The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of midbrain and pons. The PPN in animal models appears topographically organised and functionally related to locomotion and arousal. In Parkinson’s disease, the PPN degenerates and is susceptible to abnormal basal ganglia output. In patients with Parkinson’s disease, low frequency PPN stimulation is proposed to improve gait freezing and postural instability. However, the therapeutic mechanisms, optimal clinical application and precise effects on gait and posture of PPN stimulation are unclear. Here, a topographic arrangement of the PPN was supported by local field potential recordings in parkinsonian patients. In the PPN region, beta oscillations were recorded rostrally and alpha oscillations caudally. Alpha oscillations, consistent with their putative role in allocating attention, correlated with gait performance and attenuated with gait freezing. Thus the caudal PPN subregion may be the most relevant target for gait disorders. Accordingly, an unblinded clinical study suggested that stimulation of the caudal PPN subregion was beneficial for gait freezing, postural instability and falls. In a double-blinded study using spatiotemporal gait analysis, caudal PPN stimulation reduced triggered gait freezing, with bilateral stimulation more effective than unilateral. However, akinesia including akinetic gait did not improve with PPN stimulation. Accordingly, dopaminergic medication requirements did not change. Mechanisms underlying gait freezing and PPN stimulation were explored with reaction time experiments. Parkinsonian patients with severe gait freezing and postural instability demonstrated a ‘block’ to pre-programmed movement. This was evidenced by prolonged simple reaction times and the absence of ‘StartReact’, whereby pre-prepared responses are normally accelerated by loud acoustic stimuli. PPN stimulation improved simple reaction time and restored Startreact. The relief of this ‘motor block’ with PPN stimulation may therefore explain the associated improvement in gait freezing and postural instability, as these tend to occur in circumstances requiring triggered, pre-prepared adjustments.

Parkinson's disease (PD) is characterized by debilitating impairments in motor control arising from pathophysiological alterations in basal ganglia circuitry and function. In this research thesis two main approaches, namely electrical recording and stimulation, are combined in order to better understand motor performance in Parkinson's disease and ways it might be improved. Three main types of motor behaviors are studied: discrete ballistic movement, repetitive movement, and motor adaptation. <ul><li>First, deep brain stimulation (DBS) of the subthalamic nucleus (STN) was shown to improve the velocity of discrete, ballistic movements in PD. The neural correlates of ballistic movements were then studied by recording from the STN of PD patients, revealing onset of beta-range desynchronization prior to, and gamma-range frequency synchronization during, performance of fast arm reaches. To determine a causal role for these oscillatory frequencies in motor behavior, the motor cortex of healthy humans was stimulated at either beta or gamma frequency during a 'go/no-go' grip force task. Beta stimulation resulted in slower force generation on 'go' trials but enhanced inhibition during 'no-go' trials, whereas gamma stimulation resulted in faster force generation on 'go' trials.</li> <li>Second, STN DBS resulted in improved repetitive tapping performance in PD patients through a reduction in variability. Recordings from the STN demonstrated that repetitive movement was accompanied by a substantial and persistent suppression of beta oscillatory activity.</li> <li>Third, Parkinson's patients were tested on a motor adaptation task, revealing intact learning but impaired retention of a visuomotor rotation. Application of direct current stimulation of the motor cortex resulted in enhanced adaptation during both learning and retention in PD patients and healthy controls.</li> <li>These results causally implicate the basal ganglia and oscillatory activity in motor control, provide insight into the neuronal mechanisms of motor performance and adaptation, and demonstrate promising new avenues for enhancing motor control in Parkinson's disease.</li></ul>

The subthalamic nucleus (STN), which is the most common target for deep brain stimulation for Parkinson's disease, is known to be crucially involved in motor control. Recent appreciation of the potential non-motor side effects of STN deep brain stimulation, however, has led to speculation that the importance of this nucleus may also relate to processes involved in decision- making, particularly during high conflict scenarios. This thesis concerns itself with investigating the STN's role in action selection during conflict. I begin by recording local field potentials directly from the STN of Parkinson's disease patients while they perform a flanker task that has been shown to elicit theta (4-8 Hz) band activity in areas of the prefrontal cortex involved in cognitive control. I report that like the prefrontal cortex, the STN demonstrates elevated theta activity during conflict. I then test whether STN theta activity is related to that of the prefrontal cortex by recording from both sites simultaneously while patients perform a novel task that temporally separates conflict from stimulus onset or movement. This reveals that theta activity indeed becomes synchronized during conflict, with cortical oscillations driving those of the STN. Thirdly, I investigate how STN oscillations may affect firing rate dynamics by intra-operatively recording local field potentials and single unit activity from patients performing the flanker task. I report that both theta and beta (15-30 Hz) oscillations entrain STN neurons, but only during conflict. Finally, I record cortical and STN activity while a fourth group of patients performs the flanker task. This experiment confirms that cortico-STN theta synchrony is elevated during conflict and may also relate to across-trial adaptations to conflict and errors. Taken together these studies shed light on the mechanisms by which cortical structures may influence the STN during conflict and why STN deep brain stimulation may result in impulsivity.

avitsir@ccf.org / Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson’s disease (PD) patients undergoing DBS procedure between 2008–2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson’s Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00–1.02; p = 0.005), high Joint National Committee (JNC) class (p < 0.0001), diabetes mellitus (RR 1.4; 95%CI 1.2–17; p < 0.0001) and duration of PD >10 years (RR 1.2; 95%CI 1.1–1.3; p = 0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p = 0.1) and levodopa equivalent dose (p = 0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p = 0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications. / Revisión por pares

Submitted by Carvalho Dias João Paulo (joao.dias@famerp.br) on 2018-04-12T17:42:05Z No. of bitstreams: 1 karinakellyborges_tese.pdf: 4166303 bytes, checksum: 6285f0b896e90ee79617143e2fd72af2 (MD5) / Made available in DSpace on 2018-04-12T17:42:05Z (GMT). No. of bitstreams: 1 karinakellyborges_tese.pdf: 4166303 bytes, checksum: 6285f0b896e90ee79617143e2fd72af2 (MD5) Previous issue date: 2016-11-24 / Introduction: Parkinson's disease (PD) is a chronic progressive disease that affects physical, cognitive and emotional aspects. Objective: The aim of this study was to evaluate the occurrence of changes in cognition and symptoms of mental disorders pre and post implant DBS (Deep Brain Stimulation) through a Neuropsychological Assessment (NA). Casuistics and Method: This is a descriptive study in which patients with PD, candidates and submitted to implantation of DBS have participated. NA was performed in these patients before and after implantation of DBS with the following instruments: Wechsler Adult Intelligence Scale; Trail Making Test - Form A and B; Stroop Test; Boston Naming Test; Hooper Visual Organization Test; Wechsler Memory Scale-Revised (WMS-R); Rey Complex Figure; Rey Auditory Verbal Learning Test (RAVLT); Wisconsin Card Sorting Test (WCST) and Beck´s Depression and Anxiety Inventory . Results: From the 29 patients evaluated; the mean age was 60.2 (± 9.35) years , mainly males (n = 19), married (n = 21), with complete primary education (n = 22) and retired ( n = 24). The average time of diagnosis was 11.37 years (± 5.47), the mean age of onset 48.63 (± 7.36). The stage of PD was light to moderate. Clinical evaluation showed significant differences pre and post DBS, with improvement in symptoms. The NA has identified improvement after DBS overall intelligence quotient (p = 0.0022), in activities related to processing speed, and symptoms of mental disorders: depression (p <0.0001), anxiety (p = 0.0038) and apathy (p <0.001). Worsening after DBS was Identified in executive function, memory and verbal fluency. Conclusions: After DBS implantation, there was improvement in symptoms of depression, anxiety and apathy. In general, there was no improvement in cognitive function. / Introdução: Doença de Parkinson (DP) é uma doença crônica progressiva, que compromete aspectos físicos, cognitivos e emocionais. Objetivo: O objetivo deste estudo foi avaliar a ocorrência de alterações na cognição e nos sintomas de transtornos mentais pré e pós implante de DBS (Deep Brain Stimulation) por meio de uma avaliação neuropsicológica (AN). Casuística e Método: Estudo descritivo, no qual participaram pacientes com DP, candidatos e submetidos ao implante de DBS. Foi realizada AN nos pacientes pré e pós implante de DBS com os seguintes instrumentos: Wechsler Adult Intelligence Scale; Trail Making Test - Forma A e B; Stroop Test; Boston Naming Test; Hooper Visual Organization Test; Wechsler Memory Scale- Revised (WMS-R); Figura Complexa de Rey; Rey Auditory Verbal Learning Test (RAVLT); Wisconsin Cards Sorting Test (WCST) e Escalas de Depressão e de Ansiedade de Beck. Resultados: Dos 29 pacientes avaliados, a média de idade foi 60,2 (± 9,35) anos, eram principalmente do sexo masculino (n=19), casados (n=21), com ensino fundamental completo (n=22) e aposentados (n=24). O tempo médio de diagnóstico da doença foi 11,37 anos (± 5,47), a média de idade de início 48,63 (± 7,36). O estágio da DP era leve a moderado. A avaliação clínica indicou diferença significante pré e pós DBS, com melhora dos sintomas. A AN identificou melhora pós DBS no quociente intelectual geral (p=0,0022), nas atividades relacionadas à velocidade de processamento, e nos sintomas de transtornos mentais: depressão (p<0,0001), ansiedade (p=0,0038) e apatia (p<0,001). Identificou piora pós DBS na função executiva, memória e fluência verbal. Conclusões: Após o implante de DBS houve melhora dos sintomas de depressão, ansiedade e apatia. Não houve melhora da função cognitiva em geral.

Atualmente se tem bem estabelecido o tratamento para Doença de Parkinson, dentre eles o DBS (Deep Brain Stimulation). Embora haja controvérsias, muitos estudos têm demonstrado os efeitos adversos do DBS sobre a cognição, humor e comportamento. Assim, este estudo buscou investigar a associação entre os prejuízos cognitivos no pós-operatório e a volumetria cerebral em pacientes parkinsonianos submetidos a DBS, verificando se a correlação entre ambos pode ser considerada fator de risco para os prejuízos encontrados no pós-operatório. Fizeram parte da população estudada 25 indivíduos, 80% do sexo masculino, que foram submetidos ao procedimento cirúrgico de estimulação cerebral profunda (DBS) no Hospital de Clínicas de Porto Alegre (HCPA), em Porto Alegre entre 2012 e 2015. Estes sujeitos foram submetidos a uma bateria de testes cognitivos, bem como a testes clínicos e a ressonância magnética computadorizada nos períodos pré e pós-operatório em 6 meses. Os dados foram analisados através de estatísticas descritivas, coeficiente de correlação de Pearson e Teste t. Os resultados serão considerados significativos a um nível de significância máximo de 5% (p≤ 0,05) e o software estatístico utilizado para a análise será o SPSS versão 20.0. Quanto aos aspectos cognitivos avaliados, somente a fluência verbal fonêmica mostrou redução significativa entre os períodos pré e pós-operatório (p=0,003). A transfixação dos ventrículos foi associada à perda na fluência verbal semântica (p=0,009) e na memória (p=0,016) no pós-operatório. A presença de lesão na substância branca foi associada ao maior prejuízo na função executiva (p=0,017), fluência verbal semântica (p=0,039) e memória (p=0,050). Conclusão: Os prejuízos na fluência verbal semântica e memória no pós-operatório foram associados à presença de lesão na substância branca e a transfixação dos ventrículos pelo cabo com 6 eletrodos. A perda na função executiva foi associada a presença de lesão na substância branca. Os danos na fluência verbal fonêmica no pós-operatório, embora difiram estatisticamente, não foram associados a quaisquer achados da RM. / Currently, the treatment for Parkinson's Disease has been well established, among them DBS (Deep Brain Stimulation). Although controversial, many studies have demonstrated the adverse effects of DBS on cognition, mood, and behavior. Thus, this study sought to investigate the association between cognitive impairment in the postoperative period and cerebral volume in patients with Parkinson's disease who underwent DBS, and whether the correlation between the two can be considered as a risk factor for the possible postoperative losses. Twenty-five subjects, 80% male, who underwent deep brain stimulation (DBS) at the Hospital de Clínicas in Porto Alegre, Porto Alegre, between 2012 and 2015, were submitted to a cognitive battery, as well as clinical trials and computerized magnetic resonance imaging in the preoperative and postoperative periods at 6 months. Data were analyzed through descriptive statistics, Pearson's correlation coefficient and t-test. The results will be considered significant at a maximum significance level of 5% (p≤0.05) and the statistical software used for analysis will be SPSS version 20.0. Concerning the cognitive aspects evaluated, only phonemic verbal fluency showed a significant reduction between the pre and postoperative periods (p = 0.003). The transfixation of the ventricles was associated with loss of semantic verbal fluency (p = 0.009) and memory (p = 0.016) in the postoperative period. The presence of lesion in the white matter was associated with greater impairment in executive function (p = 0.017), semantic verbal fluency (p = 0.039) and memory (p = 0.050). Conclusion: The losses in the semantic verbal fluency and memory in the postoperative period were associated with the presence of white matter lesion and the transfixation of the ventricles by the cable with electrodes. The loss of executive function was associated with the presence of injury in the white matter. Damage to phonemic verbal fluency in 8 the postoperative period, although statistically different, was not associated with any MRI findings.

Atualmente se tem bem estabelecido o tratamento para Doença de Parkinson, dentre eles o DBS (Deep Brain Stimulation). Embora haja controvérsias, muitos estudos têm demonstrado os efeitos adversos do DBS sobre a cognição, humor e comportamento. Assim, este estudo buscou investigar a associação entre os prejuízos cognitivos no pós-operatório e a volumetria cerebral em pacientes parkinsonianos submetidos a DBS, verificando se a correlação entre ambos pode ser considerada fator de risco para os prejuízos encontrados no pós-operatório. Fizeram parte da população estudada 25 indivíduos, 80% do sexo masculino, que foram submetidos ao procedimento cirúrgico de estimulação cerebral profunda (DBS) no Hospital de Clínicas de Porto Alegre (HCPA), em Porto Alegre entre 2012 e 2015. Estes sujeitos foram submetidos a uma bateria de testes cognitivos, bem como a testes clínicos e a ressonância magnética computadorizada nos períodos pré e pós-operatório em 6 meses. Os dados foram analisados através de estatísticas descritivas, coeficiente de correlação de Pearson e Teste t. Os resultados serão considerados significativos a um nível de significância máximo de 5% (p≤ 0,05) e o software estatístico utilizado para a análise será o SPSS versão 20.0. Quanto aos aspectos cognitivos avaliados, somente a fluência verbal fonêmica mostrou redução significativa entre os períodos pré e pós-operatório (p=0,003). A transfixação dos ventrículos foi associada à perda na fluência verbal semântica (p=0,009) e na memória (p=0,016) no pós-operatório. A presença de lesão na substância branca foi associada ao maior prejuízo na função executiva (p=0,017), fluência verbal semântica (p=0,039) e memória (p=0,050). Conclusão: Os prejuízos na fluência verbal semântica e memória no pós-operatório foram associados à presença de lesão na substância branca e a transfixação dos ventrículos pelo cabo com 6 eletrodos. A perda na função executiva foi associada a presença de lesão na substância branca. Os danos na fluência verbal fonêmica no pós-operatório, embora difiram estatisticamente, não foram associados a quaisquer achados da RM. / Currently, the treatment for Parkinson's Disease has been well established, among them DBS (Deep Brain Stimulation). Although controversial, many studies have demonstrated the adverse effects of DBS on cognition, mood, and behavior. Thus, this study sought to investigate the association between cognitive impairment in the postoperative period and cerebral volume in patients with Parkinson's disease who underwent DBS, and whether the correlation between the two can be considered as a risk factor for the possible postoperative losses. Twenty-five subjects, 80% male, who underwent deep brain stimulation (DBS) at the Hospital de Clínicas in Porto Alegre, Porto Alegre, between 2012 and 2015, were submitted to a cognitive battery, as well as clinical trials and computerized magnetic resonance imaging in the preoperative and postoperative periods at 6 months. Data were analyzed through descriptive statistics, Pearson's correlation coefficient and t-test. The results will be considered significant at a maximum significance level of 5% (p≤0.05) and the statistical software used for analysis will be SPSS version 20.0. Concerning the cognitive aspects evaluated, only phonemic verbal fluency showed a significant reduction between the pre and postoperative periods (p = 0.003). The transfixation of the ventricles was associated with loss of semantic verbal fluency (p = 0.009) and memory (p = 0.016) in the postoperative period. The presence of lesion in the white matter was associated with greater impairment in executive function (p = 0.017), semantic verbal fluency (p = 0.039) and memory (p = 0.050). Conclusion: The losses in the semantic verbal fluency and memory in the postoperative period were associated with the presence of white matter lesion and the transfixation of the ventricles by the cable with electrodes. The loss of executive function was associated with the presence of injury in the white matter. Damage to phonemic verbal fluency in 8 the postoperative period, although statistically different, was not associated with any MRI findings.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a resting tremor combined with varying degrees of rigidity and bradykinesia. Introduced in the 1950s, thalamotomy is used as a surgical procedure to improve brain function in patients and serves as an effective treatment method for the PD tremor where connections within the thalamus are cut. In 1987, deep brain stimulation (DBS), chronic electrical stimulation of deep neural structures using electrodes, was introduced as a clinical treatment for medically refractory tremor in patients with PD. Though thalamotomy has historically been the primary treatment method for PD, an increasing number of patients have chosen to undergo DBS as it has become increasingly touted as an alternative to ablative therapies. The proposed study examines the advantages and disadvantages of both treatment methods to improve cardinal features in highly-skilled, career-oriented PD patients who actively use motor functions in their work. As an alternative to a simple finger-tapping test used for normal PD patients, a more complex strength-dexterity (S-D) test would be performed on 50 skilled patients to evaluate and compare the effectiveness of tremor suppression between both surgeries. The goal of this experiment is to determine which treatment produces the most short-term benefits for the patient to continue with his or her career with minimal future management required. The results of this study will help determine the preferred treatment method when taking into consideration other external factors such as cost, continual management, and preference for short-term vs. long-term results.

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.

The in-vivo observation of the neural activities generated by a large number of closely located neurons is believed to be crucial for understanding the nervous system. Moreover, the functional electrical stimulation of the central nervous system is an effective method to restore physiological functions such as limb control, sound sensation, and light perception. The Deep Brain Stimulation (DBS) is being successfully used in the treatment of tremor and rigidity associated with advanced Parkinson's disease. Cochlear implants have also been employed as an effective treatment for sensorineural deafness by means of delivering the electrical stimulation directly to the auditory nerve. The most significant contribution of this PhD study is the development of next-generation microprobes for the simultaneous stimulation and recording of the cortex and deep brain structures. For intracortical applications, millimetre length multisite microprobes that are rigid enough to penetrate into the cortex while integrated with flexible interconnection cables are demanded. In chronic applications, the flexibility of the cable minimizes the tissue damage caused by the relative micro-motion between the brain and the microprobe. Although hybrid approaches have been reported to construct such neural microprobes, these devices are brittle and may impose severe complications if they break inside the tissue. In this project, MEMS fabrication processes were employed to produce non-breakable intracortical microprobes with an improved structural design. These 32 channel devices are integrated with flexible interconnection cables and provide enough mechanical strength for penetration into the tissue. Polyimide-based flexible implants were successfully fabricated and locally reinforced at the tip with embedded 15 µm-thick gold micro-needles. In DBS applications, centimetre long microprobes capable of stimulating and recording the neural activity are required. The currently available DBS probes, manufactured by Medtronic, provide only four cylindrical shaped electrode sites, each 1.5 mm in height and 1.27 mm in diameter. Although suitable for the stimulation of a large brain volume, to measure the activity of a single neuron but to avoid measuring the average response of adjacent cells, recording sites with dimensions in the range of 10 - 20 µm are required. In this work, novel Three Dimensional (3D) multi channel microprobes were fabricated offering 32 independent stimulation and recording electrodes around the shaft of the implant. These microprobes can control the spatial distribution of the charge injected into the tissue to enhance the efficacy and minimize the adverse effects of the DBS treatment. Furthermore, the device volume has been reduced to one third the volume of a conventional Medtronic DBS lead to significantly decrease the tissue damage induced by implantation of the microprobe. For both DBS and intracortical microprobes, the impedance characteristics of the electrodes were studied in acidic and saline solutions. To reduce the channel impedance and enhance the signal to noise ratio, iridium (Ir) was electroplated on gold electrode sites. Stable electrical characteristics were demonstrated for the Ir and gold electrodes over the course of a prolonged pulse stress test for 100 million cycles. The functionality and application potential of the fabricated microprobes were confirmed by the in-vitro measurements of the neural activity in the mouse hippocampus. In order to reduce the number of channels and simplify the signal processing circuitry, multiport electrostatic-actuated switch matrices were successfully developed, fabricated, and characterized for possible integration with neural microprobes to construct a site selection matrix. Magnetic-actuated switches have been also investigated to improve the operation reliability of the MEMS switching devices.