Background: Essential tremor (ET) is the most common movement disorder. In cases resistant to pharmacological treatment, functional stereotactic neurosurgery can be an alternative. Lesional surgery has largely been replaced by deep brain stimulation (DBS). The current target of choice is the ventrolateral thalamus (Vim). Vim DBS has generally shown good results, but in some cases it is associated with a suboptimal effect as well as side effects. DBS in the posterior subthalamic area/caudal zona incerta (PSA/cZi) has recently shown promising effects. Recently the role of lesional therapy in selected cases has been discussed. Aim: The aim is to evaluate stereotactic functional procedures in the treatment of ET, with special emphasis on PSA DBS. Further the effects of DBS in the PSA are evaluated. The optimal target is also assessed by evaluating the effect of Vim and PSA DBS in relation to the position of the electrode. An attempt to identify patient-specific factors of prognostic importance for the outcome after DBS will be made. The quality of life (QoL) of patients treated with PSA DBS for ET will be assessed. Finally, the aim is also to analyze retrospectively the long-term outcome of lesional procedures (thalamotomies). Method: The thesis consists of five studies. The optimal electrode location is evaluated in a study analyzing the location of the electrode contact yielding the best effect in Vim DBS and PSA DBS groups. The efficacy of PSA DBS in 21 patients is evaluated in a prospective study. The correlation between outcome, age, tremor grade and gender is established in a prospective study consisting of 68 patients. Finally, the degree of improvement in QoL is determined in 16 patients operated on in the PSA. The very long-term effect of lesional surgery has been investigated in a retrospective study of nine patients who have undergone thalamotomy. Results: In the study of PSA DBS the total score on the Essential Tremor Rating Scale (ETRS) was reduced by 60% compared to the baseline value. Tremor of the arm was improved by 95%. The study evaluating the optimal contact location showed that the best effect was in the PSA in 54% and in the Vim in 12%. The efficacy of DBS was not related to age, gender, or the severity of tremor with regard to the percentage reduction of tremor on stimulation. In patients with a more severe tremor at baseline, a higher degree of residual tremor on stimulation was seen. With regard to QoL, the activities of daily living (ADL) according to the ETRS score were significantly improved, as well as according to the ADL and psychosocial subscores on the Questionnaire for Essential Tremor (QUEST) scale. No significant changes were found on the generic Short Form (SF-36) QoL scale. Thalamotomy had some positive effects, but also a significant amount of side effects that might be attributed to the surgery. Conclusions: The effect of PSA DBS was very satisfying and compares well with the results from Vim DBS. When both Vim and PSA DBS are considered, the optimal target seems to be located in the PSA. PSA DBS shows good results in improving ADL, but the results have been difficult to demonstrate on QoL scales. The efficacy of DBS could not be shown to be associated with gender or age. Nor was it associated with the severity of tremor regarding the percentage of tremor reduction on stimulation. The preoperative severity of tremor was the most important factor regarding outcome following DBS. With regard to thalamotomies, some possible remaining benefit of the surgery could be seen along with some severe side effects.

Στην παρούσα μελέτη παρουσιάσαμε τα αποτελέσματα της λειτουργικής απεικόνισης με SPECT αιμάτωσης εγκεφάλου σε δύο διαφορετικές παθολογικές καταστάσεις, την νόσο του Παρκινσον και τη δευτεροπαθή δυστονία. Στο πρώτο μέρος της μελέτης διερευνήσαμε την ακεραιότητα της μελανοραβδωτής οδού και την αιματική εγκεφαλική ροή στα διάφορα στάδια της νόσου Parkinson. Στη μελέτη συμμετείχαν συνολικά 53 ασθενείς (27 άνδρες, 26 γυναίκες) που πληρούσαν τα κριτήρια της Ιδιοπαθούς νόσου του Parkinson και αξιολογήθηκαν σύμφωνα με την κλίμακα Unified Parkinson Disease Rating Scale (UPDRS) καθώς και την κλίμακα Hoehn-Yahr. Οι ασθενείς χωρίστηκαν σε 4 ομάδες σύμφωνα με την κλίμακα Hoehn-Yahr. Το πρωτόκολλο μελέτης των 53 ασθενών περιελάμβανε 2 απεικονιστικές εξετάσεις: Α) το SPECT εγκεφάλου με το ραδιοφάρμακο 123Ι- Ioflupane (DaTSCAN) και Β) το SPECT αιμάτωσης εγκεφάλου με το ραδιοφάρμακο 99m Tc-ECD (Neurolite ). Η νόσος Πάρκινσον είναι ένα υποκινητικό σύνδρομο και όπως καταδείξαμε από τη μέλετη ασθενών σε διάφορα στάδια της νόσου, το πρότυπο της αιμάτωσης του εγκεφάλου είναι αυτό της σταδιακής προσβολής περιοχών του φλοιού ως συνέπεια της απόσχισης των συνδέσεων του κυκλώματος βασικών γαγγλίων με το φλοιό. Συγκεκριμένα αποδείξαμε ότι στα αρχικά στάδια της νόσου παρατηρείται υποαιμάτωση περιοχών του μετωπιαίου λοβού (κινητικών, προκινητικών και περιοχών του προμετωπαίου λοβού) ενώ σε πιο προχωρημένα στάδια η προσβολή του φλοιού επεκτείνεται σε περιοχές του βρεγματικού και κροταφικού λοβού. Επίσης βρέθηκε θετική συσχέτιση μεταξύ της ειδικής σύνδεσης του ρ/φ στον αριστερό κερκοφόρο πυρήνα και της αιματικής εγκεφαλικής ροής στην περιοχή DLPFC του προμετωπιαίου λοβού αριστερά, καθώς επίσης και μεταξύ της ειδικής σύνδεσης του ρ/φ στο αριστερό κέλυφος και της αιματικής εγκεφαλικής ροής στην πρωτοταγή κινητική περιοχή αριστερά. Στο δεύτερο μέρος της εργασίας μελετήσαμε 21 ασθενείς με Ιδιοπαθή νόσο Parkinson που πληρούσαν τα κριτήρια για χειρουργική αντιμετώπιση με εν τω βάθει εγκεφαλικό ερεθισμό (DBS). Οι ασθενείς ήταν 11 γυναίκες και 10 άνδρες, μέσης ηλικίας 63±8 χρόνια, μέσης διάρκειας της νόσου 11.5±4.8 και σταδίου 2.9±0.8 κατά Hoehn and Yahr. Οι ασθενείς αυτοί υπεβλήθησαν σε 2 ξεχωριστές μελέτες SPECT αιμάτωσης εγκεφάλου, η πρώτη πριν το χειρουργείο (meds off) και η δεύτερη 6 μήνες μετά το χειρουργείο (DBS on/ off meds). Οι δύο αυτές μελέτες συγκρίθηκαν μεταξύ τους με το πρόγραμμα Neurogam και εξετάστηκαν συγκεκριμένα οι μεταβολές στην αιματική εγκεφαλική ροή των κινητικών περιοχών του εγκεφάλου. Παράλληλα εξετάσθηκε η κινητική βελτίωση των ασθενών κλινικά και με βάση την κλίμακα mUPDRS. Τα αποτελέσματα της μελέτης ήταν πολύ καλά καθώς οι 20 ασθενείς παρουσίασαν σημαντική κλινική βελτίωση μειώνοντας την κλίμακα mUPDRS κατά 44% και τη χορηγούμενη δόση levodopa από 850 ± 108 mg πριν το χειρουργείο σε 446 ± 188 mg στο διάστημα επανελέγχου. Επίσης στους 6 μήνες παρατηρήθηκε σημαντική αύξηση της αιματικής εγκεφαλικής ροής στην προκινητική και πρωτοταγή κινητική περιοχή του εγκεφαλικού φλοιού κατά 10.9% και σημαντική συσχέτιση αυτής με την κινητική βελτίωση των ασθενών (r=.89, p<.001). Από τη μελέτη μας προκύπτει ότι το DBS είναι ικανό να άρει την υποαιμάτωση τουλάχιστον των κινητικών περιοχών του φλοιού, οδηγώντας στην κινητική βελτίωση των ασθενών. Στο τρίτο μέρος της μελέτης μας ασχοληθήκαμε με την μελέτη ασθενών με δευτεροπαθή δυστονία που αποτελεί ένα υπερκινητικό σύνδρομο με ετερογένεια όσον αφορά την αιτιολογία του. Συγκεκριμένα μελετήσαμε το αποτέλεσμα της δράσης του DBS στην περιοχική αιματική εγκεφαλική ροή των κινητικών περιοχών του φλοιού σε συνάρτηση με το κλινικό αποτέλεσμα. Στο πρωτόκολλο πριελήφθησαν 6 ασθενείς με φαρμακευτικά ανθεκτική δευτεροπαθή δυστονία που υπεβλήθησαν σε DBS. Οι ασθενείς υπεβλήθησαν σε SPECT αιμάτωσης εγκεφάλου σε δύο διαφορετκές λειτουργικές καταστάσεις μετεγχειρητικά: DBS on & DBS off κατάσταση. Οι δύο μελέτες συγκρίθηκαν μεταξύ τους με το πρόγραμμα Neurogam. Η κινητική εκτίμηση των ασθενών έγινε με την κλίμακα Burke–Fahn–Mardsen Dystonia Rating Scale (BFMDRS) στις δυο διαφορετικές καταστάσεις (DBS on & DBS off). Δύο ασθενείς έδειξαν άριστη κλινική βελτίωση στον επανέλεγχο, σε δύο άλλους τα αποτελέσματα ήταν μέτρια και σε δύο τα αποτελέσματα της επέμβασης κρίθηκαν φτωχά. Ο μέσος βαθμός βελτίωσης της κλίμακας BFMDRS ήταν 49.1% (0–90.7%). Επίσης η ανάλυση των SPECT μελετών έδειξε σημαντική μείωση της rCBF στην κατάσταση on DBS κάτι που συσχετίστηκε με την κλινική βελτίωση. Όσον αφορά το μηχανισμό δράσης του εν τω βάθη εγκεφαλικού ερεθισμού, παρά τις πολλαπλές θεωρίες που υπάρχουν, φαίνεται, τουλάχιστον από το δικό μας μικρό δείγμα ασθενών, να λειτουργεί με το να επαναρυθμίζει το υπάρχων παθολογικό λειτουργικό κύκλωμα σε ένα νέο πιο αρμονικό ρυθμό, προσφέροντας στους ασθενείς μία νέα οδό επικοινωνίας του συστήματος των βασικών γαγγλίων με το φλοιό και στις περισσότερες περιπτώσεις να καταφέρνει να προσφέρει κινητική βελτίωση. / In the present study we present the results of functional brain imaging with regional Cerebral Blood Flow SPECT (rCBF SPECT) in two different neurological disorders; Parkinson’ Disease (PD) and Secondary Dystonia. In the first case of Parkinson’s Disease, our first purpose was to investigate the differences and associations between cortical perfusion and nigrostriatal dopamine pathway in different stages of Parkinson’s disease (PD). For that purpose we recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding). Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Compared with controls, PD patients showed impairments of cerebral perfusion that increased with clinical severity. Furthermore Dopamine transporter binding in the left caudate nucleus and putamen significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC) and primary motor cortex respectively. We concluded that there are significant perfusion deficits, that are associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc). Given the fact that high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an established therapeutic approach for the management of patients with medically intractable idiopathic Parkinson’s disease (PD), our second purpose was to to assess regional cerebral blood flow (rCBF) changes related to motor improvement after Deep Brain Stimulation of the Subthalamic Nucleus (STN DBS). For that purpose we studied twenty-one PD patients (11 females and 10 males, mean age 63±8, mean disease duration 11.5±4.8, mean Hoehn and Yahr stage:2.9±0.8), that underwent two rCBF SPECT studies at rest, once preoperatively in the off-meds state and the other postoperatively (at 6±2 months) in the off-meds/on-stimulation state. Patients were classified according to the Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. Neurogam software was used to register, quantify and compare two sequential brain SPECT studies of the same patient in order to investigate rCBF changes during STN stimulation in comparison with preoperative rCBF. The results showed that all patients presented clinical improvement during the first months after surgery resulting in a 44% reduction of the UPDRS motor score. The administered mean daily levodopa dose significantly decreased from 850 ± 108 mg before surgery to 446 ± 188 mg during off meds state (p < .001, paired t-test). At the 6 month postoperative assessment we noticed rCBF increases in the pre-supplementary motor area (pre-SMA) and the premotor cortex (PMC) (mean rCBF increase=10.9%), the dorsolateral prefrontal cortex and in associative and limbic territories of the frontal cortex (mean rCBF increase=8.2%). A correlation was detected between the improvement in motor scores and the rCBF increase in the pre-SMA and PMC (r=.89, p<.001). Our study suggests that STN stimulation leads to improvement in neural activity in the frontal motor/associative areas. The correlation between motor improvement and rCBF increase in higher order motor cortical areas suggests that even the short term stimulation achieves its therapeutic benefit by restoring the activity within these cortical regions. In the third part of our study we investigated the effect of deep brain stimulation (DBS) on regional cerebral blood flow (rCBF) in cases of secondary dystonia in correlation with clinical outcomes. For that purpose we studied six patients with medically intractable secondary dystonia who underwent DBS surgery. Burke–Fahn–Mardsen Dystonia Rating Scale (BFMDRS) was used for the assessment of dystonia, in the on & off DBS state. Single photon emission computed tomography (SPECT) of the brain was performed postoperatively in the two stimulation states (ON-DBS and OFFDBS) and the changes of rCBF in the three following brain regions of interest (ROIs): primary motor cortex, premotor and supplementary motor cortex, and prefrontal cortex were evaluated. Two patients exhibited excellent response to DBS, two patients got moderate benefit after the procedure, and in two patients, no clinical improvement was achieved. A mean improvement of 49.1% (0–90.7%) in BFMDRS total scores was found postoperatively. Brain SPECT data analysis revealed an overall decrease in rCBF in the investigated ROIs, during the ON-DBS state. Clinical improvement was significantly correlated with the observed decrease in rCBF in the presence of DBS. We concluded that when conservative treatment fails to relieve severely disabled patients suffering from secondary dystonia, DBS may be a promising therapeutic alternative. Moreover, thiat study indicates a putative role of brain SPECT imaging as a postoperative indicator of clinical responsiveness to DBS.

Introdução: A estimulação cerebral profunda (DBS) tem sido utilizada para controle das alterações motoras nos pacientes com Doença de Parkinson (DP). O núcleo subtalâmico (NST) é o alvo preferencialmente escolhido na cirurgia. Entretanto, a técnica tem sido associada com declínio cognitivo, principalmente na fluência verbal, alterações de humor e de comportamento. Objetivo: Verificar a ocorrência de alterações na cognição, humor e atividades funcionais por meio de avaliação neuropsicológica. Métodos: Vinte e um pacientes submetidos à cirurgia no período de Maio de 2008 a Março de 2013 foram examinados por meio da avaliação neuropsicológica incluindo testes de memória, funções executivas, funções atencionais, linguagem, praxia, escala hospitalar de depressão e ansiedade (HADS) e atividades funcionais (Pfeffer), nas fases pré e pós-operatória. Os dados foram analisados utilizando SPSS versão 17.0 e os resultados foram comparados através do teste pareado t-Student ou chi-quadrado. Foi adotado um nível de significância igual ou menor que 5% (p < 0,05) para todas as análises. Resultados: Não foram encontradas diferenças significativas nas funções cognitivas, no humor e nas atividades funcionais avaliadas. Resultado marginal foi observado na memória episódica imediata verbal (p=0,051). Conclusão: DBS-NST parece não ter impacto negativo nas funções cognitivas e humor. Apesar da amostra ser relativamente pequena, a técnica parece ser segura do ponto de visto cognitivo em pacientes adequadamente selecionados / Introdution: Deep brain stimulation (DBS) has been used for control of motor disorders in patients with Parkinson\'s disease (PD). The subthalamic nucleus (STN) is the main target used in surgery. However, the technique has been associated with cognitive decline, mainly in verbal fluency, mood and behavior. Objective: To investigate the occurrence of changes in cognition, mood, and activities of daily living through neuropsychological assessment. Methods: Twenty one patients operated between May, 2008 and March, 2013 were submitted to pre- and post-operative neuropsychological testing including memory, executive functions, attentional functions, language and praxis assessment, and to hospital anxiety and depression scale (HADS) and activities of daily living (Pfeffer) scale rating as well. Data were analyzed using SPSS version 17.0 and the results were compared using the paired Student t-test or chi-square. A significance level equal or lower than 5% (p < 0.05) was adopted. Results: No significant differences were found in cognitive functions, mood and activities of daily living. Marginal results were observed in immediate verbal episodic memory (p=0.051). Conclusion: DBS - STN did not show a negative impact on cognitive function, mood and daily activities. Despite the relatively small sample, the technique appears to be safe from the cognitive point of view in appropriately selected patients

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been gaining importance in the treatment of advanced Parkinson's disease. This study was undertaken to evaluate the beneficial effects of bilateral STN stimulation on patient's clinical symptoms and quality of life related to the potential risks and side effects of the treatment. A consecutive series of 42 patients operated on for Parkinson's disease with STN DBS in Oulu University Hospital were included. A subgroup of these patients was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), neuropsychological tests, and Health Related Quality of Life (HRQoL) instruments i.e. the Parkinson's Disease Questionnaire (PDQ-39) and the Finnish version of the Nottingham Health Profile (NHP). The costs of the treatment were calculated from the perspective of the health care provider. The possible effects of bilateral STN-operation on cardiovascular autonomic function were analyzed by measuring various time- and frequency domain indexes as well as non-linear indexes of heart rate variability (HRV) from 24-hour EKG recording before and 12 months after the operation. This study showed that STN DBS significantly improves the clinical symptoms and HRQoL of parkinsonian patients. The dyskinesia and clinical fluctuation scores were reduced very significantly in the UPDRS IV subscale. The clinical fluctuations were reduced by 53 %. After DBS best motor response (UPDRS III) scores also improved significantly. The HRQoL measured with both instruments improved significantly. Improvement was seen in the PDQ-39 summary index and the subscales of activities of daily living, emotional well-being, stigma and bodily discomfort. Only communication became worse during the follow-up. There was a statistically significant improvement in the score of the subscales of NHP measuring problems with energy, sleep, emotional reactions and social isolation. One patient died from pulmonary embolism and another contracted a late postoperative intracerebral hemorrhage leading to a permanent deterioration of her neurological condition to the bedridden stage. Other complications were much milder. Clinical improvement and improvement in HRQoL were positively correlated. STN DBS does not influence tonic autonomic cardiovascular regulation. The incremental costs of performing bilateral STN DBS in Finland compared to preoperative medical treatment amounted to an average of 25 591 EUR per patient during the first postoperative year. The majority of parkinsonian patients experienced significant and long lasting relief in their motor symptoms and an improvement in HRQoL following STN stimulation.

Breathing is an automatic process that we hardly pay any attention to in our daily life. As a social species, we interact using body movement, speech and emotion and these actions require modification of the respiratory pattern. While we understood how the respiratory rhythm is generated, we do not have clear evidence on how higher cortical signals modulate the respiratory pattern. The deep cortical structures in the human brain are inaccessible under normal circumstances, and deep brain stimulation electrode recordings offer an opportunity to understand the neurophysiological interactions ofdeeper brain structures. In this thesis, I investigated deep brain stimulation recordings from implanted electrodes in chronic neuropathic pain subjects in the right and left anterior cingulate cortices, the ventral posterior lateral nucleus of the thalamus and periventricular gray region. The objectives of this research were to elucidate the feed-forward mechanisms of volitional breathing, cortical autonomic regulation, and to investigate whether any of the investigated nuclei haveany carbon dioxide-sensitive neurons which may encode respiratory sensation. The results show lateralisation of the cortical autonomic control whereby the left anterior cingulate exhibits increases in beta band activity (30 to 90 Hz) with cognition and vocalisation tasks. Meanwhile, right anterior cingulate activity increases with hyperoxia. Respiration using various carbon dioxide concentrations shows a constant rise in the alpha band (8 to 14 Hz) activity in the PVG which suggests a sensitive, nonspecific neuronal activity related to systemic carbon dioxide levels.

Les Troubles Obsessionnels Compulsifs (TOC) sont composés de compulsions, qui sont des comportements répétés, et d'obsessions, qui sont des pensées intrusives. Leurs impacts sur le fonctionnement socio-professionnel handicapent et isolent considérablement les patients. Les traitements efficaces pour ces patients sont médicamenteux ou les thérapies cognitives et comportementales. Néanmoins, un nombre élevé de patients ne voient pas leurs symptômes diminuer suffisamment avec l'un ou l'autre des traitements ou en les combinant. Il est donc nécessaire de développer des traitements intermédiaires afin d'améliorer la palette de traitements des TOC. Une alternative thérapeutique utilisée en psychiatrie pour la dépression est la Stimulation Magnétique Transcrânienne répétée (TMS). Néanmoins, son efficacité reste difficile à démontrer dans le TOC, dû à une multitude de facteurs à prendre en compte, et peut nécessiter d'étudier le fonctionnement de la rTMS sur une population de sujets sains. Lors de notre première étude, nous avons évalué l'impact d'un protocole de rTMS sur les fonctions cognitives de sujets sains. Nous avons donc pu observer, indépendamment de la pathologie, l'effet de deux semaines de TMS sur les performances cognitives et sur l'activité cérébrale. Malgré une absence d'effet comportemental, une modification du réseau cortico-sous-cortical lié à une tâche de mémoire de travail a pu être montrée. Ces résultats orientent les recherches futures à modifier l'approche méthodologique, améliorer l'approche clinique des TOC, et changer l'approche neurophysiologique de la TMS dans le but de proposer un traitement complémentaire pour améliorer l'état clinique des patients. / Obsessive Compulsive Disorder (OCD) is a mental illness defined by the presence of compulsions which are repetitive behaviors and obsessions which are intrusive thoughts. OCD may have a dramatic impact on the social and professional lifes of patients. The treatments for OCD are medication and cognitive-behavioral therapy. Nevertheless, symptoms remain in 25 to 40% of patients. Repeated Transcranial Magnetic Stimulation (rTMS) represent a novel therapeutic option for OCD patients however its effectiveness has been difficult to prove partly due to a multitude of factors involving the rTMS technique itself. The first study evaluated the impact of a two-week rTMS protocol on cognitive functions in healthy subjects using fMRI during a working-memory task. In the absence of behavioral modification, we observed that compared to sham, rTMS induced changes at multiple nodes of the cerebral network activated by the task beyond the stimulation site. This result represents an encouraging perspective for rTMS intervention on pathological brain network in OCD because hyperactive regions in this disorder (orbitofrontal cortex and anterior cingulate cortex) are too deep to be directly stimulated by rTMS. Our second study targeted the supplementary motor area (SMA), which had been suggested as candidate target region lying near the anterior cingulate cortex. We used for four week rTMS in a group of OCD patients while pre- and post-treatment fMRI was acquired during performance of a cognitive inhibition task. Stimulation of the SMA did not result in significant clinical improvement. These results shall guide future research to address the methodological challenges and the neurophysiological mechanisms of rTMS to improve its clinical efficacy for OCD.

Machine collaboration with the biological body/brain by sending electrical information back and forth is one of the leading research areas in neuro-engineering during the twenty-first century. Hence, Brain-Machine-Brain Interface (BMBI) is a powerful tool for achieving such machine-brain/body collaboration. BMBI generally is a smart device (usually invasive) that can record, store, and analyze neural activities, and generate corresponding responses in the form of electrical pulses to stimulate specific brain regions. The Smart Brain-Machine-Brain-Interface (SBMBI) is a step forward with compared to the traditional BMBI by including smart functions, such as in-electrode local computing capabilities, and availability of cloud connectivity in the system to take the advantage of powerful cloud computation in decision making. In this dissertation work, we designed and developed an innovative form of Smart Brain-Machine-Brain Interface (SBMBI) and studied its feasibility in different biomedical applications. With respect to power management, the SBMBI is a semi-passive platform. The communication module is fully passive—powered by RF harvested energy; whereas, the signal processing core is battery-assisted. The efficiency of the implemented RF energy harvester was measured to be 0.005%. One of potential applications of SBMBI is to configure a Smart Deep-Brain-Stimulator (SDBS) based on the general SBMBI platform. The SDBS consists of brain-implantable smart electrodes and a wireless-connected external controller. The SDBS electrodes operate as completely autonomous electronic implants that are capable of sensing and recording neural activities in real time, performing local processing, and generating arbitrary waveforms for neuro-stimulation. A bidirectional, secure, fully-passive wireless communication backbone was designed and integrated into this smart electrode to maintain contact between the smart electrodes and the controller. The standard EPC-Global protocol has been modified and adopted as the communication protocol in this design. The proposed SDBS, by using a SBMBI platform, was demonstrated and tested through a hardware prototype. Additionally the SBMBI was employed to develop a low-power wireless ECG data acquisition device. This device captures cardiac pulses through a non-invasive magnetic resonance electrode, processes the signal and sends it to the backend computer through the SBMBI interface. Analysis was performed to verify the integrity of received ECG data.

No description available.

No description available.

Deep brain stimulation (DBS) is a neurosurgical intervention now established for the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, several prospective case series have been reported, but few centres worldwide have published findings from patients treated during the last decade using current standards of technology. This thesis seeks to survey the current clinical status of DBS for pain, investigate its mechanisms and their interactions with autonomic function, its clinical limitations and ablative alternatives. Presented first is a review of the current status of analgesic DBS including contemporary clinical studies. The historical background, scientific rationale, patient selection and assessment methods, surgical techniques and results are described. The clinical outcomes of DBS of the sensory thalamus and periventricular / periaqueductal grey (PAVG) matter in two centres are presented including results from several pain and quality of life measures. A series of translational investigations in human subjects receiving DBS for pain elucidating mechanisms of analgesic DBS and its effects upon autonomic function are then presented. Single photon emission tomography comparing PAVG, VP thalamus and dual target stimulation is described. Somatosensory and local field potential (LFP) recordings suggesting PAVG somatotopy are shown. ABPM results demonstrating changes with PAVG DBS are given and Portapres studies into heart rate variability changes with ventral PAVG DBS are detailed. Investigations using naloxone are then shown to hypothesise separate dorsal opioidergic and ventral parasympathetic analgesic streams in the PAVG. Finally, cingulotomy in lung cancer to relieve pain and dyspnoea results are discussed in the context of altering pain and autonomic function by functional neurosurgery. Pain and autonomic interactions and mechanisms in deep brain surgery for pain are then discussed alongside its limitations with proposals made for optimising treatment and improving outcomes.