Development of a primary cell model derived from porcine dorsal soft palate for foot-and-mouth disease virus research and diagnosis

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals that has a significant socio-economic impact. One concern associated with this disease is the ability of its etiological agent, the FMD virus (FMDV), to persist in its hosts through underlying mechanisms that remain to be elucidated. While persistence has been described in cattle and small ruminants, it is unlikely to occur in pigs. One of the factors limiting the progress in understanding FMDV persistence and, in particular, differential persistence is the lack of suitable in vitro models. A primary bovine cell model derived from the dorsal soft palate, which is the primary site of replication and persistence of FMDV in cattle, has been developed, and it seemed relevant to develop a similar porcine model. Cells from two sites of FMDV replication in pigs, namely, the dorsal soft palate and the oropharyngeal tonsils, were isolated and cultured. The epithelial character of the cells from the dorsal soft palate was then assessed by immunofluorescence. The FMDV-sensitivity of these cells was assessed after monolayer infection with FMDV O/FRA/1/2001 Clone 2.2. These cells were also grown in multilayers at the air-liquid interface to mimic a stratified epithelium susceptible to FMDV infection. Consistent with what has been shown in vivo in pigs, our study showed no evidence of persistence of FMDV in either the monolayer or multilayer model, with no infectious virus detected 28 days after infection. The development of such a model opens up new possibilities for the study and diagnosis of FMDV in porcine cells

Swallowing dysfunction among older people in short-term care : prevalence, effect of intervention, and risk of mortality

Objectives: Swallowing dysfunction (dysphagia) is a common, but often neglected condition among geriatric patients that can cause severe complications such as malnutrition, aspiration pneumonia and death. The aims of this thesis were to (i) describe the study design and method of the multidisciplinary and multicenter project SOFIA (Swallowing function, Oral health, and Food Intake in old Age), (ii) study the prevalence of and the relationship between swallowing dysfunction and risk of undernutrition among older individuals in short-term care, (iii) study the effect of oral neuromuscular training on swallowing dysfunction among older individuals, and (iv) to investigate the association between poor oral health, swallowing dysfunction and mortality. Methods: This thesis includes four original papers that are all part of the SOFIA project. Paper Iis the study protocol. In total, 391 individuals aged 65 or older, from 36 short-term care units were included in the project. At baseline the participants’ status regarding swallowing function (assessed with the Timed Water Swallow Test, TWST), oral health (using the Revised Oral Assessment Guide, ROAG) and nutrition (assessed with the Minimal Eating Observation and Nutrition Form-version II, MEONF-II) were assessed and collected by calibrated professionals. Clinical data were also collected. Paper IIwas a cross-sectional study where the baseline assessments of the participants’ swallowing function and nutritional status were obtained and the relationship analyzed. Paper IIIwas a cluster randomized, controlled trial (cRCT) that included 116 participants identified with swallowing dysfunction in paper II. These participants were randomly assigned to either usual care (control group) or oral neuromuscular training (intervention group). All participants were assessed at baseline, after five weeks’ training and six months after end-of-treatment, regarding swallowing function and swallowing-related quality of life (QOL). Paper IVwas a prospective cohort study where all participants were followed-up 1-year after inclusion to investigate risk factors for mortality by analysis of the associations between swallowing dysfunction, poor oral health, and 1-year survival.  Results: Paper II:The median age of the 391 participants was 84 years (Interquartile range [IQR] 11) and 209 (53%) were females. In total, 248 of the 385 (64%) participants showed swallowing dysfunction, and risk of undernutrition was observed in 91 of 390 (23%) participants. The adjusted logistics regression model revealed that participants with swallowing dysfunction had significantly higher odds of undernutrition than those with normal swallowing (Odds ratio [OR]: 1.74, 95% Confidence interval [CI] 1.04 to 2.92, P=0.034).Paper III: At end-of-treatment, a linear mixed model showed significant between-group differences of changes in swallowing efficacy between baseline and after completed treatment period (Ratio 1.60, 95% CI 1.15 to 2.29, P=0.007); indicating a 60% higher swallowing efficacy in the intervention group compared with the control group. Paper IV: A mixed effects Cox model showed that swallowing dysfunction and poor oral health were both independently associated with 1-year mortality (adjusted Hazard Ratio [aHR]: 1.67, 95% CI 1.02 to 2.75,P=0.041 and aHR: 1.98, 95% CI 1.07 to 3.65, P=0.029, respectively). In addition, swallowing dysfunction and poor oral health in combination predicted the highest mortality rate (35%, P<0.001). Conclusion: Swallowing dysfunction is highly prevalent and a risk factor for undernutrition among older people in short-term care. Oral neuromuscular training improves swallowing dysfunction and is thus a promising method of swallowing rehabilitation for older people with impaired swallowing. Swallowing dysfunction and poor oral health are independent risk factors for 1-year morality among older people in short-term care. Therefore, systematic screening and intervention to improve swallowing dysfunction and poor oral health are important to achieve healthy aging and to prevent undernutrition and early death.Sväljningsdysfunktion (ibland benämnt dysfagi) är ett vanligt, men ofta förbisett tillstånd bland äldre individer. Dysfunktion vid sväljning kan orsaka svåra komplikationer såsom näringsbrist, viktförlust, lunginflammation och för tidig död. Enkla behandlingsmetoder vid sväljsvårigheter saknas och är efterfrågade. Neuromuskulär behandling med munskärm innebär stimulering av muskler och nerver i ansiktet, munnen och svalget, och har nyligen visats vara effektivt vid behandling av sväljsvårigheter. Det saknas dock kunskap om metoden fungerar bland äldre personer. Syftet med avhandlingen är att i) beskriva metoderna och designen i det multidisciplinära, multicenter projektet SOFIA (Swallowing function, Oral health, and Food Intake in old Age), ii) beskriva förekomsten av och analysera samband mellan sväljningsdysfunktion och risk för undernäring bland äldre som vistas på korttidsboende, iii) undersöka utfallet av en ny träningsmetod med munskärm för äldre individer med sväljsvårigheter samt iv) analysera dödlighet relaterat till dålig munhälsa och sväljningsdysfunktion. Delstudie 1 är en metodstudie där det övergripande SOFIA-projektet beskrivs. Totalt inkluderades 391 äldre individer från 36 korttidsboende från fem regioner (län) i Sverige som uppfyllde inklusionskriterierna: 65 år eller äldre, vistats på korttidsboende minst tre dagar, förstår svenska och kan delta i de kliniska undersökningarna. Individer i livets slutskede eller med måttlig till svår kognitiv svikt exkluderades. Efter inklusion i SOFIA-projektet bedömdes samtliga deltagares status avseende sväljfunktion, risk för undernäring, munhälsa och delaktighet i sin allmänna dagliga livsföring (ADL). Kliniska och socioekonomiska data samlades också in för varje deltagare. Delstudie 2 var en deskriptiv tvärsnittsstudie, där förekomsten av sväljningsdysfunktion och risk för undernäring undersöktes bland de äldre. Vidare undersöktes om sväljningsdysfunktion ökade risken för undernäring. I Delstudie 3 erbjöds de äldre som uppvisade sväljningsdysfunktion vid basbedömningen deltagande i en behandlingsstudie. De som tackad ja till deltagande randomiserades till fem veckors munskärmsträning eller till rutinvård utan munskärm. Varje deltagares sväljfunktion och sväljrelaterad livskvalitet bedömdes före och efter munskärmsträningen samt sex månader efter avslutad intervention. Delstudie 4 var en longitudinell kohortstudie. Ett år efter första bedömningen av deltagarna gjordes ett utdrag från dödsregistret och relationen mellan dålig munhälsa och sväljningsdysfunktion analyserades med överlevnad som utfall. Resultaten visade att nästan två tredjedelar (64%) av de äldre i korttidsboende har en sväljningsdysfunktion och var fjärde (23%) löper risk för undernäring (delstudie 2). Sväljningsdysfunktion är en riskfaktor för undernäring (delstudie 2). De äldre som tränade med munskärm i fem veckor visade sig förbättra sväljfunktionen signifikant jämfört med kontrollerna (delstudie 3). Både sväljningsdysfunktion och dålig munhälsa, oberoende av varandra, visade sig ge högre risk för dödlighet inom ett år bland äldre på korttidsboende (delstudie 4). Även att ha lågt kroppsmasseindex (BMI) visades vara en riskfaktor för tidig död. Resultaten i denna avhandling visar att både sväljningsdysfunktion och dålig munhälsa medför en högre risk för dödlighet bland äldre som vistas på korttidsboende. Detta ger starkt stöd för att diagnostik av och omvårdnad vid sväljsvårigheter och dålig munhälsa behöver förbättras bland äldre i korttidsboende. Vidare visar resultaten att sväljningsdysfunktion och risk för undernäring är vanligt förekommande och att munsskärmsträning är en ny potentiell behandlingsmetod vid nedsatt sväljfunktion bland äldre. Implementering av munskärmsträning vid sväljningsdysfunktion kan minska riskerna för näringsbrist, uttorkning och lungkomplikationer samt för tidig död

Swallowing dysfunction among older people in short-term care : prevalence, effect of intervention, and risk of mortality

Objectives: Swallowing dysfunction (dysphagia) is a common, but often neglected condition among geriatric patients that can cause severe complications such as malnutrition, aspiration pneumonia and death. The aims of this thesis were to (i) describe the study design and method of the multidisciplinary and multicenter project SOFIA (Swallowing function, Oral health, and Food Intake in old Age), (ii) study the prevalence of and the relationship between swallowing dysfunction and risk of undernutrition among older individuals in short-term care, (iii) study the effect of oral neuromuscular training on swallowing dysfunction among older individuals, and (iv) to investigate the association between poor oral health, swallowing dysfunction and mortality. Methods: This thesis includes four original papers that are all part of the SOFIA project. Paper Iis the study protocol. In total, 391 individuals aged 65 or older, from 36 short-term care units were included in the project. At baseline the participants’ status regarding swallowing function (assessed with the Timed Water Swallow Test, TWST), oral health (using the Revised Oral Assessment Guide, ROAG) and nutrition (assessed with the Minimal Eating Observation and Nutrition Form-version II, MEONF-II) were assessed and collected by calibrated professionals. Clinical data were also collected. Paper IIwas a cross-sectional study where the baseline assessments of the participants’ swallowing function and nutritional status were obtained and the relationship analyzed. Paper IIIwas a cluster randomized, controlled trial (cRCT) that included 116 participants identified with swallowing dysfunction in paper II. These participants were randomly assigned to either usual care (control group) or oral neuromuscular training (intervention group). All participants were assessed at baseline, after five weeks’ training and six months after end-of-treatment, regarding swallowing function and swallowing-related quality of life (QOL). Paper IVwas a prospective cohort study where all participants were followed-up 1-year after inclusion to investigate risk factors for mortality by analysis of the associations between swallowing dysfunction, poor oral health, and 1-year survival.  Results: Paper II:The median age of the 391 participants was 84 years (Interquartile range [IQR] 11) and 209 (53%) were females. In total, 248 of the 385 (64%) participants showed swallowing dysfunction, and risk of undernutrition was observed in 91 of 390 (23%) participants. The adjusted logistics regression model revealed that participants with swallowing dysfunction had significantly higher odds of undernutrition than those with normal swallowing (Odds ratio [OR]: 1.74, 95% Confidence interval [CI] 1.04 to 2.92, P=0.034).Paper III: At end-of-treatment, a linear mixed model showed significant between-group differences of changes in swallowing efficacy between baseline and after completed treatment period (Ratio 1.60, 95% CI 1.15 to 2.29, P=0.007); indicating a 60% higher swallowing efficacy in the intervention group compared with the control group. Paper IV: A mixed effects Cox model showed that swallowing dysfunction and poor oral health were both independently associated with 1-year mortality (adjusted Hazard Ratio [aHR]: 1.67, 95% CI 1.02 to 2.75,P=0.041 and aHR: 1.98, 95% CI 1.07 to 3.65, P=0.029, respectively). In addition, swallowing dysfunction and poor oral health in combination predicted the highest mortality rate (35%, P<0.001). Conclusion: Swallowing dysfunction is highly prevalent and a risk factor for undernutrition among older people in short-term care. Oral neuromuscular training improves swallowing dysfunction and is thus a promising method of swallowing rehabilitation for older people with impaired swallowing. Swallowing dysfunction and poor oral health are independent risk factors for 1-year morality among older people in short-term care. Therefore, systematic screening and intervention to improve swallowing dysfunction and poor oral health are important to achieve healthy aging and to prevent undernutrition and early death.Sväljningsdysfunktion (ibland benämnt dysfagi) är ett vanligt, men ofta förbisett tillstånd bland äldre individer. Dysfunktion vid sväljning kan orsaka svåra komplikationer såsom näringsbrist, viktförlust, lunginflammation och för tidig död. Enkla behandlingsmetoder vid sväljsvårigheter saknas och är efterfrågade. Neuromuskulär behandling med munskärm innebär stimulering av muskler och nerver i ansiktet, munnen och svalget, och har nyligen visats vara effektivt vid behandling av sväljsvårigheter. Det saknas dock kunskap om metoden fungerar bland äldre personer. Syftet med avhandlingen är att i) beskriva metoderna och designen i det multidisciplinära, multicenter projektet SOFIA (Swallowing function, Oral health, and Food Intake in old Age), ii) beskriva förekomsten av och analysera samband mellan sväljningsdysfunktion och risk för undernäring bland äldre som vistas på korttidsboende, iii) undersöka utfallet av en ny träningsmetod med munskärm för äldre individer med sväljsvårigheter samt iv) analysera dödlighet relaterat till dålig munhälsa och sväljningsdysfunktion. Delstudie 1 är en metodstudie där det övergripande SOFIA-projektet beskrivs. Totalt inkluderades 391 äldre individer från 36 korttidsboende från fem regioner (län) i Sverige som uppfyllde inklusionskriterierna: 65 år eller äldre, vistats på korttidsboende minst tre dagar, förstår svenska och kan delta i de kliniska undersökningarna. Individer i livets slutskede eller med måttlig till svår kognitiv svikt exkluderades. Efter inklusion i SOFIA-projektet bedömdes samtliga deltagares status avseende sväljfunktion, risk för undernäring, munhälsa och delaktighet i sin allmänna dagliga livsföring (ADL). Kliniska och socioekonomiska data samlades också in för varje deltagare. Delstudie 2 var en deskriptiv tvärsnittsstudie, där förekomsten av sväljningsdysfunktion och risk för undernäring undersöktes bland de äldre. Vidare undersöktes om sväljningsdysfunktion ökade risken för undernäring. I Delstudie 3 erbjöds de äldre som uppvisade sväljningsdysfunktion vid basbedömningen deltagande i en behandlingsstudie. De som tackad ja till deltagande randomiserades till fem veckors munskärmsträning eller till rutinvård utan munskärm. Varje deltagares sväljfunktion och sväljrelaterad livskvalitet bedömdes före och efter munskärmsträningen samt sex månader efter avslutad intervention. Delstudie 4 var en longitudinell kohortstudie. Ett år efter första bedömningen av deltagarna gjordes ett utdrag från dödsregistret och relationen mellan dålig munhälsa och sväljningsdysfunktion analyserades med överlevnad som utfall. Resultaten visade att nästan två tredjedelar (64%) av de äldre i korttidsboende har en sväljningsdysfunktion och var fjärde (23%) löper risk för undernäring (delstudie 2). Sväljningsdysfunktion är en riskfaktor för undernäring (delstudie 2). De äldre som tränade med munskärm i fem veckor visade sig förbättra sväljfunktionen signifikant jämfört med kontrollerna (delstudie 3). Både sväljningsdysfunktion och dålig munhälsa, oberoende av varandra, visade sig ge högre risk för dödlighet inom ett år bland äldre på korttidsboende (delstudie 4). Även att ha lågt kroppsmasseindex (BMI) visades vara en riskfaktor för tidig död. Resultaten i denna avhandling visar att både sväljningsdysfunktion och dålig munhälsa medför en högre risk för dödlighet bland äldre som vistas på korttidsboende. Detta ger starkt stöd för att diagnostik av och omvårdnad vid sväljsvårigheter och dålig munhälsa behöver förbättras bland äldre i korttidsboende. Vidare visar resultaten att sväljningsdysfunktion och risk för undernäring är vanligt förekommande och att munsskärmsträning är en ny potentiell behandlingsmetod vid nedsatt sväljfunktion bland äldre. Implementering av munskärmsträning vid sväljningsdysfunktion kan minska riskerna för näringsbrist, uttorkning och lungkomplikationer samt för tidig död

Factors associated with malnutrition among older people in Swedish short-term care : Poor oral health, dysphagia and mortality

Objectives: To investigate the relationship between malnutrition and potential contributing factors such as poor oral health, dysphagia and mortality among older people in short-term care. Methods: This cross-sectional study is a part of the multidisciplinary multicentre project SOFIA (Swallowing function, Oral health and Food Intake in old Age), which includes older people (≥65 years) in 36 short-term care units in five regions of Sweden. Nutritional status was measured with version II of the Minimal Eating Observation and Nutrition Form (MEONF-II), oral health with the Revised Oral Assessment Guide (ROAG), dysphagia with a water swallow test, and the mortality rate was followed for 1 year. Data were analysed using descriptive analysis and logistic regression models to calculate odds ratios for the association between malnutrition and these factors. Results: Among the 391 participants, the median age was 84 years and 53.3% were women. Mortality rate was 25.1% within 1 year in the total group, and was higher among malnourished participants than among their well-nourished counterparts. Severe dysphagia (OR: 6.51, 95% CI: 2.40–17.68), poor oral health (OR: 5.73, 95% CI: 2.33–14.09) and female gender (OR: 2.2, 95% CI: 1.24–3.93) were independently associated with malnutrition. Conclusion: Mortality rate was higher among malnourished people than those who were well nourished. Severe dysphagia, poor oral health and female gender was predictors of malnutrition among older people in short-term care. These health risks should be given more attention in short-term care with early identification

The Timed Water Swallow Test (TWST) : normative data on swallowing capacity for healthy people aged 60 years and older

Purpose: To provide normative data on swallowing capacity (mL/s) in people older than 60 years using the Timed Water Swallow Test (TWST), stratified by sex. Intra- and inter-rater reliability for swallowing time in TWST was further investigated. Method: A total of 165 participants, aged 60 years and above, were included in the study. The time taken to consume 150 mL of tap water and the swallowing capacity (mL/s) was observed in a clinical context using the TWST. Video recordings of the performances were collected for 118 of the 165 participants for inter-rater reliability testing, of which a random set of 25 performances were assessed for intra-rater reliability. Analysis of the agreement between TWST rated by an in-person clinician and rated from a video recording was further evaluated. Result: There were significant age and sex effects observed for swallowing capacity. The average reduction in swallowing capacity in the investigated age range (60-92 years) was 8.8 and 7.3 mL/s for women and men respectively. The results showed high inter-and intra-rater reliability and agreement between the clinical assessment and the video recording. Conclusion: The presented measurements indicate a clear effect of age on swallowing capacity and that women may be expected to have lower capacity scores than men when tested using TWST. The provided norms can be used as reference points in the clinical identification of people at risk of dysphagia in the older population

Oropharyngeal dysphagia and associated factors among individuals living in nursing homes in northern Sweden in 2007 and 2013

Background: Swallowing difficulties in the oral cavity or pharynx (i.e., oropharyngeal dysphagia) are a common problem in the aging population, which may result in severe consequences, such as malnutrition, aspiration pneumonia, and mortality. Identifying oropharyngeal dysphagia and its associated factors is essential for establishing better healthcare policies in nursing homes. In this study, we aimed to describe the oropharyngeal dysphagia prevalence among nursing home residents, and to investigate the association between dysphagia and potentially related factors in a large survey of nursing home residents in Sweden, including individuals with various degrees of cognitive impairment. A secondary aim was to compare findings between years on oropharyngeal dysphagia and its associated factors. Methods: This study is based on two cross-sectional surveys performed in 2007 and 2013, including 4,995 individuals living in nursing homes in the Region of Västerbotten, Sweden. Data were collected from caregivers’ reports regarding swallowing ability, nutritional status, chewing ability, and other baseline characteristics, such as cognitive function and activity of daily living (ADL). Data were analyzed using logistic regression models to calculate the odds of the association between oropharyngeal dysphagia and associated factors. Results: Oropharyngeal dysphagia was reported in 14.9% (95% CI: 13.9–16.0) of the nursing home residents. An adjusted model revealed that oropharyngeal dysphagia was associated by severe cognitive impairment (OR: 1.56, 95% CI: 1.14–2.12) and ADL independence (OR: 0.81 95% CI: 1.82–2.66) among nursing home residents. We also identified the following as independently associated factors of dysphagia: reduced nutritional status (OR: 1.84, 95% CI: 1.49–2.27), artificial nutrition (OR: 6.33, 95% CI: 2.73–14.71), and clinical signs of aspiration (OR: 10.89, 95% CI: 8.40–14.12). Conclusions: Oropharyngeal dysphagia was reported among approximately 15% nursing home residents and was associated with cognitive impairment and ADL capability. Furthermore, reduced nutritional status and artificial nutrition were also associated with oropharyngeal dysphagia. Implementing routine protocols in nursing homes may help detect oropharyngeal dysphagia and manage oropharyngeal dysphagia among residents

The Test of Masticating and Swallowing Solids (TOMASS) : Normative data for two crackers available in the Scandinavian and international markets

Purpose: To establish normative data of crackers common in the Scandinavian and international markets for use in the Test of Masticating and Swallowing Solids (TOMASS), and to investigate possible sex and age effects on masticatory performances. Method: 234 healthy participants (>20 years of age) were asked to either ingest the Göteborgskex Guld Marie™ cracker (n = 234) or to ingest both a Guld Marie cracker and a Tuc Original™ cracker (n = 115). Quantifiable measures of masticatory performance (number of bites, number of chewing cycles, number of swallows, and total time) were observed during TOMASS for each participant, directly on-site or by video recording. Result: There were no significant differences in masticatory performances between the crackers. Significant age effects were observed for all masticatory measurements, except for the number of swallows. The results showed insufficient support for an effect of sex, and that results obtained on-site and from video recordings were highly correlated. Conclusion: These findings suggest that similar masticatory performance is to be expected when performing TOMASS using the evaluated crackers. The age of the participant affects TOMASS performance, but the effect of sex is considerably smaller

Effects of oral neuromuscular training on swallowing dysfunction among older people in intermediate care : a cluster randomized, controlled trial

Objectives: this prospective, cluster randomised, controlled trial investigated the effect of oral neuromuscular training among older people in intermediate care with impaired swallowing. Methods: older people (≥65 years) with swallowing dysfunction were cluster randomised according to care units for 5 weeks of neuromuscular training of the orofacial and pharyngeal muscles or usual care. The primary endpoint was the change in swallowing rate (assessed with a timed water swallow test) from baseline to the end-of-treatment and 6 months post-treatment. The secondary endpoints were changes in signs of aspiration during the water swallow test, and swallowing-related quality of life (QOL). An intention-to-treat principle was followed, and mixed-effects models were used for data analysis with the clustered study design as a random factor. Results: in total, 385 participants from 36 intermediate care units were screened, and 116 participants were randomly assigned to oral neuromuscular training (intervention; n = 49) or usual care (controls; n = 67). At the end of treatment, the geometric mean of the swallowing rate in the intervention group had significantly improved 60% more than that of controls (P = 0.007). At 6 months post-treatment, the swallowing rate of the intervention group remained significantly better (P = 0.031). Signs of aspiration also significantly reduced in the intervention group compared with controls (P = 0.01). No significant between-group differences were found for swallowing-related QOL. Conclusions: oral neuromuscular training is a new promising swallowing rehabilitation method among older people in intermediate care with impaired swallowing. Trial registration: ClinicalTrials.gov: NCT02825927.Originally included in thesis in manuscript form.</p

Speech intelligibility in Parkinson's disease patients with zona incerta deep brain stimulation

Objectives To investigate the effects of l-dopa (Levodopa) and cZi-DBS (deep brain stimulation in caudal zona incerta) on spontaneous speech intelligibility in patients with PD (Parkinson's disease). Materials and Methods Spontaneous utterances were extracted from anechoic recordings from 11 patients with PD preoperatively (off and on l-dopa medication) and 6 and 12 months post bilateral cZi-DBS operation (off and on stimulation, with simultaneous l-dopa medication). Background noise with an amplitude corresponding to a clinical setting was added to the recordings. Intelligibility was assessed through a transcription task performed by 41 listeners in a randomized and blinded procedure. Results A group-level worsening in spontaneous speech intelligibility was observed on cZi stimulation compared to off 6 months postoperatively (8 adverse, 1 positive, 2 no change). Twelve months postoperatively, adverse effects of cZi-DBS were not frequently observed (2 positive, 3 adverse, 6 no change). l-dopa administered preoperatively as part of the evaluation for DBS operation provided the overall best treatment outcome (1 adverse, 4 positive, 6 no change). Conclusions cZi-DBS was shown to have smaller negative effects when evaluated from spontaneous speech compared to speech effects reported previously. The previously reported reduction in word-level intelligibility 12 months postoperatively was not transferred to spontaneous speech for most patients. Reduced intelligibility due to cZi stimulation was much more prominent 6 months postoperatively than at 12 months