim of this study was to describe the perceptual characteristics of speech following chronic STN-DBS and to analyze clinical and surgical factors that could predict speech change. Fifty-four consecutive patients (34 men; mean age ± standard deviation (SD), 58.8 ± 6.3 years; mean ± SD disease duration, 12.5 ± 4.7 years; mean ± SD levodopa equivalent, 1556 ± 671 mg/day; mean ± SD Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) off-medication score, 48.1 ± 17.9 [range, 20-89]; and mean ± SD UPDRS-III on-medication score, 12.4 ± 7.8 [range, 2-31]) participated in this study. They were assessed before and at 1 year after surgery using the Assessment of Intelligibility for the Dysarthric Speech, the perceptual scale from Darley et al., and the UPDRS-III. Speech intelligibility deteriorated on average by 14.4% (P = 0.0006) after 1 year of STN-DBS when off-medication and by 12.3% (P = 0.001) when on-medication. The effect on speech was not linked to age at surgery, unlike the effect on motor outcome. The most significant predictive factors for deterioration of speech intelligibility when patients were off-medication/on-stimulation were lower preoperative speech intelligibility on-medication, longer disease duration, and medially placed left hemisphere active electrode contact. Speech change after STN-DBS is variable and multifactorial. Consistent preoperative speech evaluation would help inform patients about the possible effects of surgery. Appropriate consideration of speech deficits might assist surgical targeting, particularly of the left electrode.

Treatment of dysarthria following subthalamic nucleus deep brain stimulation for Parkinson's disease.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for patients with Parkinson's disease (PD). Speech impairment is a frequent side effect of the surgery. This study examined the efficacy of an intensive speech treatment, the Lee Silverman Voice Treatment (LSVT) on dysarthria after STN-DBS. METHODS: The LSVT was administered to 10 patients with STN-DBS (surgical group) and 10 patients without (medical group). Patients were assessed before, immediately after, and 6 months following the speech treatment using sustained phonation, a speech intelligibility scale, and monologue. Vocal loudness, speech intelligibility, and perceptual ratings were the primary outcome measures. RESULTS: Vocal loudness and perceptual scores improved significantly across tasks for the medical group only. Speech intelligibility did not significantly change for either group. Results in the surgical group were variable, with some patients deteriorating. CONCLUSIONS: Treatment of dysarthria following STN-DBS needs further investigation because of the variable response to LSVT.

Functional magnetic resonance imaging exploration of combined hand and speech movements in Parkinson's disease.

Among the repertoire of motor functions, although hand movement and speech production tasks have been investigated widely by functional neuroimaging, paradigms combining both movements have been studied less so. Such paradigms are of particular interest in Parkinson's disease, in which patients have specific difficulties performing two movements simultaneously. In 9 unmedicated patients with Parkinson's disease and 15 healthy control subjects, externally cued tasks (i.e., hand movement, speech production, and combined hand movement and speech production) were performed twice in a random order and functional magnetic resonance imaging detected cerebral activations, compared to the rest. F-statistics tested within-group (significant activations at P values < 0.05, familywise error corrected), between-group, and between-task comparisons (regional activations significant at P values < 0.001, uncorrected, with cluster size > 10 voxels). For control subjects, the combined task activations comprised the sum of those obtained during hand movement and speech production performed separately, reflecting the neural correlates of performing movements sharing similar programming modalities. In patients with Parkinson's disease, only activations underlying hand movement were observed during the combined task. We interpreted this phenomenon as patients' potential inability to recruit facilitatory activations while performing two movements simultaneously. This lost capacity could be related to a functional prioritization of one movement (i.e., hand movement), in comparison with the other (i.e., speech production). Our observation could also reflect the inability of patients with Parkinson's disease to intrinsically engage the motor coordination necessary to perform a combined task.

Effects of medication and subthalamic nucleus deep brain stimulation on tongue movements in speakers with Parkinson's disease using electropalatography: a pilot study.

Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using electropalatography (EPG). Two patients, PT1 and PT2, were studied under four conditions: on and off medication and ON and OFF stimulation. The EPG protocol consisted of a number of target words with alveolar and velar stops, repeated 10 times in random order. The motor part III of the Unified Parkinson Disease Rating Scale (UPDRS) indicated significantly improved motor scores in the ON stimulation condition in both patients. However, PT1's articulation patterns deteriorated with stimulation whereas PT2 showed improving articulatory accuracy in the same condition. The results revealed different effects of stimulation and medication on articulation particularly with regard to timing. The study quantified less articulatory undershoot for velar stops in comparison to alveolars. Furthermore, the findings provided preliminary evidence that stimulation with medication has a more detrimental effect on articulation than stimulation without medication.

Self-perception of speech changes in patients with Parkinson's disease following deep brain stimulation of the subthalamic nucleus.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves the motor difficulties experienced by patients with Parkinson's disease (PD); however, the effects on speech are variable. In this study, patients rated their current post-surgery speech difficulties using the Voice Handicap Index (VHI) and used the same measure to retrospectively rate their pre-surgery speech. Scores pre- and post-surgery were also available on the UPDRS-III, and the patients' intelligibility was assessed by an independent listener. A control group of non-surgical patients with PD (medical group) also completed the VHI for comparison. VHI scores deteriorated equally in the two groups. However, the variability of the change scores in the surgical group was significantly greater than in the medical group. The correlation between the changes in the VHI and UPDRS scores for the surgical group was not significant. Correlations between the VHI scores and intelligibility were significant both before and after surgery, suggesting that patients accurately perceive their difficulties. The findings confirm the variability in the speech difficulties of patients following STN-DBS. The patients' ability to use the VHI offers a means of assessing the effects of their speech on their quality-of-life, and may be clinically useful post-STN-DBS.