No description available.

No description available.

Background: Patients with Parkinson’s disease (PD) and Essential tremor (ET) who havebeen treated with Deep Brain Stimulation (DBS) generally experience a positive effect,particularly regarding the motor symptoms. However, the patients’ communication skillsare often negatively affected and the assessment instrument currently used withinneurological clinical care is not sufficiently sensitive to assess these patients’ speechclarity, voice and intelligibility satisfactorily.Aim: This study’s purpose was to develop a prototype assessment tool for speech clarity,intelligibility and voice, with speech and language pathology (SLP) validity, that isadaptable to a neurological clinical care setting.Method: The assessment tool was designed using general design methodology. Aprototype was constructed and tested on speech samples of read text for reliability. ThreeSLP’s, three DBS nurses and three naive listeners (NL) were represented in the test group.Levels of agreement were calculated using Percent Close Agreement, PCA.Results: The results indicate a relatively high level of agreement between the groups, inparticular the SLP group and the DBS group (μ: 0.82, 0.79, and 0.74).Conclusion: The results demonstrate the need for an assessment tool with SLPcompetence to assess speech clarity, intelligibility and voice within neurological clinicalcare. The assessment tool was shown to be a useful and adequate prototype that can easilyevolve into a truly useful and versatile perceptual speech assessment tool. The results ofthis study should be treated cautiously, considering the test groups’ modest size. / Bakgrund: Patienter med Parkinsons sjukdom (PD) och patienter med Essentiell tremor(ET) som behandlats med Deep Brain Stimulation (DBS) upplever i allmänhet en positiveffekt, framför allt gällande de motoriska symtomen. Emellertid påverkas oftapatienternas kommunikativa färdigheter negativt. De bedömingsmaterial som användsinom den kliniska nerurologiska vården; UPDRS/ETRS är alltför trubbiga för att kunna geen tillfredsställande bild av patientens tal, röst och förståelighet.Mål: Skapa ett bedömningsverktyg för tal, förståelighet och röst med logopedisk validitet,och som kan användas inom den kliniska neurologiska verksamheten i samband medDBS-behandling.Metod: Bedömningsverktyget designades enligt generell designmetodik. En prototypskapades och testades för reliabilitet på röstexempel av en läst text. Tre logopeder, treDBS-sköterskor och tre naiva lyssnare deltog i testningen. Grad av samstämmighetberäknades med Percent Close Agreement, PCA.Resultat: Resultaten indikerar en relativt hög grad av samstämmighet mellan grupperna(μ: 0.82, 0.79, respektive 0.74). Logopederna bedömde nästan alla röstexempel sompatienter i behov av logopedhjälp. DBS-gruppen och gruppen med naiva lyssnarebedömde ett mindre antal ha behov av logoped.Slutsats: Resultaten belyser behovet av ett bedömningsverktyg med logopedisk validitetför bedöming av tal, förståelighet och röst inom den kliniska neurologiska verksamheten.Bedömingsverktyget som framtagits i denna studie är en användbar och adekvat prototypsom enkelt skulle kunna utvecklas till ett verkligt användbart och mångsidigt perceptuelltbedömningsmaterial. Dock ska resultaten i denna studie tolkas en smula försiktigt medtanke på de låga antalet deltagare.

Our understanding of the pathophysiology Parkinson’s disease has transformed over the last decade as we have come to appreciate the importance of changes in neuronal firing pattern that occur within the motor network in the dopamine deficient state. These changes in firing pattern, particularly increased synchrony result in oscillations that can be recorded as local field potentials. This thesis concerns itself with the study of beta oscillations which are characteristic of Parkinson’s disease. Firstly, I investigate whether beta oscillations play a pathophysiological role in Parkinson’s disease or whether they are purely epiphenomenal by augmenting beta with low frequency deep brain stimulation. In this study I show that rigidity is increased by ~25% with low frequency stimulation providing significant further evidence for a patho-physiological role of beta in Parkinson’s disease. Next I investigate whether beta oscillations correlate with Parkinsonian severity at rest and could therefore potentially be used as a biomarker of clinical state. I demonstrate that the variability of beta amplitude recorded from the subthalamic nucleus strongly correlates with symptom severity at rest and also in response to levodopa administration. I then use beta amplitude as a biomarker for a trial of adaptive deep brain stimulation in Parkinson’s disease. I show that by using beta amplitude to control stimulation, time on stimulation is reduced by >50% but despite this, clinical outcome is improved by 25% relative to conventional continuous high frequency stimulation. Finally, I investigate the bilateral subcortical beta network and its response to levodopa. I report statistically significant bilateral functional connectivity in the beta range which is driven by phase locking and modulated by levodopa in the low beta range with implications for bilateral adaptive deep brain stimulation. These findings further our understanding of the pathophysiological role of beta oscillations in Parkinson’s disease and provide new avenues for treatment development.

Relatively little is known about the role of the basal ganglia and their pathways in human deglutition. Deep Brain Stimulation (DBS) is a treatment for Parkinson Disease (PD) that stimulates the subthalamic nuclei and affords us a model for examining deglutition in humans with known impairment of the basal ganglia. The purpose of this study was to examine the effects of DBS in the ON versus Off conditions on the oral and pharyngeal stages of deglutition in participants with PD. It was hypothesized that DBS in the ON condition would yield improvement in the following dependent variables: oral total composite score, pharyngeal total composite score, pharyngeal transit time, and maximal hyoid bone excursion. Statistically significant differences (improvement) were found for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition. Findings of this study demonstrated that DBS in the ON condition helps to alleviate some of the bradykinesia and hypokinesia associated with PD on the pharyngeal stage of deglutition, but not the oral stage. These findings suggest that Parkinsonian swallowing dysfunction is not solely related to nigrostriatal dopamine deficiency which is purported to be the primary means of DBS alleviation of motor signs. Rather, it may be due to an additional non-dopamine related system of deglutition found in the brainstem.

Background The last decade has witnessed a renaissance of functional stereotactic neurosurgery in the treatment of patients with movement disorders, especially advanced Parkinson’s disease (PD), essential tremor (ET) and dystonia. Ablative lesions such as thalamotomy and pallidotomy have been gradually replaced by the technique of chronic deep brain stimulation (DBS) applied to targets in the basal ganglia and thalamus, and assumed to be more lenient to the brain than stereotactic radiofrequency lesions. Since the aim of functional neurosurgery is to alleviate symptoms of these chronic, progressive, non-fatal diseases, and to improve life quality of the patients, it is imperative that the surgical procedures remain safe and do not result in complications mitigating any anticipated positive effect of the surgery on the symptoms of the disease. Aim The aim of this thesis is to evaluate, compare and analyse the safety of various surgical procedures used to treat patients with movement disorders, and to document side effects and complications both peri operatively and in a long term follow-up. Further to compare the effects of pallidotomy and pallidal DBS, and to evaluate the longterm efficacy of Vim-DBS. Method 256 consecutive surgical procedures, 129 DBS and 127 stereotactic lesions, were reviewed with respect to complications in 197 treated patients. In a series of 119 patients operated on with DBS during a 10 year period, the occurrence of hardware related complications (infection, breakage, erosion etc) was documented and analysed. Additionally, the interference of external magnetic field with the stimulation was documented. In one patient operated on with subthalamic nucleus DBS, a highly unusual and unexpected psychiatric side effect was carefully analysed. In 5 patients operated on with both methods (lesion and DBS) on each hemisphere, respectively, the effect and side effects of each method were compared. The long term effect and side effects of thalamic DBS was analysed in a series of patients with ET followed for 7 years. Results There were no deaths and few severe neurological complications in this material. Unilateral ablative lesions in the pallidum were well tolerated by patients with advanced PD, while for tremor, thalamic DBS was much safer than thalamotomy, even if its effect on certain aspects of tremor could show some decrease of efficacy over time. Some of the side effects of lesioning are transient while most but not all side effects of DBS are reversible. Hardware-related complications were not uncommon especially in the early “learning curve” period, and the DBS technique, being a life-long therapy, will necessitate a life long follow up of patients. Provided safety protocols are followed and provided patient’s and carer’s education and awareness, external electromagnetic interference should not constitute a risk for patients with DBS. PD patients undergoing STN DBS should be carefully selected to avoid psychiatric or cognitive side effects, due to this brain target´s proximity to, and involvment in, non-motor associative and limbic circuitry. Conclusions In terms of mortality and morbidity, modern stereotactic neurosurgery for movement disorders, both ablation and DBS, is a safe procedure even in advanced stages of disease. Symptoms of PD, ET and dystonia can be alleviated mainly with DBS and even unilaterally with pallidal lesions, at the expense of, in most cases, minor side-effects.

Parkinson’s disease (PD) and dystonia are movement disorders related to dysfunctions of basal ganglia (BG). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) are treatments for PD and dystonia. Previous research indicated that abnormally elevated oscillatory activities at the theta (3-10 Hz) beta frequency bands (11-30 Hz) may be related to parkinsonian and dystonic motor symptoms but their precise roles are not well understood. Recently, DBS of the pedunculopontine nucleus region (PPNR) has been used to treat PD patients with postural and gait dysfunctions, but movement-related PPNR activities had not been explored. We aimed to investigate movement-related local field potentials (LFP) recorded from the BG and PPNR in PD and dystonia patients. We recorded STN LFP from PD patients and subsequently applied the intrinsic STN theta, beta, and gamma (31-100 Hz) frequencies through DBS to study their effects on PD motor signs. We also recorded movement-related PPNR LFP in PD patients and movement-related GPi activities in patients with primary dystonia. Finally, we simultaneously recorded movement-related activities from the GPi and the motor thalamus in a patient with secondary dystonia. We found that DBS at the dopamine-dependent and movement-related intrinsic STN gamma frequencies, were as effective as traditionally used high frequencies (130-185 Hz) in reducing PD motor signs, but theta and beta frequencies did not worsen motor symptoms. Voluntary movements modulated two discrete movement-related frequencies in the theta and beta bands in the PPNR and these two frequencies interacted with the sensorimotor and frontal cortices during movements. We showed that voluntary movements modulated beta and gamma frequencies in the GPi. A resting ~5-18 Hz coherence between the GPi bilaterally was attenuated during movements in patients, which may be related to dystonia because this 5-18Hz coherence was also present between the GPi and motor thalamus in the patient with secondary dystonia. Our findings indicated that intrinsic STN gamma frequency oscillations were likely prokinetic rhythms but theta and beta frequencies may not contribute to PD motor symptoms. Voluntary movements modulated theta and beta frequencies in the PPNR, which may explain why PPNR DBS uses lower frequencies than those of the BG. The 5-18 Hz oscillatory activities in the BG-thalamic circuit may be a feature of dystonia.

Parkinson’s disease (PD) and dystonia are movement disorders related to dysfunctions of basal ganglia (BG). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) are treatments for PD and dystonia. Previous research indicated that abnormally elevated oscillatory activities at the theta (3-10 Hz) beta frequency bands (11-30 Hz) may be related to parkinsonian and dystonic motor symptoms but their precise roles are not well understood. Recently, DBS of the pedunculopontine nucleus region (PPNR) has been used to treat PD patients with postural and gait dysfunctions, but movement-related PPNR activities had not been explored. We aimed to investigate movement-related local field potentials (LFP) recorded from the BG and PPNR in PD and dystonia patients. We recorded STN LFP from PD patients and subsequently applied the intrinsic STN theta, beta, and gamma (31-100 Hz) frequencies through DBS to study their effects on PD motor signs. We also recorded movement-related PPNR LFP in PD patients and movement-related GPi activities in patients with primary dystonia. Finally, we simultaneously recorded movement-related activities from the GPi and the motor thalamus in a patient with secondary dystonia. We found that DBS at the dopamine-dependent and movement-related intrinsic STN gamma frequencies, were as effective as traditionally used high frequencies (130-185 Hz) in reducing PD motor signs, but theta and beta frequencies did not worsen motor symptoms. Voluntary movements modulated two discrete movement-related frequencies in the theta and beta bands in the PPNR and these two frequencies interacted with the sensorimotor and frontal cortices during movements. We showed that voluntary movements modulated beta and gamma frequencies in the GPi. A resting ~5-18 Hz coherence between the GPi bilaterally was attenuated during movements in patients, which may be related to dystonia because this 5-18Hz coherence was also present between the GPi and motor thalamus in the patient with secondary dystonia. Our findings indicated that intrinsic STN gamma frequency oscillations were likely prokinetic rhythms but theta and beta frequencies may not contribute to PD motor symptoms. Voluntary movements modulated theta and beta frequencies in the PPNR, which may explain why PPNR DBS uses lower frequencies than those of the BG. The 5-18 Hz oscillatory activities in the BG-thalamic circuit may be a feature of dystonia.

<p>Deep brain stimulation (DBS) is an established treatment for movement disorders that has been implanted in more than 40,000 patients worldwide. Despite the successes of DBS, its mechanisms of action are not well understood. Early descriptions of the mechanisms of DBS focused on whether DBS excited or inhibited neurons in the stimulated nucleus. However, changes in the <italic>patterns</italic> of neuronal activity, and not just changes in the rate of neuronal activity, play a major role in the pathology of movement disorders. Therefore, we hypothesized that the temporal pattern of stimulation might be an important factor in determining the effectiveness of DBS. The purpose of this dissertation was to use temporally <italic>irregular</italic> patterns of stimulation (non-regular interpulse intervals) to probe the mechanisms of thalamic DBS in suppressing tremor. The clinical tremor measurements reported in this dissertation represent the first tremor data published during stimulation with temporally <italic>irregular</italic> stimulus trains in human subjects. First, we tested the effects of paired-pulse DBS on tremor suppression in human subjects with essential tremor and on the responses of a computational model of thalamic neurons. DBS was more effective at reducing tremor when pulses were evenly spaced than when there were large differences between intrapair and interpair pulse intervals, suggesting that tremor suppression is dependent on the <italic>pattern</italic> of DBS and not just the average rate of stimulation. Increasing the difference between the intrapair and interpair intervals in the computational model rendered model neurons more likely to fire synchronous bursts. Second, we quantified the effects of the degree of regularity of temporally random stimulus trains in human subjects with tremor. We pioneered an innovative preparation to conduct these experiments--during surgery to replace the implantable pulse generator--which allowed us to establish a direct connection to implanted DBS leads under stable conditions. Stimulus trains were less effective at relieving tremor as the temporal spacing between stimulus pulses in DBS trains became more irregular. However, the reasons for the decreased efficacy of the temporally irregular stimulus trains was not clear. Third, we evaluated the contributions of `<italic>pauses</italic>,' `<italic>bursts</italic>,' and `<italic>irregularity, per se</italic>' to the inability of irregular stimulus trains to suppress tremor. Stimulus trains with <italic>pauses</italic> were significantly less effective at suppressing tremor than stimulus trains without <italic>pauses</italic>, while there were no significant changes in tremor suppression between trains with <italic>bursts</italic> and those without <italic>bursts</italic>, or between trains that were <italic>irregular</italic> and those that were <italic>periodic</italic>. We also developed a computer-based biophysical model of a thalamic network to simulate the response of thalamic neurons to the same temporal patterns of DBS. Trains that effectively suppressed tremor in human subjects also suppressed fluctuations in transmembrane potential at the frequency associated with burst-driven cerebellar inputs to the thalamus. Both clinical and computational findings indicate that DBS suppresses tremor by masking cerebellar burst-driven input to the thalamus.</p><p>The work in this dissertation bridges an important gap between the hypothesis that high-frequency DBS masks pathological activity in the cerebello-thalamo-cortical circuit and the experimentally observed finding that DBS in the subthalamic area suppresses tremor more effectively than DBS in the Vim thalamus proper. We provided experimental and computational evidence that the mechanism of DBS is to mask the burst-driven cerebellar inputs to the thalamus. Hence, the most relevant neuronal targets for effective tremor suppression are the afferent cerebellar fibers that terminate in the thalamus.</p> / Dissertation

This report will review critically the available research on deep brain stimulation and levodopa as a means of treatment for Parkinson’s disease in an attempt to determine why neither of these treatments improves speech. / text