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Background: Remote objective tests may supplement in-clinic examination to better inform treatment decisions. Previous cross-sectional studies presented objective speech metrics as potential markers of Multiple Sclerosis (MS) disease progression., Objective: To examine the short-term stability and long-term sensitivity of speech metrics to MS progression., Methods: We prospectively recorded speech from people with MS at baseline, six, twelve weeks, and at ten months or longer after baseline (1y+). Only people with a definite diagnosis of MS and without other potential causes of dysarthria were included. Speech tasks comprehended 1) a sustained vowel /a/, 2) saying the days of the week, 3) repeating the non-word pa-ta-ka multiple times as fast as possible, 4) reading the Grandfather Passage, and 5) telling a personal story. We selected speech metrics of interest according to their association with MS presence, correlation with general disability, and short-term metric stability in the absence of disease progression. Selected speech metrics were analysed for short- versus long-term changes in the whole MS cohort and in the clinically stable versus progression subgroups at 1y+., Results: Sixty-nine people with MS participated (76.8 % female, age mean 47.5 ± 11.1 SD, EDSS median 3.5, interquartile range 3.5). Twenty-six unique speech metrics satisfied the suitability criteria. On average, reading rate improved 3.5 % for all people with MS and 6.5 % for slow readers with MS from baseline to the six-week, driven by a reduction in pauses. At 1y+, participants showed a 3.1 % average reduction in vocalization time during the reading task, which was similar in the progression (n = 29) and non-progression (n = 40) groups and thus unrelated to disease progression. Both findings are in the opposite direction of what would be generally expected for deterioration in speech performance and might be attributable to familiarity and training effects. Other speech metrics showed either negligible change or a similar variability between short-term and long-term differences., Conclusion: Most individual long-term changes were small and within short-term variability intervals, irrespective of clinical disease progression. Familiarity and practice effects might have blunted the measurement of change. The present lack of longitudinal sensitivity of speech in MS contradicts previous cross-sectional findings and requires further investigation., Competing Interests: Declaration of competing interest Adam Vogel is Chief Science Officer of Redenlab Inc. Anneke van der Walt served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche She has received speaker's honoraria and travel support from Novartis, Roche, and Merck. She receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. Frederique Boonstra has nothing to disclose. Gustavo Noffs works in scientific development for Redenlab Inc. Helmut Butzkueven has received institutional (Monash University) funding from Biogen, F. Hoffmann-La Roche Ltd, Merck, Alexion, CSL, and Novartis; has carried out contracted research for Novartis, Merck, F. Hoffmann-La Roche Ltd and Biogen; has taken part in speakers’ bureaus for Biogen, Genzyme, UCB, Novartis, F. Hoffmann-La Roche Ltd and Merck; has received personal compensation from Oxford Health Policy Forum for the Brain Health Steering Committee. Scott Kolbe receives grant income from the National Health and Medical Research Council of Australia and has received honoraria from Novartis, Biogen and Merck Thushara Perera has nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Functional magnetic resonance imaging (fMRI) can improve our understanding of neural processes subserving motor speech function. Yet its reproducibility remains unclear. This study aimed to evaluate the reproducibility of fMRI using a word repetition task across two time points., Methods: Imaging data from 14 healthy controls were analysed using a multi-level general linear model., Results: Significant activation was observed during the task in the right hemispheric cerebellar lobules IV-V, right putamen, and bilateral sensorimotor cortices. Activation between timepoints was found to be moderately reproducible across time in the cerebellum but not in other brain regions., Discussion: Preliminary findings highlight the involvement of the cerebellum and connected cerebral regions during a motor speech task. More work is needed to determine the degree of reproducibility of speech fMRI before this could be used as a reliable marker of changes in brain activity., Competing Interests: GN and AdV were employed by Redenlab Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kenyon, Boonstra, Noffs, Morgan, Vogel, Kolbe and Van Der Walt.)

Up to half of all people with multiple sclerosis experience communication difficulties due to dysarthria, a disorder that impacts the motor aspects of speech production. Dysarthria in multiple sclerosis is linked to cerebellar dysfunction, disease severity and lesion load, but the neuroanatomical substrates of these symptoms remain unclear. In this study, 52 participants with multiple sclerosis and 14 age- and sex-matched healthy controls underwent structural and diffusion MRI, clinical assessment of disease severity and cerebellar dysfunction and a battery of motor speech tasks. Assessments of regional brain volume and white matter integrity, and their relationships with clinical and speech measures, were undertaken. White matter tracts of interest included the interhemispheric sensorimotor tract, cerebello-thalamo-cortical tract and arcuate fasciculus, based on their roles in motor and speech behaviours. Volumetric analyses were targeted to Broca's area, Wernicke's area, the corpus callosum, thalamus and cerebellum. Our results indicated that multiple sclerosis participants scored worse on all motor speech tasks. Fixel-based diffusion MRI analyses showed significant evidence of white matter tract atrophy in each tract of interest. Correlational analyses further indicated that higher speech naturalness-a perceptual measure of dysarthria-and lower reading rate were associated with axonal damage in the interhemispheric sensorimotor tract and left arcuate fasciculus in people with multiple sclerosis. Axonal damage in all tracts of interest also correlated with clinical scales sensitive to cerebellar dysfunction. Participants with multiple sclerosis had lower volumes of the thalamus and corpus callosum compared with controls, although no brain volumetrics correlated with measures of dysarthria. These findings indicate that axonal damage, particularly when measured using diffusion metrics, underpin dysarthria in multiple sclerosis., Competing Interests: K.H.K., F.M.C.B., M.S. and A.M. have nothing to disclose. A.v.d.W. served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche; has received speaker’s honoraria and travel support from Novartis, Roche and Merck; and receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. A.P.V. is the chief science officer of Redenlab Inc. G.N. works in the scientific development for Redenlab Inc. S.K. received unrestricted research grants from Biogen and grant support from MS Research Australia. I.H.H receives grants from the National Health and Medical Research Council and honoraria from Steminent Biotherapeutics and PTC therapeutics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Smart devices are widely available and capable of quickly recording and uploading speech segments for health-related analysis. The switch from laboratory recordings with professional-grade microphone setups to remote, smart device-based recordings offers immense potential for the scalability of voice assessment. Yet, a growing body of literature points to a wide heterogeneity among acoustic metrics for their robustness to variation in recording devices. The addition of consumer-grade plug-and-play microphones has been proposed as a possible solution. The aim of our study was to assess if the addition of consumer-grade plug-and-play microphones increases the acoustic measurement agreement between ultra-portable devices and a reference microphone., Methods: Speech was simultaneously recorded by a reference high-quality microphone commonly used in research and by two configurations with plug-and-play microphones. Twelve speech-acoustic features were calculated using recordings from each microphone to determine the agreement intervals in measurements between microphones. Agreement intervals were then compared to expected deviations in speech in various neurological conditions. Each microphone's response to speech and to silence was characterized through acoustic analysis to explore possible reasons for differences in acoustic measurements between microphones. The statistical differentiation of two groups, neurotypical and people with multiple sclerosis, using metrics from each tested microphone was compared to that of the reference microphone., Results: The two consumer-grade plug-and-play microphones favored high frequencies (mean center of gravity difference ≥ +175.3 Hz) and recorded more noise (mean difference in signal to noise ≤ -4.2 dB) when compared to the reference microphone. Between consumer-grade microphones, differences in relative noise were closely related to distance between the microphone and the speaker's mouth. Agreement intervals between the reference and consumer-grade microphones remained under disease-expected deviations only for fundamental frequency (f0, agreement interval ≤0.06 Hz), f0 instability (f0 CoV, agreement interval ≤0.05%), and tracking of second formant movement (agreement interval ≤1.4 Hz/ms). Agreement between microphones was poor for other metrics, particularly for fine timing metrics (mean pause length and pause length variability for various tasks). The statistical difference between the two groups of speakers was smaller with the plug-and-play than with the reference microphone., Conclusion: Measurement of f0 and F2 slope was robust to variation in recording equipment, while other acoustic metrics were not. Thus, the tested plug-and-play microphones should not be used interchangeably with professional-grade microphones for speech analysis. Plug-and-play microphones may assist in equipment standardization within speech studies, including remote or self-recording, possibly with small loss in accuracy and statistical power as observed in the current study., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Multiple sclerosis (MS) is a progressive disease that often affects the cerebellum. It is characterised by demyelination, inflammation, and neurodegeneration within the central nervous system. Damage to the cerebellum in MS is associated with increased disability and decreased quality of life. Symptoms include gait and balance problems, motor speech disorder, upper limb dysfunction, and oculomotor difficulties. Monitoring symptoms is crucial for effective management of MS. A combination of clinical, neuroimaging, and task-based measures is generally used to diagnose and monitor MS. This paper reviews the present and new tools used by clinicians and researchers to assess cerebellar impairment in people with MS (pwMS). It also describes recent advances in digital and home-based monitoring for people with MS., (© 2022. The Author(s).)

Neurodegenerative disease often affects speech. Speech acoustics can be used as objective clinical markers of pathology. Previous investigations of pathological speech have primarily compared controls with one specific condition and excluded comorbidities. We broaden the utility of speech markers by examining how multiple acoustic features can delineate diseases. We used supervised machine learning with gradient boosting (CatBoost) to delineate healthy speech from speech of people with multiple sclerosis or Friedreich ataxia. Participants performed a diadochokinetic task where they repeated alternating syllables. We subjected 74 spectral and temporal prosodic features from the speech recordings to machine learning. Results showed that Friedreich ataxia, multiple sclerosis and healthy controls were all identified with high accuracy (over 82%). Twenty-one acoustic features were strong markers of neurodegenerative diseases, falling under the categories of spectral qualia, spectral power, and speech rate. We demonstrated that speech markers can delineate neurodegenerative diseases and distinguish healthy speech from pathological speech with high accuracy. Findings emphasize the importance of examining speech outcomes when assessing indicators of neurodegenerative disease. We propose large-scale initiatives to broaden the scope for differentiating other neurological diseases and affective disorders.

Background: Upper limb tremor is common in people with multiple sclerosis (pwMS) and can affect day to day function, impacting on their tremor related quality of life (tremor-QOL). The Quality of Life in Essential Tremor Questionnaire (QUEST) is a tremor-QOL scale, however it has not been validated for use in pwMS. This is in contrast to the Multiple Sclerosis Impact Scale (MSIS-29), a MS health related QOL (MS-QOL) scale validated in pwMS. The aim of this study was to quantify tremor-QOL in pwMS using both the QUEST and MSIS-29 and establish the convergent validity of the QUEST scale with the MSIS-29., Methods: Data were derived from an existing registered clinical trial studying the efficacy of Botox (onabotulinumtoxinA) compared to placebo in pwMS-related upper limb tremor (ACTRN12617000379314). We determined MS-related disability (Expanded Disability status scale score (EDSS)), tremor severity (Bain and Findley Clinical Tremor Rating Scale (Bain)), cerebellar function (Scale for the Assessment and rating of Ataxia (SARA)), and upper limb manual dexterity (9 Hole Peg Test (9-HPT)). The QUEST and MSIS-29 were used to quantify tremor-QOL and MS-QOL respectively. Convergent validity was investigated by examining the correlation between QUEST and MSIS-29, and the pattern of correlation of the two scales compared to the EDSS, SARA, BAIN and 9-HPT., Results: Our cohort of 57 patients (16 male; 41 female), mean age of 47.6, had moderate MS-related disability with median EDSS score of 5 (IQR = 3.5). Median Bain score was 8, indicating mild tremor severity, which corresponded to mild to moderately poor tremor-QOL given mean Quest Summary Index (QSI) of 45.7. QSI correlated to tremor severity as measured by Bain total score (rs(55) = 0.339, p < 0.01), manual dexterity as measured by 9-HPT (rs(55) = 0.304, p < 0.05), and MS disease activity measured by EDSS (rs(55) = 0.347, p < 0.01). MSIS-29 also showed correlations to EDSS, and 9-HPT, but did not correlate to Bain total score. There was a strong relationship between QSI and MSIS-29 in pwMS (r(55) = 0.709, p < 0.01)., Conclusion: In this cross-sectional study, we found that both the MS-QOL and tremor-QOL of pwMS with upper limb tremor was reduced. We were also the first to demonstrate that tremor-QOL in pwMS with upper limb tremor can be measured using the QUEST, which may be better suited for use in pwMS affected by arm-tremor than the MSIS-29. There is a lack of literature to specifically address tremor-QOL in pwMS, and more research is warranted., (Copyright © 2022. Published by Elsevier B.V.)

Background: Multiple Sclerosis (MS) pathology is likely to disrupt central auditory pathways, thereby affecting an individual's ability to discriminate speech from noise. Despite the importance of speech discrimination in daily communication, it's characterization in the context of MS remains limited. This cross-sectional study evaluated speech discrimination in MS under "real world" conditions where sentences were presented in ecologically valid multi-talker speech or broadband noise at several signal-to-noise ratios (SNRs)., Methods: Pre-recorded Bamford-Kowal-Bench sentences were presented at five signal-to-noise ratios (SNR) in one of two background noises: speech-weighted noise and eight-talker babble. All auditory stimuli were presented via headphones to control (n = 38) and MS listeners with mild (n = 20), moderate (n = 16) and advanced (n = 10) disability. Disability was quantified by the Kurtzke Expanded Disability Status Scale (EDSS) and scored by a neurologist. All participants passed a routine audiometric examination., Results: Despite normal hearing, MS psychometric discrimination curves which model the relationship between signal-to-noise ratio (SNR) and sentence discrimination accuracy in speech-weighted noise and babble did not change in slope (sentences/dB) but shifted to higher SNRs (dB) compared to controls. The magnitude of the shift in the curve systematically increased with greater disability. Furthermore, mixed-effects models identified EDSS score as the most significant predictor of speech discrimination in noise (odds ratio = 0.81; p < 0.001). Neither age, sex, disease phenotype or disease duration were significantly associated with speech discrimination performance in noise. Only MS listeners with advanced disability self-reported audio-attentional difficulty in a questionnaire designed to reflect auditory processing behaviours in daily life., Conclusion: Speech discrimination performance worsened systematically with greater disability, independent of age, sex, education, disease duration or disease phenotype. These results identify novel auditory processing deficits in MS and highlight that speech discrimination tasks may provide a viable non-invasive and sensitive means for disease monitoring in MS., (Copyright © 2020. Published by Elsevier B.V.)

Background and Purpose: Objective measurement of speech has shown promising results to monitor disease state in multiple sclerosis. In this study, we characterize the relationship between disease severity and speech metrics through perceptual (listener based) and objective acoustic analysis. We further look at deviations of acoustic metrics in people with no perceivable dysarthria., Methods: Correlations and regression were calculated between speech measurements and disability scores, brain volume, lesion load and quality of life. Speech measurements were further compared between three subgroups of increasing overall neurological disability: mild (as rated by the Expanded Disability Status Scale ≤2.5), moderate (≥3 and ≤5.5) and severe (≥6)., Results: Clinical speech impairment occurred majorly in people with severe disability. An experimental acoustic composite score differentiated mild from moderate (P < 0.001) and moderate from severe subgroups (P = 0.003), and correlated with overall neurological disability (r = 0.6, P < 0.001), quality of life (r = 0.5, P < 0.001), white matter volume (r = 0.3, P = 0.007) and lesion load (r = 0.3, P = 0.008). Acoustic metrics also correlated with disability scores in people with no perceivable dysarthria., Conclusions: Acoustic analysis offers a valuable insight into the development of speech impairment in multiple sclerosis. These results highlight the potential of automated analysis of speech to assist in monitoring disease progression and treatment response., (© 2020 European Academy of Neurology.)

The most complex interactions between human beings occur through speech, and often in the presence of background noise. Understanding speech in noisy environments requires the integrity of highly integrated and widespread auditory networks likely to be impacted by multiple sclerosis (MS) related neurogenic injury. Despite the impact auditory communication has on a person's ability to navigate the world, build relationships, and maintain employability; studies of speech-in-noise (SiN) perception in people with MS (pwMS) have been minimal to date. Thus, this paper presents a dataset related to the acquisition of pure-tone thresholds, SiN performance and questionnaire responses in age-matched controls and pwMS. Bilateral pure-tone hearing thresholds were obtained at frequencies of 250 hertz (Hz), 500 Hz, 750 Hz, 1000 Hz, 1500 Hz, 2000 Hz, 4000 Hz, 6000 Hz and 8000 Hz, and hearing thresholds were defined as the lowest level at which the tone was perceived 50% of the time. Thresholds at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz were used to calculate the four-tone average for each participant, and only those with a bilateral four tone average of ≤ 25 dB HL were included in the analysis. To investigate SiN performance in pwMS, pre-recorded Bamford-Kowal-Bench (BKB) sentences were presented binaurally through headphones at five signal-to-noise ratios (SNR) in two noise conditions: speech-weighted noise and multi-talker babble. Participants were required to verbally repeat each sentence they had just heard; or indicate their inability to do so. A 33-item questionnaire, based on validated inventories for specific adult clinical populations with abnormal auditory processing, was used to evaluate auditory processing in daily life for pwMS. For analysis, pwMS were grouped according to their Expanded Disability Status Scale (EDSS) score as rated by a neurologist. PwMS with EDSS scores ≤ 1.5 were classified as 'mild' ( n  = 20); between 2 and 4.5 as 'moderate' ( n  = 16) and between 5 and 7 as 'advanced' ( n  = 10) and were compared to neurologically healthy controls ( n  = 38). The outcomes of the SiN task conducted in pwMS can be found in Iva et al., (2021). The present data has important implications for the timing and delivery of preparatory education to patients, family, and caregivers about communication abilities in pwMS. This dataset will also be valuable for the reuse/reanalysis required for future investigations into the clinical utility of SiN tasks to monitor disease progression., Competing Interests: This research was supported by internal lab funds at Monash University, Clayton, VIC, Australia. Dr Anneke van der Walt has received travel support and served on advisory boards for Novartis, Biogen, Merck Serono and Roche. She receives research support from the National Health and Medical Research Council of Australia and MS Research Australia. Dr Joanne Fielding has received funding for MS research from Genzyme, Biogen, and Novartis., (© 2020 The Authors.)

Wearing face masks (alongside physical distancing) provides some protection against infection from COVID-19. Face masks can also change how people communicate and subsequently affect speech signal quality. This study investigated how three common face mask types (N95, surgical, and cloth) affected acoustic analysis of speech and perceived intelligibility in healthy subjects. Acoustic measures of timing, frequency, perturbation, and power spectral density were measured. Speech intelligibility and word and sentence accuracy were also examined using the Assessment of Intelligibility of Dysarthric Speech. Mask type impacted the power distribution in frequencies above 3 kHz for the N95 mask, and above 5 kHz in surgical and cloth masks. Measures of timing and spectral tilt mainly differed with N95 mask use. Cepstral and harmonics to noise ratios remained unchanged across mask type. No differences were observed across conditions for word or sentence intelligibility measures; however, accuracy of word and sentence translations were affected by all masks. Data presented in this study show that face masks change the speech signal, but some specific acoustic features remain largely unaffected (e.g., measures of voice quality) irrespective of mask type. Outcomes have bearing on how future speech studies are run when personal protective equipment is worn.

Speech production relies on motor control and cognitive processing and is linked to cerebellar function. In diseases where the cerebellum is impaired, such as multiple sclerosis (MS), speech abnormalities are common and can be detected by instrumental assessments. However, the potential of speech assessments to be used to monitor cerebellar impairment in MS remains unexplored. The aim of this study is to build an objectively measured speech score that reflects cerebellar function, pathology and quality of life in MS. Eighty-five people with MS and 21 controls participated in the study. Speech was independently assessed through objective acoustic analysis and blind expert listener ratings. Cerebellar function and overall disease disability were measured through validated clinical scores; cerebellar pathology was assessed via magnetic resonance imaging, and validated questionnaires informed quality of life. Selected speech variables were entered in a regression model to predict cerebellar function. The resulting model was condensed into one composite speech score and tested for prediction of abnormal 9-hole peg test (9HPT), and for correlations with the remaining cerebellar scores, imaging measurements and self-assessed quality of life. Slow rate of syllable repetition and increased free speech pause percentage were the strongest predictors of cerebellar impairment, complemented by phonatory instability. Those variables formed the acoustic composite score that accounted for 54% of variation in cerebellar function, correlated with cerebellar white matter volume (r = 0.3, p = 0.017), quality of life (r = 0.5, p < 0.001) and predicted an abnormal 9HPT with 85% accuracy. An objective multi-feature speech metric was highly representative of motor cerebellar impairment in MS.

Background: Tremor is present in almost half of multiple sclerosis (MS) patients. The lack of understanding of its pathophysiology is hampering progress in development of treatments., Objectives: To clarify the structural and functional brain changes associated with the clinical phenotype of upper limb tremor in people with MS., Methods: Fifteen healthy controls (46.1 ± 15.4 years), 27 MS participants without tremor (46.7 ± 11.6 years) and 42 with tremor (46.6 ± 11.5 years) were included. Tremor was quantified using the Bain score (0-10) for overall severity, handwriting and Archimedes spiral drawing. Functional magnetic resonance imaging activations were compared between participants groups during performance of a joystick task designed to isolate tremulous movement. Inflammation and atrophy of cerebello-thalamo-cortical brain structures were quantified., Results: Tremor participants were found to have atrophy of the cerebellum and thalamus, and higher ipsilateral cerebellar lesion load compared to participants without tremor ( p  < 0.020). We found higher ipsilateral activation in the inferior parietal lobule, the premotor cortex and supplementary motor area in MS tremor participants compared to MS participants without tremor during the joystick task. Finally, stronger activation in those areas was associated with lower tremor severity., Conclusion: Subcortical neurodegeneration and inflammation along the cerebello-thalamo-cortical and cortical functional neuroplasticity contribute to the severity of tremor in MS.

Background: Treatment of tremor in MS is an unmet need. OnabotulinumtoxinA (BoNT-A) has shown promising results; however, little is known regarding its effects on the brain. The clinical presentation of tremor MS is shown to depend on subcortical neural damage and cortical neural plasticity. This study aimed to identify effects of onabotulinumtoxinA (BoNT-A) on brain activation in MS and upper-limb tremor using functional MRI., Methods: Forty-three MS participants with tremor were randomized to receive intramuscular injections of placebo (n = 22) or BoNT-A (n = 21). Tremor was quantified using the Bain score (0-10) for severity, handwriting and Archimedes drawing at baseline, 6 weeks and 12 weeks. Functional MRI activation within two previously identified clusters, ipsilateral inferior parietal cortex (IPL) and premotor/supplementary motor cortex (SMC) of compensatory activity, was measured at baseline and 6 weeks., Results: Treatment with BoNT-A resulted in improved handwriting tremor at 6 weeks (p = 0.049) and 12 weeks (p = 0.014), and tremor severity -0.79 (p = 0.007) at 12 weeks. Furthermore, the patients that received BoNT-A showed a reduction in activation within the IPL (p = 0.034), but not in the SMC. The change in IPL activation correlated with the reduction in tremor severity from baseline to 12 weeks (β = 0.608; p = 0.015) in the BoNT-A group. No tremor and fMRI changes were seen in the placebo treated group., Conclusion: We have shown that reduction in MS-tremor severity after intramuscular injection with BoNT-A is associated with changes in brain activity in sensorimotor integration regions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Parkinson's disease (PD) frequently causes progressive deterioration in speech, voice and cognitive aspects of communication. These affect wellbeing and quality of life and are associated with caregiver strain and burden. Therapeutic singing groups can ameliorate PD-related communication disorders and increase social interaction and wellbeing for caregivers and care recipients., Objective: To analyse the effects of ParkinSong group singing sessions on Parkinson's communication and wellbeing outcomes for people with PD and caregivers over 12 months., Methods: A 4-armed controlled clinical trial compared ParkinSong with active non-singing control conditions over 12 months. Two dosage levels (weekly versus monthly) were available for each condition. ParkinSong comprised high-effort vocal, respiratory and speech exercises, group singing, and social interaction. PD-specific outcomes included vocal loudness, speech intelligibility, maximum phonation time, respiratory muscle strength, and voice related quality of life (QoL). Wellbeing outcomes were also measured for caregivers and care recipients., Results: We recruited 75 people with PD and 44 caregivers who attended weekly ParkinSong, monthly ParkinSong, weekly control or monthly control groups. We found significant improvements in the primary outcome of vocal loudness (p = 0.032), with weekly singers 5.13 dB louder (p = 0.044) and monthly singers 5.69 dB louder (p = 0.015) than monthly controls at 12 months. ParkinSong participants also showed greater improvements in voice-related QoL and anxiety. Caregivers who attended ParkinSong showed greater reductions in depression and stress scores., Conclusions: This 12-month controlled clinical trial of ParkinSong demonstrated improvements in speech loudness and voice-related QoL for participants with PD, and enhanced wellbeing for both caregivers and care recipients. No adverse effects were reported over 12 months and improvements were sustained.

Background: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy., New Method: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers., Results: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p =  0.002) in healthy subjects., Comparison With Existing Methods: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended., Conclusions: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Importance: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression., Observations: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis., Conclusion and Relevance: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Tremor of the upper limbs is a disabling symptom that is present during several neurological disorders and is currently without treatment. Functional MRI (fMRI) is an essential tool to investigate the pathophysiology of tremor and aid the development of treatment options. However, no adequately or standardized protocols for fMRI exists at present. Here we present a novel, online available fMRI task that could be used to assess the in vivo pathology of tremor. Objective: This study aims to validate the tremor-evoking potential of the fMRI task in a small group of tremor patients outside the scanner and assess the reproducibility of the fMRI task related activation in healthy controls. Methods: Twelve HCs were scanned at two time points (baseline and after 6-weeks). There were two runs of multi-band fMRI and the tasks included a "brick-breaker" joystick game. The game consisted of three conditions designed to control for most of the activation related to performing the task by contrasting the conditions: WATCH (look at the game without moving joystick), MOVE (rhythmic left/right movement of joystick without game), and PLAY (playing the game). Task fMRI was analyzed using FSL FEAT to determine clusters of activation during the different conditions. Maximum activation within the clusters was used to assess the ability to control for task related activation and reproducibility. Four tremor patients have been included to test ecological and construct validity of the joystick task by assessing tremor frequencies captured by the joystick. Results: In HCs the game activated areas corresponding to motor, attention and visual areas. Most areas of activation by our game showed moderate to good reproducibility (intraclass correlation coefficient (ICC) 0.531-0.906) with only inferior parietal lobe activation showing poor reproducibility (ICC 0.446). Furthermore, the joystick captured significantly more tremulous movement in tremor patients compared to HCs (p = 0.01) during PLAY, but not during MOVE. Conclusion: Validation of our novel task confirmed tremor-evoking potential and reproducibility analyses yielded acceptable results to continue further investigations into the pathophysiology of tremor. The use of this technique in studies with tremor patient will no doubt provide significant insights into the treatment options.

Background: Vocal impairment is one of the main debilitating symptoms of Parkinson disease (PD). The effect of levodopa on vocal function remains unclear., Objective: This study aimed to determine the effect of levodopa on electromyographic patterns of the laryngeal muscle in patients with PD., Study Design: This is a prospective interventional trial., Methods: Nineteen patients with PD-diagnosed by laryngeal electromyography-were enrolled. Cricothyroid and thyroarytenoid (TA) muscle activities were measured at rest and during muscle contraction (phonation), when participants were on and off medication (12 hours after the last levodopa dose)., Results: Prevalence of resting hypertonia in the cricothyroid muscle was similar in the off and on states (7 of 19, P = 1.00). Eight patients off medication and four patients on medication had hypertonic TA muscle at rest (P = 0.289). No electromyographic alterations were observed during phonation for either medication states., Conclusion: Despite a tendency for increased rest tracings in the TA muscle when participants were on medication, no association was found between laryngeal electromyography findings and levodopa + carbidopa administration., (Copyright © 2017. Published by Elsevier Inc.)