One side effect: two networks? Lateral and posteromedial stimulation spreads induce dysarthria in subthalamic deep brain stimulation for Parkinson's disease.

BACKGROUND: Stimulation-induced dysarthria (SID) is a troublesome and potentially therapy-limiting side effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson's disease (PD). To date, the origin of SID, and especially whether there is an involvement of cerebellar pathways as well as the pyramidal tract, remains a matter of debate. Therefore, this study aims to shed light on structural networks associated with SID and to derive a data-driven model to predict SID in patients with PD and STN-DBS. METHODS: Randomised, double-blinded monopolar reviews determining SID thresholds were conducted in 25 patients with PD and STN-DBS. A fibre-based mapping approach, implementing the calculation of fibr-wise ORs for SID, was employed to identify the distributional pattern of SID in the STN's vicinity. The ability of the data-driven model to classify stimulation volumes as 'causing SID' or 'not causing SID' was validated by calculating receiver operating characteristics (ROC) in an independent out-of-sample cohort comprising 14 patients with PD and STN-DBS. RESULTS: Local fibre-based stimulation maps showed an involvement of fibres running lateral and posteromedial to the STN in the pathogenesis of SID, independent of the investigated hemisphere. ROC analysis in the independent out-of-sample cohort resulted in a good fit of the data-driven model for both hemispheres (area under the curve (AUC)left=0.88, AUCright=0.88). CONCLUSIONS: This study reveals an involvement of both, cerebello-thalamic fibres, as well as the pyramidal tract, in the pathogenesis of SID in STN-DBS. The results may impact future postoperative programming strategies to avoid SID in patients with PD and STN-DBS TRIAL REGISTRATION NUMBER: DRKS00023221; German Clinical Trials Register (DRKS) Number.

Network Fingerprint of Stimulation-Induced Speech Impairment in Essential Tremor.

OBJECTIVE: This study was undertaken to gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). METHODS: Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was then validated in a leave-one-out design. RESULTS: Fibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al-Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p < 0.001) of the variance of stimulation-induced change in intelligibility in a leave-one-out analysis. INTERPRETATION: This study demonstrates that SID in essential tremor patients is associated with both motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in essential tremor patients with thalamic DBS. ANN NEUROL 2021;89:315-326.

Prosody matters: Preserved prominence marking strategies in people with Parkinson's disease independent of motor status.

While many studies focus on segmental variation in Parkinsonian speech, little is known about prosodic modulations reflecting the ability to adapt to communicative demands in people with Parkinson's disease (PwPD). This type of prosodic modulation is important for social interaction, and it involves modifications in speech melody (intonational level) and articulation of consonants and vowels (segmental level). The present study investigates phonetic cues of prosodic modulations with respect to different focus structures in mild dysarthric PwPD as a function of levodopa. Acoustic and kinematic speech parameters of 25 PwPD were assessed in two motor conditions. Speech production data from PwPD were collected before (medication-OFF) and after levodopa intake (medication-ON) by means of 3-D electromagnetic articulography. On the acoustic level, intensity, pitch, and syllable durations were analyzed. On the kinematic level, movement duration and amplitude were investigated. Spatio-temporal modulations of speech parameters were examined and compared across three different prosodic focus structures (out-of-focus, broad focus, contrastive focus) to display varying speech demands. Overall, levodopa had beneficial effects on motor performance, speech loudness, and pitch modulation. Acoustic syllable durations and kinematic movement durations did not change, revealing no systematic effects of motor status on the temporal domain. In contrast, there were spatial modulations of the oral articulators: tongue tip movements were smaller and lower lip movements were larger in amplitude under levodopa, reflecting a more agile and efficient articulatory movement under levodopa. Thus, respiratory-phonatory functions and consonant production improved, while syllable duration and tongue body kinematics did not change. Interestingly, prominence marking strategies were comparable between the medication conditions under investigation, and in fact, appear to be preserved in mild dysarthric PwPD.

An automatic measure for speech intelligibility in dysarthrias-validation across multiple languages and neurological disorders.

Introduction: Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework. Methods: The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants' speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed. Results: Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability. Discussion: The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.

Compensatory articulatory mechanisms preserve intelligibility in prodromal Parkinson's disease.

INTRODUCTION: Dysarthria is highly prevalent in patients with Parkinson's disease (PD) and speech changes have already been detected in patients with prodromal PD on the acoustic level. However, the present study directly tracks underlying articulatory movements with electromagnetic articulography to investigate early speech alterations on the kinematic level in isolated REM sleep behavior disorder (iRBD) and compares them to PD and control speakers. METHODS: Kinematic data of 23 control speakers, 22 speakers with iRBD, and 23 speakers with PD were collected. Amplitude, duration, and average speed of lower lip, tongue tip, and tongue body movements were analyzed. Naive listeners rated the intelligibility of all speakers. RESULTS: Patients with iRBD produced tongue tip and tongue body movements that were larger in amplitude and longer in duration compared to control speakers, while remaining intelligible. Compared to patients with iRBD, patients with PD had smaller, longer and slower tongue tip and lower lip movements, accompanied by lower intelligibility. Thus, the data indicate that the lingual system is already affected in prodromal PD. Furthermore, lower lip and especially tongue tip movements slow down and speech intelligibility decreases if motor impairment is more pronounced. CONCLUSION: Patients with iRBD adjust articulatory patterns to counteract incipient motor detriment on speech to maintain their intelligibility level.

Task-based profiles of language impairment and their relationship to cognitive dysfunction in Parkinson's disease.

OBJECTIVE: Parkinson's Disease (PD) is associated with both motor and non-motor problems, such as cognitive impairment. Particular focus in this area has been on the relationship between language impairment and decline in other cognitive functions, with the literature currently inconclusive on how the nature and degree of language impairment relate to cognition or other measures of disease severity. In addition, little information is available on how language problems identified in experimental task set-ups relate to competency in self-generated language paradigms such as picture description, monologues or conversations. This study aimed to inform clinical management of language impairment in PD by exploring (1) language performance across a range of experimental as well as self-generated language tasks, (2) how the relationship between these two aspects might be affected by the nature of the cognitive and language assessment; and (3) to what degree performance can be predicted across the language tasks. METHODS: 22 non-demented people with PD (PwPD) and 22 healthy control participants performed a range of cognitive and language tasks. Cognitive tasks included a screening assessment in addition to tests for set shifting, short term memory, attention, as well as letter and category fluency. Language was investigated in highly controlled grammar tasks as well as a Sentence Generation and a Narrative. RESULTS: The study highlighted impaired ability in set-shifting and letter fluency in the executive function tasks, and a higher rate of grammatical and lexical errors across all language tasks in the PD group. The performance in the grammar task was linked to set shifting ability, but error rates in Sentence Generation and Narrative were independent of this. There was no relevant relationship between performances across the three language tasks. CONCLUSIONS: Our results suggest that there is a link between executive function and language performance, but that this is task dependent in non-demented PwPD. This has implications for the management of language impairment in PD, both for assessment and for designing effective interventions.

Levodopa-Based Changes on Vocalic Speech Movements during Prosodic Prominence Marking.

The present study investigates speech changes in Parkinson's disease on the acoustic and articulatory level with respect to prosodic prominence marking. To display movements of the underlying articulators, speech data from 16 patients with Parkinson's disease were recorded using electromagnetic articulography. Speech tasks focused on strategies of prominence marking. Patients' ability to encode prominence in the laryngeal and supra-laryngeal domain is tested in two conditions to examine the influence of motor performance on speech production further: without dopaminergic medication and with dopaminergic medication. The data reveal that patients with Parkinson's disease are able to highlight important information in both conditions. They maintain prominence relations across- and within-accentuation by adjusting prosodic markers, such as vowel duration and pitch modulation, while the acoustic vowel space remains the same. For differentiating across-accentuation, not only intensity but also all temporal and spatial parameters related to the articulatory tongue body movements during the production of vowels are modulated to signal prominence. In response to the levodopa intake, gross motor performance improved significantly by 42%. The improvement in gross motor performance was accompanied by an improvement in speech motor performance in terms of louder speech and shorter, larger and faster tongue body movements. The tongue body is more agile under levodopa increase, a fact that is not necessarily detectable on the acoustic level but important for speech therapy.

Prominence marking in parkinsonian speech and its correlation with motor performance and cognitive abilities.

OBJECTIVES: Research suggests that people with Parkinson's disease (PwPD) do not only suffer from motor but also non-motor impairment. This interdisciplinary study investigated how prominence marking is influenced by problems on the motoric and cognitive level. MATERIALS AND METHODS: We collected speech production data from 38 native German speakers: 19 PwPD (under medication) with a mild to moderate motor impairment, 13 males and 6 females (mean 66.2 years old, SD = 7.7), and 19 healthy age- and gender-matched control participants (mean 65.4 years old, SD = 9.3). Target words were produced in an accented and unaccented condition within a speech production task. The data were analyzed for intensity, syllable duration, F0 and vowel production. Furthermore, we assessed motor impairment and cognitive functions, i.e. working memory, task-switching, attention control and speed of information processing. RESULTS: Both groups were able to mark prominence by increasing pitch, syllable duration and intensity and by adjusting their vowel production. Comparisons between PwPD and control participants revealed that the vowel space was smaller in PwPD even in mildly impaired speakers. Further, task-switching as an executive function, which was tested with the trail making test, was correlated with modulation of F0 and intensity in PwPD: the worse the task-switching performance, the stronger intensity and F0 were modulated (target overshoot). Moreover, motor impairment within the PwPD group was related to a decrease in the acoustic vowel space (target undershoot), which further resulted in a decrease in speech intelligibility and naturalness. This behaviour of target over- and undershoot indicates an inefficient way of prominence marking in PwPD with mildly affected speech. CONCLUSION: PwPD with signs of mild dysarthria did not differ from the control speakers with respect to their strategies of prominence marking. However, only the PwPD overused F0 and intensity in prominent positions. Overmodulation of F0 and intensity was correlated with the patient's task-switching ability and reflected abnormalities in the regulatory mechanism for expressing prosodic prominence. This is the first study to report a link between cognitive skills and speech production at the phonetic level in PwPD.

The effects of thalamic and posterior subthalamic deep brain stimulation on speech in patients with essential tremor - A prospective, randomized, doubleblind crossover study.

OBJECTIVE: To prospectively evaluate the effect of PSA- and VIM DBS on speech in ET patients. METHODS: Leads were implanted bilaterally with contacts placed in both VIM and PSA. Thirteen patients were analyzed pre- and postoperatively. Preoperative speech of ET patients was compared to healthy controls. PSA- and VIM-DBS were evaluated in a randomized, double-blind crossover phase. RESULTS: At preoperative baseline, we found reduced intelligibility. Differences in acoustic and VAS data ('ability to speak') compared to controls were gradient. Articulation rate could be predicted by disease duration. Decreased articulation rate, spirantization and voicing were found for PSA- and VIM-DBS. Targets did not differ in terms of speech deterioration. CONCLUSION: Speech in ET patients without DBS can be impaired, dependent on patient's individual characteristics. Both PSA- and VIM-DBS affect speech in a comparable way. Thus, the PSA can be considered an alternative DBS target in ET without higher risk of dysarthria.

Thalamic Deep Brain Stimulation in Essential Tremor Plus Is as Effective as in Essential Tremor.

The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn-Tolosa-Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.

Evaluation of a German version of the Bain and Findley Tremor ADL scale.

The Movement Disorder Society recommends the Bain and Findley Tremor ADL Scale to assess ADL in patients with ET. In 45 medically and 14 surgically (DBS) treated ET patients, a German version of the scale correlated well with tremor severity and quality of life and was sensitive to postoperative change.