An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

Motor Performance During Sensorimotor Training for Airway Protection in Parkinson's Disease.

INTRODUCTION: Cough dysfunction is highly prevalent in Parkinson's disease (PD) and associated with pneumonia, a leading cause of death. Although research suggests that cough can be volitionally upregulated, patterns of improvements that occur during cough skill training and potential correlates remain unexamined. Therefore, we sought to characterize changes to peak flow during cough skill training, examine whether early variability predicted motor performance trajectories during treatment, and explore the relationship between peak flow during cough skill training and motor learning on a similar but untrained task (i.e., reflex cough testing). METHOD: This secondary analysis of treatment data from a randomized controlled trial included 28 individuals with PD who participated in five sessions of sensorimotor training for airway protection (smTAP). During this novel cough skill training, participants completed 25 repetitions of coughs targeting peak flow 25% above their baseline. Reflex and voluntary cough testing was performed pre- and posttreatment. Bayesian multilevel growth curve models provided group and individual-level estimates of peak flow during training. RESULTS: The magnitude and consistency of peak flow increased during cough skill training. Variability in peak flow during the first treatment session was associated with greater improvements to peak flow in later sessions. There was no relationship between changes to peak flow during cough skill training and motor learning. CONCLUSIONS: Individuals with PD improved the strength and variability of cough peak flow during cough skill training. These findings provide a clinically relevant characterization of motor performance during cough skill training and lend insight into potential correlates to guide future treatment paradigms.

Spinal cord stimulation for gait disturbances in Parkinson's disease.

INTRODUCTION: Gait disturbances are a major contributor to the disability associated with Parkinson's disease. Although pharmacologic therapies and deep brain stimulation improve most motor parkinsonian features, their effects on gait are highly variable. Spinal cord stimulation, typically used for the treatment of chronic pain, has emerged as a potential therapeutic approach to improve gait disturbances in Parkinson's disease. AREAS COVERED: The authors review the available evidence on the effects of spinal cord stimulation in patients with Parkinson's disease, targeting primarily gait abnormalities. They also discuss possible mechanisms, safety, and methodological implications for future clinical trials. This systematic review of originally published articles in English language was performed using The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).

Future directions in psychiatric neurosurgery: Proceedings of the 2022 American Society for Stereotactic and Functional Neurosurgery meeting on surgical neuromodulation for psychiatric disorders.

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. DESIGN: The ASSFN convened a meeting on June 3, 2022 in Atlanta, Georgia and included leaders from the fields of neurology, neurosurgery, and psychiatry along with colleagues from industry, government, ethics, and law. The goal was to review the current state of the field, assess for advances or setbacks in the interim six years, and suggest a future path forward. The participants focused on five areas of interest: interdisciplinary engagement, regulatory pathways and trial design, disease biomarkers, ethics of psychiatric surgery, and resource allocation/prioritization. The proceedings are summarized here. CONCLUSION: The field of surgical psychiatry has made significant progress since our last expert meeting. Although weakness and threats to the development of novel surgical therapies exist, the identified strengths and opportunities promise to move the field through methodically rigorous and biologically-based approaches. The experts agree that ethics, law, patient engagement, and multidisciplinary teams will be critical to any potential growth in this area.

Quantifying Impairments in Swallowing Safety and Efficiency in Progressive Supranuclear Palsy and Parkinson's Disease.

Dysphagia is a largely inevitable symptom in both progressive supranuclear palsy (PSP) and Parkinson's disease (PD). To date, comparative studies in these diseases have failed to detect differences in the severity of impairments in swallowing safety or efficiency, potentially due to small sample sizes and outcome measures with low sensitivity. Therefore, this study sought to address these limitations by using novel measurement methodology to comprehensively compare swallowing safety and efficiency impairments between these populations in order to better understand whether differences may exist and guide clinical management. Twenty-four participants with PSP and 24 with PD were matched for disease duration and completed flexible endoscopic evaluations of swallowing. A visual analog scale and penetration-aspiration scale quantified swallowing safety and efficiency. Bayesian multilevel models compared the frequency, severity, and variability of swallowing impairments. Individuals with PSP demonstrated greater impairments in swallowing safety, including deeper and more variable airway invasion and more frequent vocal fold and subglottic residue. Swallowing efficiency was also more impaired among individuals with PSP, including more frequent hypopharyngeal residue (with solids) and more severe residue in the oropharynx (with thin liquids and solids) and hypopharynx (with thin liquids). When airway or pharyngeal residue was present, similar within-subject variability of the amount of residue was appreciated across anatomic landmarks. This is the first study comparing the frequency, severity, and variability of swallowing impairments between PSP and PD populations. Our findings demonstrate more pronounced impairments in swallowing safety and efficiency for PSP compared to PD. These findings provide a clinically relevant characterization of swallowing measures using novel methodological and statistical approaches attempting to resolve some limitations of prior studies.

Rehabilitating Cough Dysfunction in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Disorders of airway protection (cough and swallowing) are pervasive in Parkinson's disease (PD) resulting in a high incidence of aspiration pneumonia and death. However, there are no randomized controlled trials comparing strength and skill-based approaches to improve airway protection in PD. OBJECTIVES: The aim of this study was to compare expiratory muscle strength training (EMST) and sensorimotor training for airway protection (smTAP) to improve cough-related outcomes in people with PD. METHODS: Participants with PD and dysphagia were recruited for this prospective phase II randomized-blinded controlled clinical trial. Participants completed baseline assessment, 5 weeks of EMST or smTAP, and a post-training assessment. Primary outcome measures included maximum expiratory pressure (MEP) and voluntary cough peak expiratory flow rate (PEFR). Mixed effects models were used to assess the effects of EMST and smTAP on outcomes. RESULTS: A total of 65 participants received either EMST (n = 34) or smTAP (n = 31). MEP improved from pre- to post-treatment for smTAP (P < 0.001, d = 0.19) and EMST (P < 0.001, d = 0.53). Voluntary PEFR increased from pre- to post-treatment for smTAP (P < 0.001, d = 0.19) and EMST (P < 0.001, d = 0.06). Moreover, reflex cough PEFR (P < 0.001, d = 0.64), reflex cough expired volume (P < 0.001, d = 0.74), and urge to cough (P = 0.018, OR = 2.70) improved for the smTAP group but not for the EMST group. CONCLUSIONS: This clinical trial confirmed the efficacy of smTAP to improve reflex and voluntary cough function, above and beyond EMST, the current gold standard. © 2022 International Parkinson and Movement Disorder Society.

Telehealth for Assessing and Managing Tardive Dyskinesia: Expert Insights from a Cross-Disciplinary Virtual Treatment Panel.

Introduction: Publications on the integration of telehealth in the care of patients with movement disorders are increasing, but little has been presented regarding its use in tardive dyskinesia (TD), a drug-induced movement disorder associated with prolonged exposure to dopamine receptor blocking agents. This study was conducted to address that knowledge gap, based on insights from a panel of TD experts. Methods: In 2020, six neurologists, three psychiatrists, and three psychiatric nurse practitioners participated in individual semistructured interviews about in-person and virtual TD assessment and management in their practices. Two virtual roundtables were then conducted to consolidate findings from these interviews. Results: The panel agreed that despite the challenges of virtual TD assessment (e.g., technology issues, difficulty observing entire body, inability to conduct thorough neurological examinations), telehealth can offer benefits (e.g., fewer missed appointments, reduced time/cost, easier access to family/caregiver feedback). The panel also agreed that telehealth should be combined with periodic in-person visits, and they recommended an in-person TD assessment within 6 months before the first virtual visit and at least one in-person assessment every 6 months thereafter. Additional best practices for TD telehealth included implementing video, involving family/caregivers, and providing preappointment instructions to help patients prepare their technology and environment. Conclusions: Telehealth is not a substitute for in-person visits but can be a helpful complement to in-person clinical care. Clinicians can optimize virtual visits in patients at risk of TD by using targeted questions to identify TD and evaluate its impact and by providing education about approved TD treatments.

Association of clinical outcomes and connectivity in awake versus asleep deep brain stimulation for Parkinson disease.

OBJECTIVE: Deep brain stimulation (DBS) for Parkinson disease (PD) is traditionally performed with awake intraoperative testing and/or microelectrode recording. Recently, however, the procedure has been increasingly performed under general anesthesia with image-based verification. The authors sought to compare structural and functional networks engaged by awake and asleep PD-DBS of the subthalamic nucleus (STN) and correlate them with clinical outcomes. METHODS: Levodopa equivalent daily dose (LEDD), pre- and postoperative motor scores on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III), and total electrical energy delivered (TEED) at 6 months were retroactively assessed in patients with PD who received implants of bilateral DBS leads. In subset analysis, implanted electrodes were reconstructed using the Lead-DBS toolbox. Volumes of tissue activated (VTAs) were used as seed points in group volumetric and connectivity analysis. RESULTS: The clinical courses of 122 patients (52 asleep, 70 awake) were reviewed. Operating room and procedure times were significantly shorter in asleep cases. LEDD reduction, MDS-UPDRS III score improvement, and TEED at the 6-month follow-up did not differ between groups. In subset analysis (n = 40), proximity of active contact, VTA overlap, and desired network fiber counts with motor STN correlated with lower DBS energy requirement and improved motor scores. Discriminative structural fiber tracts involving supplementary motor area, thalamus, and brainstem were associated with optimal clinical improvement. Areas of highest structural and functional connectivity with VTAs did not significantly differ between the two groups. CONCLUSIONS: Compared to awake STN DBS, asleep procedures can achieve similarly optimal targeting-based on clinical outcomes, electrode placement, and connectivity estimates-in more efficient procedures and shorter operating room times.

Where Do Parkinson's Disease Patients Look While Walking?

BACKGROUND: Parkinson's disease (PD) is associated with gait and visuomotor abnormalities, but it is not clear where PD patients look during ambulation. OBJECTIVE: We sought to characterize the visual areas of interest explored by PD patients, with and without freezing of gait (FOG), compared to healthy volunteers (HVs). METHODS: Using an eye-tracking device, we compared visual fixation patterns in 17 HVs and 18 PD patients, with and without FOG, during an ambulatory and a nonambulatory, computer-based task. RESULTS: During ambulation, PD patients with FOG fixated more on proximal areas of the ground and less on the target destination. PD patients without FOG displayed a fixation pattern more similar to that of HVs. Similar patterns were observed during the nonambulatory, computer-based task. CONCLUSIONS: Our findings suggest increased dependence on visual feedback from nearby areas in the environment in PD patients with FOG, even in the absence of motor demands. © 2022 International Parkinson and Movement Disorder Society.

COVID-19 manifestations in people with Parkinson's disease: a USA cohort.

BACKGROUND: With the explosion of COVID-19 globally, it was unclear if people with Parkinson's disease (PD) were at increased risk for severe manifestations or negative outcomes. OBJECTIVES: To report on people with PD who had suspected or confirmed COVID-19 to understand how COVID-19 manifested in PD patients. METHODS: We surveyed PD patients who reported COVID-19 to their Movement Disorders specialists at Columbia University Irving Medical Center and respondents from an online survey administered by the Parkinson's Foundation that assessed COVID-19 symptoms, general clinical outcomes and changes in motor and non-motor PD symptoms. RESULTS: Forty-six participants with PD and COVID-19 were enrolled. Similar to the general population, the manifestations of COVID-19 among people with PD were heterogeneous ranging from asymptomatic carriers (1/46) to death (6/46). The most commonly reported COVID-19 symptoms were fever/chills, fatigue, cough, weight loss, and muscle pain. Worsening and new onset of motor and non-motor PD symptoms during COVID-19 illness were also reported, including dyskinesia, rigidity, balance disturbances, anxiety, depression, and insomnia. CONCLUSION: We did not find sufficient evidence that PD is an independent risk factor for severe COVID-19 and death. Larger studies with controls are required to understand this further. Longitudinal follow-up of these participants will allow for observation of possible long-term effects of COVID-19 in PD patients.

Cerebellar Oscillations in Familial and Sporadic Essential Tremor.

Enhanced cerebellar oscillations have recently been identified in essential tremor (ET) patients as a key pathophysiological change. Since ET is considered a heterogeneous group of diseases, we investigated whether cerebellar oscillations differ in ET subtypes (familial vs. sporadic). This study aims to determine cerebellar physiology in familial and sporadic ET. Using surface electroencephalogram, we studied cerebellar physiology in 40 ET cases (n = 22 familial and n = 18 sporadic) and 20 age-matched controls. Both familial and sporadic ET cases had an increase in the intensity of cerebellar oscillations when compared to controls. Interestingly, cerebellar oscillations correlated with tremor severity in familial ET but not in sporadic ET. Our study demonstrated that ET cases have enhanced cerebellar oscillations, and the different relationships between cerebellar oscillations and tremor severity in familial and sporadic ET suggest diverse cerebellar pathophysiology.

Immediate Effects of Sensorimotor Training in Airway Protection (smTAP) on Cough Outcomes in Progressive Supranuclear Palsy: A Feasibility Study.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by a high prevalence of dysphagia, cough dysfunction, and resultant aspiration pneumonia. Sensorimotor cough function is important for airway clearance in people with dysphagia. Upregulation of cough has been demonstrated in healthy adults and Parkinson's disease; however, the feasibility of cough rehabilitation in PSP is unknown. We sought to assess feasibility by examining the immediate effects of a novel sensorimotor training in airway protection (smTAP) on upregulation of cough function in PSP. Fifteen individuals with PSP enrolled in this study. Baseline voluntary and reflex cough testing were completed. During smTAP, participants were presented with subthreshold capsaicin and instructed to cough with sufficient intensity to hit a target line (set 25% above baseline reflex peak cough flow) via cough airflow visual biofeedback. Twenty-five repetitions were targeted within a single session. Wilcoxon signed-rank tests compared cough airflow measures between baseline voluntary cough testing, the initial five trials of smTAP, and final five trials. Mean peak expiratory flow rate (PEFR) significantly increased from initial to final smTAP trials (p < 0.001). Fourteen participants increased PEFR, with gains of more than 10% in 11 participants. Variability of PEFR (p = 0.01) and cough expired volume (p = 0.01) significantly decreased across smTAP trials. This study is the first to demonstrate the ability of people with PSP to immediately upregulate cough function, providing preliminary support for the feasibility of cough rehabilitation in this population with this novel treatment approach. Future research examining the effects of multiple sessions of smTAP on cough outcomes is warranted.

Case Report: Dual Target Deep Brain Stimulation With Externalized Programming for Post-traumatic Complex Movement Disorder.

Introduction: Movement disorders can be common, persistent, and debilitating sequelae of severe traumatic brain injury. Post-traumatic movement disorders are usually complex in nature, involving multiple phenomenological manifestations, and can be difficult to control with medical management alone. Deep brain stimulation (DBS) has been used to treat these challenging cases, but distorted brain anatomy secondary to trauma can complicate effective targeting. In such cases, use of diffusion tractography imaging and inpatient testing with externalized DBS leads can be beneficial in optimizing outcomes. Case Description: We present the case of a 42-year-old man with severe, disabling post-traumatic tremor who underwent bilateral, dual target DBS to the globus pallidus internus (GPi) and a combined ventral intermediate nucleus of the thalamus (Vim)/dentato-rubro-thalamic tracts (DRTT) target. DRTT fiber tracts were reconstructed preoperatively to assist in surgical targeting given the patient's distorted anatomy. Externalization and survey of the four leads extra-operatively with inpatient testing allowed for internalization of the leads that demonstrated benefit. Six months after surgery, the patient's tremor and dystonic burden had decreased by 67% in the performance sub-score of The Essential Tremor Rating Scale (TETRAS). Conclusion: A patient-tailored approach including target selection guided by individualized anatomy and tractography as well as extra-operative externalized lead interrogation was shown to be effective in optimizing clinical outcome in a patient with refractory post-traumatic tremor.

Using computerized spiral analysis to evaluate deep brain stimulation outcomes in Parkinson disease.

OBJECTIVE: To determine whether spiral analysis can monitor the effects of deep brain stimulation (DBS) in Parkinson disease (PD) and provide a window on clinical features that change post-operatively. Clinical evaluation after DBS is subjective and insensitive to small changes. Spiral analysis is a computerized test that quantifies kinematic, dynamic, and spatial aspects of spiral drawing. Validated computational indices are generated and correlate with a range of clinically relevant motor findings. These include measures of overall clinical severity (Severity), bradykinesia and rigidity (Smoothness), amount of tremor (Tremor), irregularity of drawing movements (Variability), and micrographia (Tightness). METHODS: We retrospectively evaluated the effect of subthalamic nucleus (STN) (n = 66) and ventral intermediate thalamus (Vim) (n = 10) DBS on spiral drawing in PD subjects using spiral analysis. Subjects freely drew ten spirals on plain paper with an inking pen on a graphics tablet. Five spiral indices (Severity, Smoothness, Tremor, Variability, Tightness) were calculated and compared pre- and post-operatively using Wilcoxon-rank sum tests, adjusting for multiple comparisons. RESULTS: Severity improved after STN and Vim DBS (p < 0.005). Smoothness (p < 0.01) and Tremor (p < 0.02) both improved after STN and Vim DBS. Variability improved only with Vim DBS. Neither STN nor Vim DBS significantly changed Tightness. CONCLUSIONS: All major spiral indices, except Tightness, improved after DBS. This suggests spiral analysis monitors DBS effects in PD and provides an objective window on relevant clinical features that change post-operatively. It may thus have utilization in clinical trials or investigations into the neural pathways altered by DBS. The lack of change in Tightness supports the notion that DBS does not improve micrographia.

Telemedicine and Deep brain stimulation - Current practices and recommendations.

The use of telemedicine in the management of chronic neurological conditions including movement disorders has expanded over time. In addition to enabling remote access to specialized care, telemedicine has also been shown to reduce caregiver burden and to improve patient satisfaction. With the COVID-19 pandemic, implementation of telehealth for patients with movement disorders, particularly those with more severe mobility issues, has increased rapidly. Although telemedicine care has been shown to be effective for patients with various movement disorders, its utilization for patients with device aided therapies such as deep brain stimulation (DBS) is limited due to challenges related to adjusting these devices remotely and to the lack of consensus recommendations for using telemedicine in this patient population. Thus, guidelines for telemedicine and DBS will assist clinicians on the appropriate implementation of telemedicine to provide care to DBS patients. Optimizing the use of telemedicine for DBS will expand this type of therapy to remote locations with limited access to programming expertise, and also reduce the need for patient travel. Telemedicine is particularly important during the ongoing pandemic due to infection risk and limited access to clinic visits. In this article we review the currently available and emerging strategies for telemedicine and remote care for DBS. We then outline common principles and recommendations for telemedicine care in patients with DBS, review patient selection and best practices. Finally, we briefly discuss the current state of reimbursement for DBS telemedicine visits.

Sensorimotor Cough Dysfunction Is Prevalent and Pervasive in Progressive Supranuclear Palsy.

BACKGROUND: Pneumonia, a leading cause of death in progressive supranuclear palsy (PSP), results from progressive and pervasive deficits of airway protection, including both cough and swallowing dysfunction. Cough protects the airway by expelling aspirate and may be an important therapeutic target to protect against pneumonia in the presence of dysphagia. However, cough has not been objectively characterized in PSP or compared to other common forms of parkinsonism, such as Parkinson's disease (PD). OBJECTIVE: The purpose of this study was to examine voluntary and reflex cough function in PSP, as compared to patients with PD matched for disease duration. METHODS: Twenty-six patients with PSP and 26 with PD completed voluntary and reflex cough testing via spirometry. Linear mixed effects models examined comparisons between groups and within cough types across cough sensory and motor outcomes. RESULTS: Patients with PSP demonstrated significantly reduced cough motor function compared to PD, specifically reduced peak expiratory flow rate (P < 0.001), cough expiratory volume (P < 0.001), and cough inspiratory volume (P = 0.008). Both groups showed similar reflex cough thresholds (P = 0.694), but PSP demonstrated an increased perception of cough stimuli (P = 0.041). CONCLUSIONS: These findings suggest that sensorimotor cough dysfunction is prevalent in PSP, and cough motor deficits, in particular, are worse in PSP than in PD. These deficits likely contribute to the pathogenesis of pneumonia in PSP. Therefore, cough should be integrated into assessments of airway protection and considered as a therapeutic target to potentially reduce adverse health events and improve quality of life in this population. © 2021 International Parkinson and Movement Disorder Society.

The impact of COVID-19 and social distancing on people with Parkinson's disease: a survey study.

As the COVID-19 pandemic continues to affect the international community, very little is known about its impact on the health and day-to-day activities of people with Parkinson's disease (PwPD). To better understand the emotional and behavioral consequences of the public health policies implemented to mitigate the spread of SARS-CoV-2 in PwPD, and to explore the factors contributing to accessing alternative health care mechanisms, such as telehealth, we administered an anonymous knowledge, attitude, and practice survey to PwPD and care partners, via the mailing lists of the Parkinson's Foundation and Columbia University Parkinson's Disease Center of Excellence with an average response rate of 19.3%. Sufficient information was provided by 1,342 PwPD to be included in the final analysis. Approximately half of respondents reported a negative change in PD symptoms, with 45-66% reporting mood disturbances. Telehealth use increased from 9.7% prior to the pandemic to 63.5% during the pandemic. Higher income and higher education were associated with telehealth use. Services were more often used for doctor's appointment than physical, occupational, speech, or mental health therapies. Almost half (46%) of PwPD preferred to continue using telehealth always or sometimes after the coronavirus outbreak had ended. Having received support/instruction for telehealth and having a care partner, friend, or family member to help them with the telehealth visit increased the likelihood of continuous use of telehealth after the pandemic ended. Taken together, PD symptoms and management practices were markedly affected by COVID-19. Given the observed demographic limitations of telehealth, expanding its implementation to include additional physical, occupational, psychological, and speech therapies, increasing support for telehealth, as well as reaching underserved (low income) populations is urgently required.

The Role of Vocal Fold Bowing on Cough and Swallowing Dysfunction in Progressive Supranuclear Palsy.

OBJECTIVES: Progressive supranuclear palsy (PSP) is a neurodegenerative disease which results in cough and swallowing dysfunction and aspiration pneumonia. Relationships among vocal fold atrophy, cough, and swallowing have been identified in related diseases, but remain unknown in PSP. This study examined: 1) the prevalence of vocal fold bowing in PSP, and 2) the influence of vocal fold bowing on cough and swallowing in PSP. STUDY DESIGN: Prospective Cohort Study. METHODS: Twenty-three participants with PSP completed instrumental assessments of cough and swallowing. Vocal fold bowing (BI) and swallowing safety (PAS) was assessed using flexible laryngoscopy. Measures of cough effectiveness were obtained using spirometry. Statistical analyses were used to determine the frequency of mild-moderate (BI > 0) and severe (BI > 12.2) bowing, and to assess the influence of BI on PAS and cough effectiveness in PSP. RESULTS: Fifty-two percent (n = 12) of participants exhibited severe bowing while 48% (n = 11) exhibited mild-to-moderate bowing. Voluntary cough peak expiratory flow rate (P = .01), as well as reflex (P = .02) and voluntary (P = .005) cough volume acceleration were lower for participants with severe BI when compared to mild-to-moderate BI. However, BI did not influence PAS (P > .05). CONCLUSIONS: Findings from this study suggest that vocal fold bowing is highly prevalent in PSP and associated with reduced reflex and voluntary cough effectiveness. These findings provide insight into the pathophysiology of compromised airway protection in this patient population. Future studies should examine vocal fold atrophy as a treatment target for behavioral and medical intervention in PSP. LEVEL OF EVIDENCE: 3 (Prospective Observational Study) Laryngoscope, 131:1217-1222, 2021.

Normative vs. patient-specific brain connectivity in deep brain stimulation.

Brain connectivity profiles seeding from deep brain stimulation (DBS) electrodes have emerged as informative tools to estimate outcome variability across DBS patients. Given the limitations of acquiring and processing patient-specific diffusion-weighted imaging data, a number of studies have employed normative atlases of the human connectome. To date, it remains unclear whether patient-specific connectivity information would strengthen the accuracy of such analyses. Here, we compared similarities and differences between patient-specific, disease-matched and normative structural connectivity data and their ability to predict clinical improvement. Data from 33 patients suffering from Parkinson's Disease who underwent surgery at three different centers were retrospectively collected. Stimulation-dependent connectivity profiles seeding from active contacts were estimated using three modalities, namely patient-specific diffusion-MRI data, age- and disease-matched or normative group connectome data (acquired in healthy young subjects). Based on these profiles, models of optimal connectivity were calculated and used to estimate clinical improvement in out of sample data. All three modalities resulted in highly similar optimal connectivity profiles that could largely reproduce findings from prior research based on this present novel multi-center cohort. In a data-driven approach that estimated optimal whole-brain connectivity profiles, out-of-sample predictions of clinical improvements were calculated. Using either patient-specific connectivity (R = 0.43 at p = 0.001), an age- and disease-matched group connectome (R = 0.25, p = 0.048) and a normative connectome based on healthy/young subjects (R = 0.31 at p = 0.028), significant predictions could be made. Our results of patient-specific connectivity and normative connectomes lead to similar main conclusions about which brain areas are associated with clinical improvement. Still, although results were not significantly different, they hint at the fact that patient-specific connectivity may bear the potential of explaining slightly more variance than group connectomes. Furthermore, use of normative connectomes involves datasets with high signal-to-noise acquired on specialized MRI hardware, while clinical datasets as the ones used here may not exactly match their quality. Our findings support the role of DBS electrode connectivity profiles as a promising method to investigate DBS effects and to potentially guide DBS programming.