Facilitating effects of deep brain stimulation on feedback learning in Parkinson's disease.

PubMed

Meissner, Sarah Nadine; Südmeyer, Martin; Keitel, Ariane; Pollok, Bettina; Bellebaum, Christian

2016-10-15

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides an effective treatment for Parkinson's disease (PD) motor symptoms. However, findings of effects on cognitive function such as feedback learning remain controversial and rare. The aim of the present study was to gain a better understanding of cognitive alterations associated with STN-DBS. Therefore, we investigated effects of STN-DBS on active and observational feedback learning in PD. 18 PD patients with STN-DBS and 18 matched healthy controls completed active and observational feedback learning tasks. Patients were investigated ON and OFF STN-DBS. Tasks consisted of learning (with feedback) and test phases (without feedback). STN-DBS improved active learning during feedback trials and PD patients ON (but not OFF) STN-DBS showed comparable performance patterns as healthy controls. No STN-DBS effect was found when assessing performance during active test trials without feedback. In this case, however, STN-DBS effects were found to depend on symptom severity. While more impaired patients benefited from STN-DBS, stimulation had no facilitating effect on patients with less severe symptoms. Along similar lines, the severity of motor symptoms tended to be significantly correlated with differences in active test performance due to STN-DBS. For observational feedback learning, there was a tendency for a positive STN-DBS effect with patients reaching the performance level of healthy controls only ON STN-DBS. The present data suggest that STN-DBS facilitates active feedback learning in PD patients. Furthermore, they provide first evidence that STN-DBS might not only affect learning from own but also from observed actions and outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

How to improve patient education on deep brain stimulation in Parkinson's disease: the CARE Monitor study.

PubMed

Dinkelbach, Lars; Möller, Bettina; Witt, Karsten; Schnitzler, Alfons; Südmeyer, Martin

2017-02-21

The introduction of deep brain stimulation (DBS) about 25 years ago provided one of the major breakthroughs in the treatment of Parkinson's disease (PD). However, a high percentage of patients are reluctant to undergo DBS. Previous research revealed that the critical step on the patient's path to DBS is the decision whether to undergo further diagnostic assessment for surgery at a specialized DBS-center. The aims of the current study were to evaluate how effective the combination of an outpatient DBS screening tool, STIMULUS, with specially developed educational material was to enhance patient education on DBS and to identify motivational aspects which influenced the patients' willingness to undergo further assessment. In total, 264 patients were identified as appropriate candidates for DBS by general neurologists using the electronic preselection tool STIMULUS. Patient-centered information material was designed and handed out to support education on DBS. Further, several clinical characteristics and details of the patient counseling were documented. Refusal or consent to show up at a DBS center was registered over the following 16 months. 114 (43.2%) patients preselected as eligible for DBS (STIMULUS Score ≥ 6) agreed to show up at a specialized DBS center to undergo further diagnostic assessment. The patients' ages, PD classification as an akinetic-rigid type and the talks' topics side-effects of dopaminergic medication and the optimal time frame had a significant influence on the patients' decisions. The combination of preselection tools as STIMULUS with comprehensive information material is effective to increase DBS-acceptance rate in PD patients. Important topics of the information about DBS cover the optimal time frame for DBS surgery, the side-effects of dopaminergic medication as well as side-effects and complications of DBS surgery.

A Python object-oriented framework for the CMS alignment and calibration data

NASA Astrophysics Data System (ADS)

Dawes, Joshua H.; CMS Collaboration

2017-10-01

The Alignment, Calibrations and Databases group at the CMS Experiment delivers Alignment and Calibration Conditions Data to a large set of workflows which process recorded event data and produce simulated events. The current infrastructure for releasing and consuming Conditions Data was designed in the two years of the first LHC long shutdown to respond to use cases from the preceding data-taking period. During the second run of the LHC, new use cases were defined. For the consumption of Conditions Metadata, no common interface existed for the detector experts to use in Python-based custom scripts, resulting in many different querying and transaction management patterns. A new framework has been built to address such use cases: a simple object-oriented tool that detector experts can use to read and write Conditions Metadata when using Oracle and SQLite databases, that provides a homogeneous method of querying across all services. The tool provides mechanisms for segmenting large sets of conditions while releasing them to the production database, allows for uniform error reporting to the client-side from the server-side and optimizes the data transfer to the server. The architecture of the new service has been developed exploiting many of the features made available by the metadata consumption framework to implement the required improvements. This paper presents the details of the design and implementation of the new metadata consumption and data upload framework, as well as analyses of the new upload service’s performance as the server-side state varies.

Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease.

PubMed

Wang, Xiao-Hong; Zhang, Lin; Sperry, Laura; Olichney, John; Farias, Sarah Tomaszewski; Shahlaie, Kiarash; Chang, Norika Malhado; Liu, Ying; Wang, Su-Ping; Wang, Cui

2015-12-20

This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD). We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus. We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

A proof-of-principle simulation for closed-loop control based on preexisting experimental thalamic DBS-enhanced instrumental learning.

PubMed

Wang, Ching-Fu; Yang, Shih-Hung; Lin, Sheng-Huang; Chen, Po-Chuan; Lo, Yu-Chun; Pan, Han-Chi; Lai, Hsin-Yi; Liao, Lun-De; Lin, Hui-Ching; Chen, Hsu-Yan; Huang, Wei-Chen; Huang, Wun-Jhu; Chen, You-Yin

Deep brain stimulation (DBS) has been applied as an effective therapy for treating Parkinson's disease or essential tremor. Several open-loop DBS control strategies have been developed for clinical experiments, but they are limited by short battery life and inefficient therapy. Therefore, many closed-loop DBS control systems have been designed to tackle these problems by automatically adjusting the stimulation parameters via feedback from neural signals, which has been reported to reduce the power consumption. However, when the association between the biomarkers of the model and stimulation is unclear, it is difficult to develop an optimal control scheme for other DBS applications, i.e., DBS-enhanced instrumental learning. Furthermore, few studies have investigated the effect of closed-loop DBS control for cognition function, such as instrumental skill learning, and have been implemented in simulation environments. In this paper, we proposed a proof-of-principle design for a closed-loop DBS system, cognitive-enhancing DBS (ceDBS), which enhanced skill learning based on in vivo experimental data. The ceDBS acquired local field potential (LFP) signal from the thalamic central lateral (CL) nuclei of animals through a neural signal processing system. A strong coupling of the theta oscillation (4-7 Hz) and the learning period was found in the water reward-related lever-pressing learning task. Therefore, the theta-band power ratio, which was the averaged theta band to averaged total band (1-55 Hz) power ratio, could be used as a physiological marker for enhancement of instrumental skill learning. The on-line extraction of the theta-band power ratio was implemented on a field-programmable gate array (FPGA). An autoregressive with exogenous inputs (ARX)-based predictor was designed to construct a CL-thalamic DBS model and forecast the future physiological marker according to the past physiological marker and applied DBS. The prediction could further assist the design of a closed-loop DBS controller. A DBS controller based on a fuzzy expert system was devised to automatically control DBS according to the predicted physiological marker via a set of rules. The simulated experimental results demonstrate that the ceDBS based on the closed-loop control architecture not only reduced power consumption using the predictive physiological marker, but also achieved a desired level of physiological marker through the DBS controller. Copyright © 2017 Elsevier Inc. All rights reserved.

Do capillary dried blood spot concentrations of gamma-hydroxybutyric acid mirror those in venous blood? A comparative study.

PubMed

Sadones, Nele; Archer, John R H; Ingels, Ann-Sofie M E; Dargan, Paul I; Wood, David M; Wood, Michelle; Neels, Hugo; Lambert, Willy E; Stove, Christophe P

2015-04-01

Gamma-hydroxybutyric acid (GHB) is a well-known illicit club and date-rape drug. Dried blood spot (DBS) sampling is a promising alternative for classical venous sampling in cases of (suspected) GHB intoxication since it allows rapid sampling, which is of interest for the extensively metabolized GHB. However, there is limited data if -and how- capillary DBS concentrations correlate with venous concentrations. We conducted a comparative study in 50 patients with suspected GHB intoxication, to determine and to correlate GHB concentrations in venous DBS (vDBS) and capillary DBS (cDBS). This is the first study that evaluates in a large cohort the correlation between capillary and venous concentrations of an illicit drug in real-life samples. Of the 50 paired samples, 7 were excluded: the vDBS concentration was below the LLOQ of 2 µg/mL in 3 cases and 4 samples were excluded after visual inspection of the DBS. Bland-Altman analysis revealed a mean % difference of -2.8% between cDBS and vDBS concentrations, with the zero value included in the 95% confidence interval of the mean difference in GHB concentration. A paired sample t-test confirmed this observation (p = 0.17). Also the requirement for incurred sample reproducibility was fulfilled: for more than two-thirds of the samples the concentrations obtained in cDBS and those in vDBS were within 20% of their mean. Since equivalent concentrations were observed in cDBS and vDBS, blood obtained by fingerprick can be considered a valid alternative for venous blood for GHB determination. Copyright © 2015 John Wiley & Sons, Ltd.

Failure to suppress low-frequency neuronal oscillatory activity underlies the reduced effectiveness of random patterns of deep brain stimulation.

PubMed

McConnell, George C; So, Rosa Q; Grill, Warren M

2016-06-01

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for the motor symptoms of Parkinson's disease (PD). However, the mechanisms of action of DBS are unknown. Random temporal patterns of DBS are less effective than regular DBS, but the neuronal basis for this dependence on temporal pattern of stimulation is unclear. Using a rat model of PD, we quantified the changes in behavior and single-unit activity in globus pallidus externa and substantia nigra pars reticulata during high-frequency STN DBS with different degrees of irregularity. Although all stimulus trains had the same average rate, 130-Hz regular DBS more effectively reversed motor symptoms, including circling and akinesia, than 130-Hz irregular DBS. A mixture of excitatory and inhibitory neuronal responses was present during all stimulation patterns, and mean firing rate did not change during DBS. Low-frequency (7-10 Hz) oscillations of single-unit firing times present in hemiparkinsonian rats were suppressed by regular DBS, and neuronal firing patterns were entrained to 130 Hz. Irregular patterns of DBS less effectively suppressed 7- to 10-Hz oscillations and did not regularize firing patterns. Random DBS resulted in a larger proportion of neuron pairs with increased coherence at 7-10 Hz compared with regular 130-Hz DBS, which suggested that long pauses (interpulse interval >50 ms) during random DBS facilitated abnormal low-frequency oscillations in the basal ganglia. These results suggest that the efficacy of high-frequency DBS stems from its ability to regularize patterns of neuronal firing and thereby suppress abnormal oscillatory neural activity within the basal ganglia. Copyright © 2016 the American Physiological Society.

Deep brain stimulation for the treatment of Alzheimer disease and dementias.

PubMed

Laxton, Adrian W; Lozano, Andres M

2013-01-01

To review the use of deep brain stimulation (DBS) for treatment of dementia. A PubMed literature search was conducted to identify all studies that have investigated the use of DBS for treatment of dementia. Three studies examined the use of DBS for dementia. One study involved fornix DBS for Alzheimer disease (AD), and two studies involved DBS of the nucleus basalis of Meynert, one to treat AD and one to treat Parkinson disease dementia. Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of dried blood spot protocols with the Bio-Rad GS HIV Combo Ag/Ab EIA and Geenius™ HIV 1/2 Supplemental Assay.

PubMed

Luo, Wei; Davis, Geoff; Li, LiXia; Shriver, M Kathleen; Mei, Joanne; Styer, Linda M; Parker, Monica M; Smith, Amanda; Paz-Bailey, Gabriela; Ethridge, Steve; Wesolowski, Laura; Owen, S Michele; Masciotra, Silvina

2017-06-01

FDA-approved antigen/antibody combo and HIV-1/2 differentiation supplemental tests do not have claims for dried blood spot (DBS) use. We compared two DBS-modified protocols, the Bio-Rad GS HIV Combo Ag/Ab (BRC) EIA and Geenius™ HIV-1/2 (Geenius) Supplemental Assay, to plasma protocols and evaluated them in the CDC/APHL HIV diagnostic algorithm. BRC-DBS p24 analytical sensitivity was calculated from serial dilutions of p24. DBS specimens included 11 HIV-1 seroconverters, 151 HIV-1-positive individuals, including 20 on antiretroviral therapy, 31 HIV-2-positive and one HIV-1/HIV-2-positive individuals. BRC-reactive specimens were tested with Geenius using the same DBS eluate. Matched plasma specimens were tested with BRC, an IgG/IgM immunoassay and Geenius. DBS and plasma results were compared using the McNemar's test. A DBS-algorithm applied to 348 DBS from high-risk individuals who participated in surveillance was compared to HIV status based on local testing algorithms. BRC-DBS detects p24 at a concentration 18 times higher than in plasma. In seroconverters, BRC-DBS detected more infections than the IgG/IgM immunoassay in plasma (p=0.0133), but fewer infections than BRC-plasma (p=0.0133). In addition, the BRC/Geenius-plasma algorithm identified more HIV-1 infections than the BRC/Geenius-DBS algorithm (p=0.0455). The DBS protocols correctly identified HIV status for established HIV-1 infections, including those on therapy, HIV-2 infections, and surveillance specimens. The DBS protocols exhibited promising performance and allowed rapid supplemental testing. Although the DBS algorithm missed some early infections, it showed similar results when applied to specimens from a high-risk population. Implementation of a DBS algorithm would benefit testing programs without capacity for venipuncture. Published by Elsevier B.V.

Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease

PubMed Central

Wang, Xiao-Hong; Zhang, Lin; Sperry, Laura; Olichney, John; Farias, Sarah Tomaszewski; Shahlaie, Kiarash; Chang, Norika Malhado; Liu, Ying; Wang, Su-Ping; Wang, Cui

2015-01-01

Objective: This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD). Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus. Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS. Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain. Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients. PMID:26668154

Deep brain stimulation for Parkinson's disease: recent trends and future direction.

PubMed

Fukaya, Chikashi; Yamamoto, Takamitsu

2015-01-01

To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson's disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed.

Bilateral adaptive deep brain stimulation is effective in Parkinson's disease.

PubMed

Little, Simon; Beudel, Martijn; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Hariz, Marwan; Neal, Spencer; Cheeran, Binith; Cagnan, Hayriye; Gratwicke, James; Aziz, Tipu Z; Pogosyan, Alex; Brown, Peter

2016-07-01

Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson's disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication. We applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features. UPDRS scores were 43% (p=0.04; Cohen's d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS. Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson's disease.

PubMed

Irmen, Friederike; Huebl, Julius; Schroll, Henning; Brücke, Christof; Schneider, Gerd-Helge; Hamker, Fred H; Kühn, Andrea A

2017-10-01

The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflict-induced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity. © The Author (2017). Published by Oxford University Press.

Storage and use of residual dried blood spots from state newborn screening programs.

PubMed

Olney, Richard S; Moore, Cynthia A; Ojodu, Jelili A; Lindegren, Mary Lou; Hannon, W Harry

2006-05-01

To provide current data for policy discussions and to assess future needs among newborn screening programs regarding the storage and use of residual dried blood spots (DBS) in the United States. An electronic questionnaire was administered to U.S. state health department laboratory directors in 2003. Responses were received from 49 of the 50 states. Approximately half of them stored residual DBS for more than 6 months, 57% did not have a written policy that determines how residual DBS can or cannot be used, and 16% informed parents that DBS might be retained. Residual DBS were used by 74% of respondents for evaluation of newborn screening tests, by 52% for clinical or forensic testing, and by 28% for epidemiologic studies. Use of DBS was reported more frequently by states with extended storage. When asked if they might participate in an anonymous multistate epidemiologic study by contributing unlinked DBS, 41% responded affirmatively. More states have used residual DBS for evaluating newborn screening tests than for epidemiologic studies. There is potential interest among states in using unlinked DBS for multistate studies and a need for written policies addressing all uses of residual DBS.

Modeling deep brain stimulation: point source approximation versus realistic representation of the electrode

NASA Astrophysics Data System (ADS)

Zhang, Tianhe C.; Grill, Warren M.

2010-12-01

Deep brain stimulation (DBS) has emerged as an effective treatment for movement disorders; however, the fundamental mechanisms by which DBS works are not well understood. Computational models of DBS can provide insights into these fundamental mechanisms and typically require two steps: calculation of the electrical potentials generated by DBS and, subsequently, determination of the effects of the extracellular potentials on neurons. The objective of this study was to assess the validity of using a point source electrode to approximate the DBS electrode when calculating the thresholds and spatial distribution of activation of a surrounding population of model neurons in response to monopolar DBS. Extracellular potentials in a homogenous isotropic volume conductor were calculated using either a point current source or a geometrically accurate finite element model of the Medtronic DBS 3389 lead. These extracellular potentials were coupled to populations of model axons, and thresholds and spatial distributions were determined for different electrode geometries and axon orientations. Median threshold differences between DBS and point source electrodes for individual axons varied between -20.5% and 9.5% across all orientations, monopolar polarities and electrode geometries utilizing the DBS 3389 electrode. Differences in the percentage of axons activated at a given amplitude by the point source electrode and the DBS electrode were between -9.0% and 12.6% across all monopolar configurations tested. The differences in activation between the DBS and point source electrodes occurred primarily in regions close to conductor-insulator interfaces and around the insulating tip of the DBS electrode. The robustness of the point source approximation in modeling several special cases—tissue anisotropy, a long active electrode and bipolar stimulation—was also examined. Under the conditions considered, the point source was shown to be a valid approximation for predicting excitation of populations of neurons in response to DBS.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

PubMed

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

PubMed Central

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

Movement-Related Discharge in the Macaque Globus Pallidus during High-Frequency Stimulation of the Subthalamic Nucleus

PubMed Central

Zimnik, Andrew J.; Nora, Gerald J.; Desmurget, Michel

2015-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an “informational lesion,” whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism. PMID:25740526

Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study.

PubMed

De Jesus, Sol; Almeida, Leonardo; Shahgholi, Leili; Martinez-Ramirez, Daniel; Roper, Jaimie; Hass, Chris J; Akbar, Umer; Wagle Shukla, Aparna; Raike, Robert S; Okun, Michael S

2018-01-01

Conventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach. The current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS. This pilot study compared biphasic pulses (BiP) versus conventional DBS pulses (ClinDBS). Eleven ET subjects with clinically optimized ventralis intermedius nucleus DBS were enrolled. Objective measures were obtained over 3 h while ON BiP stimulation. There was observed benefit in the Fahn-Tolosa Tremor Rating Scale (TRS) for BiP conditions when compared to the DBS off condition and to ClinDBS setting. Total TRS scores during the DBS OFF condition (28.5 IQR = 24.5-35.25) were significantly higher than the other time points. Following active DBS, TRS improved to (20 IQR = 13.8-24.3) at ClinDBS setting and to (16.5 IQR = 12-20.75) at the 3 h period ON BiP stimulation (p = 0.001). Accelerometer recordings revealed improvement in tremor at rest (χ 2  = 16.1, p = 0.006), posture (χ 2  = 15.9, p = 0.007) and with action (χ 2  = 32.1, p=<0.001) when comparing median total scores at ClinDBS and OFF DBS conditions to 3 h ON BiP stimulation. There were no adverse effects and gait was not impacted. BiP was safe, tolerable and effective on the tremor symptoms when tested up to 3 h. This study demonstrated the feasibility of applying a novel DBS waveform in the clinic setting. Larger prospective studies with longer clinical follow-up will be required. Copyright © 2017. Published by Elsevier Ltd.

Beneficial effects of replacing diet beverages with water on type 2 diabetic obese women following a hypo-energetic diet: A randomized, 24-week clinical trial.

PubMed

Madjd, Ameneh; Taylor, Moira A; Delavari, Alireza; Malekzadeh, Reza; Macdonald, Ian A; Farshchi, Hamid R

2017-01-01

To compare the effect of replacing diet beverages (DBs) with water or continuing to drink DBs in patients with type 2 diabetes during a 24-week weight loss program. The primary endpoint was the effect of intervention on weight over a 24-week period. The main secondary endpoints included anthropometric measurement and glucose and fat metabolism during the 24-week period. A total of 81 overweight and obese women with type 2 diabetes, who usually consumed DBs in their diet, were asked to either substitute water for DBs or continue drinking DBs five times per week after lunch for 24 weeks (DBs group) during a weight loss program. Compared with the DBs group, the water group had a greater decrease in weight (water, -6.40 ± 2.42 kg; DBs, -5.25 ± 1.60 kg; P = .006), in BMI (water, -2.49 ± 0.92 kg/m 2 ; DBs, -2.06 ± 0.62 kg/m 2 ; P = .006), in FPG (water, -1.63 ± 0.54 mmol/L; DBs, -1.29 ± 0.48 mmol/L, P = .005), in fasting insulin (water, -5.71 ± 2.30 m lU/mL; DBs, -4.16 ± 1.74 m lU/mL, P = .011), in HOMA IR (water, -3.20 ± 1.17; DBs, -2.48 ± 0.99, P = 003) and in 2 hour postprandial glucose (water, -1.67 ± 0.62 mmol/L; DBs, -1.35 ± 0.39 mmol/L; P = 0.027) over the 24-week period. However, there was no significant time × group interaction for waist circumference, lipid profiles and HbA1c within both groups over the 24-week period. Replacement of DBs with water after the main meal in obese adult women with type 2 diabetes may lead to more weight reduction during a weight loss program. © 2016 John Wiley & Sons Ltd.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Deep Brain Stimulation Reveals a Dissociation of Consummatory and Motivated Behaviour in the Medial and Lateral Nucleus Accumbens Shell of the Rat

PubMed Central

van der Plasse, Geoffrey; Schrama, Regina; van Seters, Sebastiaan P.; Vanderschuren, Louk J. M. J.

2012-01-01

Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa. PMID:22428054

Deep brain stimulation reveals a dissociation of consummatory and motivated behaviour in the medial and lateral nucleus accumbens shell of the rat.

PubMed

van der Plasse, Geoffrey; Schrama, Regina; van Seters, Sebastiaan P; Vanderschuren, Louk J M J; Westenberg, Herman G M

2012-01-01

Following the successful application of deep brain stimulation (DBS) in the treatment of Parkinson's disease and promising results in clinical trials for obsessive compulsive disorder and major depression, DBS is currently being tested in small patient-populations with eating disorders and addiction. However, in spite of its potential use in a broad spectrum of disorders, the mechanisms of action of DBS remain largely unclear and optimal neural targets for stimulation in several disorders have yet to be established. Thus, there is a great need to examine site-specific effects of DBS on a behavioural level and to understand how DBS may modulate pathological behaviour. In view of the possible application of DBS in the treatment of disorders characterized by impaired processing of reward and motivation, like addiction and eating disorders, we examined the effect of DBS of the nucleus accumbens (NAcc) on food-directed behavior. Rats were implanted with bilateral stimulation electrodes in one of three anatomically and functionally distinct sub-areas of the NAcc: the core, lateral shell (lShell) and medial shell (mShell). Subsequently, we studied the effects of DBS on food consumption, and the motivational and appetitive properties of food. The data revealed a functional dissociation between the lShell and mShell. DBS of the lShell reduced motivation to respond for sucrose under a progressive ratio schedule of reinforcement, mShell DBS, however, profoundly and selectively increased the intake of chow. DBS of the NAcc core did not alter any form of food-directed behavior studied. DBS of neither structure affected sucrose preference. These data indicate that the intake of chow and the motivation to work for palatable food can independently be modulated by DBS of subregions of the NAcc shell. As such, these findings provide important leads for the possible future application of DBS as a treatment for eating disorders such as anorexia nervosa.

Cognitive functioning in psychiatric disorders following deep brain stimulation.

PubMed

Bergfeld, Isidoor O; Mantione, Mariska; Hoogendoorn, Mechteld L C; Denys, Damiaan

2013-07-01

Deep brain stimulation (DBS) is routinely used as a treatment for treatment-refractory Parkinson's disease and has recently been proposed for psychiatric disorders such as Tourette syndrome (TS), obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Although cognitive deterioration has repeatedly been shown in patients with Parkinson's disease following DBS, the impact of DBS on cognitive functioning in psychiatric patients has not yet been reviewed. Reviewing the available literature on cognitive functioning following DBS in psychiatric patients. A systematic literature search in PubMed, EMBASE and Web of Science, last updated in September 2012, found 1470 papers. Abstracts were scrutinized and 26 studies examining cognitive functioning of psychiatric patients following DBS were included on basis of predetermined inclusion criteria. Twenty-six studies reported cognitive functioning of 130 psychiatric patients following DBS (37 TS patients, 56 OCD patients, 28 MDD patients, 6 patients with Alzheimer's disease, and 3 patients with other disorders). None of the studies reported substantial cognitive decline following DBS. On the contrary, 13 studies reported cognitive improvement following DBS. Preliminary results suggest that DBS in psychiatric disorders does not lead to cognitive decline. In selected cases cognitive functioning was improved following DBS. However, cognitive improvement cannot be conclusively attributed to DBS since studies are hampered by serious limitations. We discuss the outcomes in light of these limitations and offer suggestions for future work. Copyright © 2013 Elsevier Inc. All rights reserved.

Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns.

PubMed

McConnell, George C; So, Rosa Q; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M

2012-11-07

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.

Effective deep brain stimulation suppresses low frequency network oscillations in the basal ganglia by regularizing neural firing patterns

PubMed Central

McConnell, George C.; So, Rosa Q.; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M.

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson’s disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90Hz) improve motor symptoms, while low frequencies (<50Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high frequency DBS reversed motor symptoms and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high frequency DBS, but not low frequency DBS, reduced pathological low frequency oscillations (~9Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low frequency band to the stimulation frequency during high frequency DBS, but not during low frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high frequency DBS is more effective than low frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low frequency network oscillations with a regularized pattern of neuronal firing. PMID:23136407

Cognitive and Psychiatric Effects of STN versus GPi Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Wang, Jia-Wei; Zhang, Yu-Qing; Zhang, Xiao-Hua; Wang, Yun-Peng; Li, Ji-Ping; Li, Yong-Jie

2016-01-01

Deep brain stimulation (DBS) of either the subthalamic nucleus (STN) or the globus pallidus interna (GPi) can reduce motor symptoms in patients with Parkinson's disease (PD) and improve their quality of life. However, the effects of STN DBS and GPi DBS on cognitive functions and their psychiatric effects remain controversial. The present meta-analysis was therefore performed to clarify these issues. We searched the PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Other sources, including internet-based clinical trial registries and grey literature sources, were also searched. After searching the literature, two investigators independently performed literature screens to assess the quality of the included trials and to extract the data. The outcomes included the effects of STN DBS and GPi DBS on multiple cognitive domains, depression, anxiety, and quality of life. Seven articles related to four randomized controlled trials that included 521 participants were incorporated into the present meta-analysis. Compared with GPi DBS, STN DBS was associated with declines in selected cognitive domains after surgery, including attention, working memory and processing speed, phonemic fluency, learning and memory, and global cognition. However, there were no significant differences in terms of quality of life or psychiatric effects, such as depression and anxiety, between the two groups. A selective decline in frontal-subcortical cognitive functions is observed after STN DBS in comparison with GPi DBS, which should not be ignored in the target selection for DBS treatment in PD patients. In addition, compared to GPi DBS, STN DBS does not affect depression, anxiety, and quality of life.

Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration

PubMed Central

Ellefsen, Kayla N; da Costa, Jose Luiz; Concheiro, Marta; Anizan, Sebastien; Barnes, Allan J; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

2015-01-01

Background: DBS are an increasingly common clinical matrix. Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC–HRMS and 2D GC–MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens’ (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4–105.9 %CV) and were lower than in blood. Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed. PMID:26327184

DBS-LC-MS/MS assay for caffeine: validation and neonatal application.

PubMed

Bruschettini, Matteo; Barco, Sebastiano; Romantsik, Olga; Risso, Francesco; Gennai, Iulian; Chinea, Benito; Ramenghi, Luca A; Tripodi, Gino; Cangemi, Giuliana

2016-09-01

DBS might be an appropriate microsampling technique for therapeutic drug monitoring of caffeine in infants. Nevertheless, its application presents several issues that still limit its use. This paper describes a validated DBS-LC-MS/MS method for caffeine. The results of the method validation showed an hematocrit dependence. In the analysis of 96 paired plasma and DBS clinical samples, caffeine levels measured in DBS were statistically significantly lower than in plasma but the observed differences were independent from hematocrit. These results clearly showed the need for extensive validation with real-life samples for DBS-based methods. DBS-LC-MS/MS can be considered to be a good alternative to traditional methods for therapeutic drug monitoring or PK studies in preterm infants.

Web application for detailed real-time database transaction monitoring for CMS condition data

NASA Astrophysics Data System (ADS)

de Gruttola, Michele; Di Guida, Salvatore; Innocente, Vincenzo; Pierro, Antonio

2012-12-01

In the upcoming LHC era, database have become an essential part for the experiments collecting data from LHC, in order to safely store, and consistently retrieve, a wide amount of data, which are produced by different sources. In the CMS experiment at CERN, all this information is stored in ORACLE databases, allocated in several servers, both inside and outside the CERN network. In this scenario, the task of monitoring different databases is a crucial database administration issue, since different information may be required depending on different users' tasks such as data transfer, inspection, planning and security issues. We present here a web application based on Python web framework and Python modules for data mining purposes. To customize the GUI we record traces of user interactions that are used to build use case models. In addition the application detects errors in database transactions (for example identify any mistake made by user, application failure, unexpected network shutdown or Structured Query Language (SQL) statement error) and provides warning messages from the different users' perspectives. Finally, in order to fullfill the requirements of the CMS experiment community, and to meet the new development in many Web client tools, our application was further developed, and new features were deployed.

A Scalable Monitoring for the CMS Filter Farm Based on Elasticsearch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andre, J.M.; et al.

2015-12-23

A flexible monitoring system has been designed for the CMS File-based Filter Farm making use of modern data mining and analytics components. All the metadata and monitoring information concerning data flow and execution of the HLT are generated locally in the form of small documents using the JSON encoding. These documents are indexed into a hierarchy of elasticsearch (es) clusters along with process and system log information. Elasticsearch is a search server based on Apache Lucene. It provides a distributed, multitenant-capable search and aggregation engine. Since es is schema-free, any new information can be added seamlessly and the unstructured informationmore » can be queried in non-predetermined ways. The leaf es clusters consist of the very same nodes that form the Filter Farm thus providing natural horizontal scaling. A separate central” es cluster is used to collect and index aggregated information. The fine-grained information, all the way to individual processes, remains available in the leaf clusters. The central es cluster provides quasi-real-time high-level monitoring information to any kind of client. Historical data can be retrieved to analyse past problems or correlate them with external information. We discuss the design and performance of this system in the context of the CMS DAQ commissioning for LHC Run 2.« less

Deep Brain Stimulation, Continuity over Time, and the True Self.

PubMed

Nyholm, Sven; O'Neill, Elizabeth

2016-10-01

One of the topics that often comes up in ethical discussions of deep brain stimulation (DBS) is the question of what impact DBS has, or might have, on the patient's self. This is often understood as a question of whether DBS poses a threat to personal identity, which is typically understood as having to do with psychological and/or narrative continuity over time. In this article, we argue that the discussion of whether DBS is a threat to continuity over time is too narrow. There are other questions concerning DBS and the self that are overlooked in discussions exclusively focusing on psychological and/or narrative continuity. For example, it is also important to investigate whether DBS might sometimes have a positive (e.g., a rehabilitating) effect on the patient's self. To widen the discussion of DBS, so as to make it encompass a broader range of considerations that bear on DBS's impact on the self, we identify six features of the commonly used concept of a person's "true self." We apply these six features to the relation between DBS and the self. And we end with a brief discussion of the role DBS might play in treating otherwise treatment-refractory anorexia nervosa. This further highlights the importance of discussing both continuity over time and the notion of the true self.

Are Patients Ready for "EARLYSTIM"? Attitudes towards Deep Brain Stimulation among Female and Male Patients with Moderately Advanced Parkinson's Disease.

PubMed

Sperens, Maria; Hamberg, Katarina; Hariz, Gun-Marie

2017-01-01

Objective . To explore, in female and male patients with medically treated, moderately advanced Parkinson's disease (PD), their knowledge and reasoning about Deep Brain Stimulation (DBS). Methods . 23 patients with PD (10 women), aged 46-70, were interviewed at a mean of 8 years after diagnosis, with open-ended questions concerning their reflections and considerations about DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in Grounded Theory. Results . From the patients' narratives, the core category "Processing DBS: balancing symptoms, fears and hopes" was established. The patients were knowledgeable about DBS and expressed cautious and well considered attitudes towards its outcome but did not consider themselves ill enough to undergo DBS. They were aware of its potential side-effects. They considered DBS as the last option when oral medication is no longer sufficient. There was no difference between men and women in their reasoning and attitudes towards DBS. Conclusion . This study suggests that knowledge about the pros and cons of DBS exists among PD patients and that they have a cautious attitude towards DBS. Our patients did not seem to endorse an earlier implementation of DBS, and they considered that it should be the last resort when really needed.

Are Patients Ready for “EARLYSTIM”? Attitudes towards Deep Brain Stimulation among Female and Male Patients with Moderately Advanced Parkinson's Disease

PubMed Central

2017-01-01

Objective. To explore, in female and male patients with medically treated, moderately advanced Parkinson's disease (PD), their knowledge and reasoning about Deep Brain Stimulation (DBS). Methods. 23 patients with PD (10 women), aged 46–70, were interviewed at a mean of 8 years after diagnosis, with open-ended questions concerning their reflections and considerations about DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in Grounded Theory. Results. From the patients' narratives, the core category “Processing DBS: balancing symptoms, fears and hopes” was established. The patients were knowledgeable about DBS and expressed cautious and well considered attitudes towards its outcome but did not consider themselves ill enough to undergo DBS. They were aware of its potential side-effects. They considered DBS as the last option when oral medication is no longer sufficient. There was no difference between men and women in their reasoning and attitudes towards DBS. Conclusion. This study suggests that knowledge about the pros and cons of DBS exists among PD patients and that they have a cautious attitude towards DBS. Our patients did not seem to endorse an earlier implementation of DBS, and they considered that it should be the last resort when really needed. PMID:28458943

Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation.

PubMed

Etiévant, A; Oosterhof, C; Bétry, C; Abrial, E; Novo-Perez, M; Rovera, R; Scarna, H; Devader, C; Mazella, J; Wegener, G; Sánchez, C; Dkhissi-Benyahya, O; Gronfier, C; Coizet, V; Beaulieu, J M; Blier, P; Lucas, G; Haddjeri, N

2015-08-01

Although deep brain stimulation (DBS) shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K(+) buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum.

PubMed

Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E; Do Monte, Fabricio H; Quirk, Gregory J; Barreto-Estrada, Jennifer L

2016-11-01

Recent research in humans and rodents has explored the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VS) as a possible treatment for drug addiction. However, the optimum electrode placement and optimum DBS parameters have not been thoroughly studied. Here we varied stimulation sites and frequencies to determine whether DBS of the VS could facilitate the extinction of morphine-induced conditioned place preference in rats. Rats were implanted with DBS electrodes in the dorsal or ventral subregions of the VS and trained to the morphine conditioned place preference. Subsequently, rats received extinction sessions over 9 days, combined with 60 min of either high- (130 Hz) or low- (20 Hz) frequency DBS. To study circuit-wide activations after DBS of the VS, c-fos immunohistochemistry was performed in regions involved in the extinction of drug-seeking behaviors. High-frequency DBS of the dorsal-VS impaired both extinction training and extinction memory, whereas high-frequency DBS of the ventral-VS had no effect. In contrast, low-frequency DBS of the dorsal-VS strengthened extinction memory when tested 2 or 9 days after the cessation of stimulation. Both DBS frequencies increased c-fos expression in the infralimbic prefrontal cortex, but only low-frequency DBS increased c-fos expression in the basal amygdala and the medial portion of the central amygdala. Our results suggest that low-frequency (rather than high-frequency) DBS of the dorsal-VS strengthens extinction memory and may be a potential adjunct for extinction-based therapies for treatment-refractory opioid addiction. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation

PubMed Central

Schiefer, Terry K.; Matsumoto, Joseph Y.; Lee, Kendall H.

2011-01-01

The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson’s disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted. PMID:22084629

Systematic Review of the Use of Dried Blood Spots for Monitoring HIV Viral Load and for Early Infant Diagnosis

PubMed Central

Smit, Pieter W.; Sollis, Kimberly A.; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M.; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perriens, Joseph H.; Peeling, Rosanna W.

2014-01-01

Background Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. Methods and Findings Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52–100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78–100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. Conclusions Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. Trial Registration PROSPERO Registration #: CRD42013003621. PMID:24603442

Field study of dried blood spot specimens for HIV-1 drug resistance genotyping.

PubMed

Parry, C M; Parkin, N; Diallo, K; Mwebaza, S; Batamwita, R; DeVos, J; Bbosa, N; Lyagoba, F; Magambo, B; Jordan, M R; Downing, R; Zhang, G; Kaleebu, P; Yang, C; Bertagnolio, S

2014-08-01

Dried blood spots (DBS) are an alternative specimen type for HIV drug resistance genotyping in resource-limited settings. Data relating to the impact of DBS storage and shipment conditions on genotyping efficiency under field conditions are limited. We compared the genotyping efficiencies and resistance profiles of DBS stored and shipped at different temperatures to those of plasma specimens collected in parallel from patients receiving antiretroviral therapy in Uganda. Plasma and four DBS cards from anti-coagulated venous blood and a fifth card from finger-prick blood were prepared from 103 HIV patients with a median viral load (VL) of 57,062 copies/ml (range, 1,081 to 2,964,191). DBS were stored at ambient temperature for 2 or 4 weeks or frozen at -80 °C and shipped from Uganda to the United States at ambient temperature or frozen on dry ice for genotyping using a broadly sensitive in-house method. Plasma (97.1%) and DBS (98.1%) stored and shipped frozen had similar genotyping efficiencies. DBS stored frozen (97.1%) or at ambient temperature for 2 weeks (93.2%) and shipped at ambient temperature also had similar genotyping efficiencies. Genotyping efficiency was reduced for DBS stored at ambient temperature for 4 weeks (89.3%, P = 0.03) or prepared from finger-prick blood and stored at ambient temperature for 2 weeks (77.7%, P < 0.001) compared to DBS prepared from venous blood and handled similarly. Resistance profiles were similar between plasma and DBS specimens. This report delineates the optimal DBS collection, storage, and shipping conditions and opens a new avenue for cost-saving ambient-temperature DBS specimen shipments for HIV drug resistance (HIVDR) surveillances in resource-limited settings. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Effects of repeated deep brain stimulation on depressive- and anxiety-like behavior in rats: comparing entopeduncular and subthalamic nuclei.

PubMed

Creed, Meaghan C; Hamani, Clement; Nobrega, José N

2013-07-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi) has been routinely used for the treatment of some movement disorders. However, DBS may be associated with adverse psychiatric effects, such as depression, anxiety and impulsivity. To compare DBS applied to the entopeduncular nucleus (EPN; the rodent homolog of the GPi) and STN in terms of their effects on depressive- and anxiety-like behavior in rats. DBS was applied for 21 days (4 h a day) to either the STN or EPN. Rats then underwent behavioral testing on learned helplessness and elevated plus maze tasks before being sacrificed for brain analyses of zif268, BDNF and trkB mRNA as well as BDNF protein levels. Repeated DBS of the STN, but not of the EPN, led to impaired performance in the learned helplessness task, suggesting that STN-DBS induces or potentiates depressive-like behavior. There was no effect of DBS on elevated plus maze or on open field behavior. Repeated STN-DBS, but not EPN-DBS, led to decreased levels of BDNF and trkB mRNA in hippocampus. Acute stimulation of the STN or EPN resulted in similar changes in zif268 levels in several brain areas, except for the raphe where decreases were seen only after STB-DBS. Together these results indicate that the effects of STN- and EPN-DBS differ in behavioral and neurochemical respects. Results further suggest that the EPN may be a preferable target for clinical DBS when psychiatric side effects are considered insofar as it may be associated with a lower incidence of depressive-like behavior than the STN. Copyright © 2013 Elsevier Inc. All rights reserved.

Fragile X protein in newborn dried blood spots.

PubMed

Adayev, Tatyana; LaFauci, Giuseppe; Dobkin, Carl; Caggana, Michele; Wiley, Veronica; Field, Michael; Wotton, Tiffany; Kascsak, Richard; Nolin, Sarah L; Glicksman, Anne; Hosmer, Nicole; Brown, W Ted

2014-10-28

The fragile X syndrome (FXS) results from mutation of the FMR1 gene that prevents expression of its gene product, FMRP. We previously characterized 215 dried blood spots (DBS) representing different FMR1 genotypes and ages with a Luminex-based immunoassay (qFMRP). We found variable FMRP levels in the normal samples and identified affected males by the drastic reduction of FMRP. Here, to establish the variability of expression of FMRP in a larger random population we quantified FMRP in 2,000 anonymous fresh newborn DBS. We also evaluated the effect of long term storage on qFMRP by retrospectively assaying 74 aged newborn DBS that had been stored for 7-84 months that included normal and full mutation individuals. These analyses were performed on 3 mm DBS disks. To identify the alleles associated with the lowest FMRP levels in the fresh DBS, we analyzed the DNA in the samples that were more than two standard deviations below the mean. Analysis of the fresh newborn DBS revealed a broad distribution of FMRP with a mean approximately 7-fold higher than that we previously reported for fresh DBS in normal adults and no samples whose FMRP level indicated FXS. DNA analysis of the lowest FMRP DBS showed that this was the low extreme of the normal range and included a female carrying a 165 CGG repeat premutation. In the retrospective study of aged newborn DBS, the FMRP mean of the normal samples was less than 30% of the mean of the fresh DBS. Despite the degraded signal from these aged DBS, qFMRP identified the FXS individuals. The assay showed that newborn DBS contain high levels of FMRP that will allow identification of males and potentially females, affected by FXS. The assay is also an effective screening tool for aged DBS stored for up to four years.

Frequency-dependent, transient effects of subthalamic nucleus deep brain stimulation on methamphetamine-induced circling and neuronal activity in the hemiparkinsonian rat.

PubMed

So, Rosa Q; McConnell, George C; Grill, Warren M

2017-03-01

Methamphetamine-induced circling is used to quantify the behavioral effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in hemiparkinsonian rats. We observed a frequency-dependent transient effect of DBS on circling, and quantified this effect to determine its neuronal basis. High frequency STN DBS (75-260Hz) resulted in transient circling contralateral to the lesion at the onset of stimulation, which was not sustained after the first several seconds of stimulation. Following the transient behavioral change, DBS resulted in a frequency-dependent steady-state reduction in pathological ipsilateral circling, but no change in overall movement. Recordings from single neurons in globus pallidus externa (GPe) and substantia nigra pars reticulata (SNr) revealed that high frequency, but not low frequency, STN DBS elicited transient changes in both firing rate and neuronal oscillatory power at the stimulation frequency in a subpopulation of GPe and SNr neurons. These transient changes were not sustained, and most neurons exhibited a different response during the steady-state phase of DBS. During the steady-state, DBS produced elevated neuronal oscillatory power at the stimulus frequency in a majority of GPe and SNr neurons, and the increase was more pronounced during high frequency DBS than during low frequency DBS. Changes in oscillatory power during both transient and steady-state DBS were highly correlated with changes in firing rates. These results suggest that distinct neural mechanisms were responsible for transient and sustained behavioral responses to STN DBS. The transient contralateral turning behavior following the onset of high frequency DBS was paralleled by transient changes in firing rate and oscillatory power in the GPe and SNr, while steady-state suppression of ipsilateral turning was paralleled by sustained increased synchronization of basal ganglia neurons to the stimulus pulses. Our analysis of distinct frequency-dependent transient and steady-state responses to DBS lays the foundation for future mechanistic studies of the immediate and persistent effects of DBS. Copyright © 2016 Elsevier B.V. All rights reserved.

PyDBS: an automated image processing workflow for deep brain stimulation surgery.

PubMed

D'Albis, Tiziano; Haegelen, Claire; Essert, Caroline; Fernández-Vidal, Sara; Lalys, Florent; Jannin, Pierre

2015-02-01

Deep brain stimulation (DBS) is a surgical procedure for treating motor-related neurological disorders. DBS clinical efficacy hinges on precise surgical planning and accurate electrode placement, which in turn call upon several image processing and visualization tasks, such as image registration, image segmentation, image fusion, and 3D visualization. These tasks are often performed by a heterogeneous set of software tools, which adopt differing formats and geometrical conventions and require patient-specific parameterization or interactive tuning. To overcome these issues, we introduce in this article PyDBS, a fully integrated and automated image processing workflow for DBS surgery. PyDBS consists of three image processing pipelines and three visualization modules assisting clinicians through the entire DBS surgical workflow, from the preoperative planning of electrode trajectories to the postoperative assessment of electrode placement. The system's robustness, speed, and accuracy were assessed by means of a retrospective validation, based on 92 clinical cases. The complete PyDBS workflow achieved satisfactory results in 92 % of tested cases, with a median processing time of 28 min per patient. The results obtained are compatible with the adoption of PyDBS in clinical practice.

The Impact of Mirth-Inducing Ventral Striatal Deep Brain Stimulation on Functional and Effective Connectivity

PubMed Central

Gibson, William S; Cho, Shinho; Abulseoud, Osama A; Gorny, Krzysztof R; Felmlee, Joel P; Welker, Kirk M; Klassen, Bryan T; Min, Hoon-Ki; Lee, Kendall H

2017-01-01

Abstract Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is an investigational therapy for treatment-resistant obsessive-compulsive disorder. The ability of VC/VS DBS to evoke spontaneous mirth in patients, often accompanied by smiling and laughter, is clinically well documented. However, the neural correlates of DBS-evoked mirth remain poorly characterized. Patients undergoing VC/VS DBS surgery underwent intraoperative evaluation in which mirth-inducing and non-mirth-inducing stimulation localizations were identified. Using dynamic causal modeling (DCM) for fMRI, the effect of mirth-inducing DBS on functional and effective connectivity among established nodes in limbic cortico-striato-thalamo-cortical (CSTC) circuitry was investigated. Both mirth-inducing and non-mirth-inducing VC/VS DBS consistently resulted (conjunction, global null, family-wise error-corrected P < 0.05) in activation of amygdala, ventral striatum, and mediodorsal thalamus. However, only mirth-inducing DBS resulted in functional inhibition of anterior cingulate cortex. Dynamic causal modeling revealed that mirth-inducing DBS enhanced effective connectivity from anterior cingulate to ventral striatum, while attenuating connectivity from thalamus to ventral striatum relative to non-mirth-inducing stimulation. These results suggest that DBS-evoked mood elevation is accompanied by distinct patterns of limbic thalamocortical connectivity. Using the novel combination of DBS-evoked mood alteration and functional MRI in human subjects, we provide new insights into the network-level mechanisms that influence affect. PMID:27001680

Evaluation of HBsAg and anti-HBc assays in saliva and dried blood spot samples according HIV status.

PubMed

Flores, Geane Lopes; Cruz, Helena Medina; Potsch, Denise Vigo; May, Silvia Beatriz; Brandão-Mello, Carlos Eduardo; Pires, Marcia Maria Amendola; Pilotto, Jose Henrique; Lewis-Ximenez, Lia Laura; Lampe, Elisabeth; Villar, Livia Melo

2017-09-01

Influence of HIV status in HBV markers detection in saliva and dried blood spots (DBS) was not well established. This study aims to evaluate the performance of optimized commercial immunoassay for identifying HBsAg and anti-HBc in saliva and DBS according HIV status. A sum of 535 individuals grouped as HIV + , HBV + , HIV/HBV + and HIV/HBV- were recruited where 347 and 188 were included for HBsAg and anti-HBc evaluation, respectively. Serum, DBS collected in Whatman 903 paper and saliva obtained using salivette device were analyzed using EIA. Increased sample volume and ROC curve analysis for cut off determination were used for DBS and saliva testing. HBsAg detection in saliva and DBS exhibited sensitivities of 80.9% and 85.6% and specificities of 86.8% and 96.3%. Sensitivity of anti-HBc in saliva and DBS were 82.4% and 76.9% and specificities in saliva and DBS were 96.9% and 91.7%. Low sensitivities were observed for HBsAg (62%) and anti-HBc (47%) detection in saliva of HIV/HBV+ individuals. OD values were also lower for HBsAg detection in DBS and saliva of HIV/HBV+ individuals compared to their serum samples. Statistical significance was found for sensitivities in HBsAg detection between saliva and DBS demonstrating high sensitivity for DBS specimens. In conclusion, HIV status or antiretroviral treatment appears to interfere in the performance of HBsAg and anti-HBc detection in DBS and saliva samples using the adapted commercial EIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood-brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats.

PubMed

Chen, Ying-Chuan; Zhu, Guan-Yu; Wang, Xiu; Shi, Lin; Du, Ting-Ting; Liu, De-Feng; Liu, Yu-Ye; Jiang, Yin; Zhang, Xin; Zhang, Jian-Guo

2017-12-01

Objective The therapeutic efficacy of anterior thalamic nuclei deep brain stimulation (ATN-DBS) against seizures has been largely accepted; however, the effects of ATN-DBS on disruption of the blood-brain barrier (BBB), albumin extravasation, inflammation and apoptosis still remain unclear. Methods Rats were distributed into four treatment groups: physiological saline (PS, N = 12), kainic acid (KA, N = 12), KA-sham-DBS (N = 12) and KA-DBS (N = 12). Seizures were monitored using video-electroencephalogram (EEG). One day after surgery, all rats were sacrificed. Then, samples were prepared for quantitative real-time PCR (qPCR), western blot, immunofluorescence (IF) staining, and transmission electron microscopy to evaluate the disruption of the BBB, albumin extravasation, inflammation, and apoptosis. Result Because of the KA injection, the disruption of the BBB, albumin extravasation, inflammation and apoptosis were more severe in the KA and the KA-sham-DBS groups compared to the PS group (all Ps < 0.05 or < 0.01). The ideal outcomes were observed in the KA-DBS group. ATN-DBS produced a 46.3% reduction in seizure frequency and alleviated the disruption of the BBB, albumin extravasation, inflammatory reaction and apoptosis in comparison to the KA-sham-DBS group (all Ps < 0.05 or < 0.01). Conclusion (1) Seizures can be reduced using ATN-DBS in the epileptogenic stage. (2) ATN-DBS can reduce the disruption of the BBB and albumin extravasation. (3) ATN-DBS has an anti-inflammatory effect in epileptic models.

Quantitation of 25-hydroxyvitamin D in dried blood spots by 2D LC-MS/MS without derivatization and correlation with serum in adult and pediatric studies.

PubMed

Jensen, Berit P; Saraf, Rajneeta; Ma, Jing; Berry, Sarah; Grant, Cameron C; Camargo, Carlos A; Sies, Christiaan W

2018-06-01

Demand for measurement of 25-hydroxyvitamin D (25OHD) is growing and dried blood spot (DBS) sampling is attractive as samples are easier to collect, transport and store. A 2D LC-MS/MS assay without derivatization was developed. DBS punches (3.2 mm) were ultrasonicated with d 6 -25OHD 3 in 70% methanol followed by hexane extraction, dry-down and reconstitution. The assay was validated and applied to two studies comparing whole blood adult DBS with serum samples (n = 40) and neonatal whole blood DBS with cord serum samples (n = 80). The assay was validated in whole blood DBS over the range 13-106 nmol/L 25OHD 3 and 11-91 nmol/L 25OHD 2 with a limit of detection of 3 nmol/L. Intra- and inter-day imprecision was <13% CV and bias <12%. The assay had high recovery and minimal matrix effects. Triplicate DBS study samples had a mean CV of ≤13% for 25OHD 3. No 25OHD 2 was detected. DBS calculated serum 25OHD 3 concentrations correlated strongly with serum concentrations in the adult DBS/serum study (r = 0.94) and moderately in the neonatal DBS/cord serum study (r = 0.69). Direct quantitation of 25OHD in DBS by 2D LC-MS/MS without derivatization was found to be an alternative to serum quantitation applicable to clinical research studies on adult DBS samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.

PubMed

Ganguli, Malika P; Upton, Adrian R M; Kamath, Markad V

2017-01-01

Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

PubMed

Leblois, Arthur; Reese, René; Labarre, David; Hamann, Melanie; Richter, Angelika; Boraud, Thomas; Meissner, Wassilios G

2010-05-01

Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers. Copyright 2010 Elsevier Inc. All rights reserved.

Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting.

PubMed

Swan, Brandon D; Brocker, David T; Hilliard, Justin D; Tatter, Stephen B; Gross, Robert E; Turner, Dennis A; Grill, Warren M

2016-02-01

We conducted intraoperative measurements of tremor during DBS containing short pauses (⩽50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. All patterns of DBS decreased tremor relative to 'off'. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

PubMed

Humphries, Mark D; Gurney, Kevin

2012-07-01

Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

No Effect of Subthalamic Deep Brain Stimulation on Intertemporal Decision-Making in Parkinson Patients123

PubMed Central

Wojtecki, Lars; Storzer, Lena; Schnitzler, Alfons

2016-01-01

Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for the motor symptoms of Parkinson’s disease (PD). DBS or pharmacological treatment is believed to modulate the tendency to, or reverse, impulse control disorders. Several brain areas involved in impulsivity and reward valuation, such as the prefrontal cortex and striatum, are linked to the STN, and activity in these areas might be affected by STN-DBS. To investigate the effect of STN-DBS on one type of impulsive decision-making—delay discounting (i.e., the devaluation of reward with increasing delay until its receipt)—we tested 40 human PD patients receiving STN-DBS treatment and medication for at least 3 months. Patients were pseudo-randomly assigned to one of four groups to test the effects of DBS on/off states as well as medication on/off states on delay discounting. The delay-discounting task consisted of a series of choices among a smaller. sooner or a larger, later monetary reward. Despite considerable effects of DBS on motor performance, patients receiving STN-DBS did not choose more or less impulsively compared with those in the off-DBS group, as well as when controlling for risk attitude. Although null results have to be interpreted with caution, our findings are of significance to other researchers studying the effects of PD treatment on impulsive decision-making, and they are of clinical relevance for determining the therapeutic benefits of using STN-DBS. PMID:27257622

Treating post-traumatic tremor with deep brain stimulation: report of five cases.

PubMed

Issar, Neil M; Hedera, Peter; Phibbs, Fenna T; Konrad, Peter E; Neimat, Joseph S

2013-12-01

Post-traumatic tremor is one of the most common movement disorders resulting from severe head trauma. However, literature regarding successful deep brain stimulation (DBS) treatment is scarce, resulting in ambiguity regarding the optimal lead location. Most cases support the ventral intermediate nucleus, but there is evidence to defend DBS of the zona incerta, ventral oralis anterior/posterior, and/or a combination of these targets. We report five patients with disabling post-traumatic tremor treated with DBS of the ventral intermediate nucleus and of the globus pallidus internus. Patients were referred to the Vanderbilt Movement Disorders Division, and surgical intervention was determined by a DBS Multidisciplinary Committee. Standard DBS procedure was followed. Patients 1-4 sustained severe diffuse axonal injuries. Patients 1-3 underwent unilateral ventral intermediate nucleus DBS for contralateral tremor, while Patient 4 underwent bilateral ventral intermediate nucleus DBS. Patients 1-3 experienced good tremor reduction, while Patient 4 experienced moderate tremor reduction with some dystonic posturing of the hands. Patient 5 had dystonic posturing of the right upper extremity with tremor of the left upper extremity. He was treated with bilateral DBS of the globus pallidus internus and showed good tremor reduction at follow-up. Unilateral or bilateral DBS of the ventral intermediate nucleus and bilateral DBS of the globus pallidus internus may be effective and safe treatment modalities for intractable post-traumatic tremor. Further studies are needed to clarify the optimal target for surgical treatment of post-traumatic tremor. Published by Elsevier Ltd.

Adaptive deep brain stimulation in advanced Parkinson disease.

PubMed

Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

2013-09-01

Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

Rejecting deep brain stimulation artefacts from MEG data using ICA and mutual information.

PubMed

Abbasi, Omid; Hirschmann, Jan; Schmitz, Georg; Schnitzler, Alfons; Butz, Markus

2016-08-01

Recording brain activity during deep brain stimulation (DBS) using magnetoencephalography (MEG) can potentially help clarifying the neurophysiological mechanism of DBS. The DBS artefact, however, distorts MEG data significantly. We present an artefact rejection approach to remove the DBS artefact from MEG data. We developed an approach consisting of four consecutive steps: (i) independent component analysis was used to decompose MEG data to independent components (ICs); (ii) mutual information (MI) between stimulation signal and all ICs was calculated; (iii) artefactual ICs were identified by means of an MI threshold; and (iv) the MEG signal was reconstructed using only non-artefactual ICs. This approach was applied to MEG data from five Parkinson's disease patients with implanted DBS stimulators. MEG was recorded with DBS ON (unilateral stimulation of the subthalamic nucleus) and DBS OFF during two experimental conditions: a visual attention task and alternating right and left median nerve stimulation. With the presented approach most of the artefact could be removed. The signal of interest could be retrieved in both conditions. In contrast to existing artefact rejection methods for MEG-DBS data (tSSS and S(3)P), the proposed method uses the actual artefact source, i.e. the stimulation signal, as reference signal. Using the presented method, the DBS artefact can be significantly rejected and the physiological data can be restored. This will facilitate research addressing the impact of DBS on brain activity during rest and various tasks. Copyright © 2016 Elsevier B.V. All rights reserved.

Gait and Balance in Essential Tremor: Variable Effects of Bilateral Thalamic Stimulation

PubMed Central

Earhart, Gammon M.; Clark, B. Ruth; Tabbal, Samer D.; Perlmutter, Joel S.

2010-01-01

Essential tremor (ET) is a multi-faceted condition best known for postural and action tremor but also may include disordered gait and postural instability. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus provides substantial tremor reduction yet some patients with bilateral VIM DBS have gait and balance impairment. This study examines gait and balance performance in 13 participants with ET who have bilateral VIM DBS compared to a matched control group. Participants with ET were tested with their stimulators off (DBS OFF) and on (DBS ON). For both standard and tandem walking, participants with ET walked significantly more slowly than controls, with significantly lower cadence, spending a lower percentage of the gait cycle in single limb support and a higher percentage in double support compared to controls. Participants with ET also had significantly lower tandem and one leg stance times, Berg balance scores, balance confidence, and required significantly greater time to perform the Timed Up-and-Go relative to controls. There were no significant differences in any gait or balance measures in the DBS OFF versus DBS ON conditions, but the effects of DBS on gait and balance were highly variable among individuals. Future studies are needed to determine why some individuals experience gait and balance difficulties after bilateral thalamic DBS and others do not. A better understanding of the mechanisms underlying gait and balance impairments in those with bilateral DBS is critical in order to reduce falls and fractures in this group. PMID:19006189

Artistic creativity and DBS: a case report.

PubMed

Drago, V; Foster, P S; Okun, M S; Haq, I; Sudhyadhom, A; Skidmore, F M; Heilman, K M

2009-01-15

Deep brain stimulation (DBS) is a treatment for patients with Parkinson's disease (PD) who are not adequately controlled with medications. An artist reported changes in her artistic creativity and art appreciation when treated with left DBS. We sought to study her artistic productions and her appreciation of art while both "on" and "off" left DBS. A 69-year-old right-handed woman with an approximate 20-year history of PD was referred to us for management of a left subthalamic region nucleus (STN) DBS placed at another institution 4 years prior. In Experiment 1 we had her rate several dimensions (Evocative Impact, Aesthetics, Novelty, Technique, Closure and Representation) of another artist's paintings. In Experiment 2, we tested her with the Abbreviated Torrance Test (of creativity) for Adults (ATTA). During testing the patient remained on her dopaminergic medication, but was tested on and off left DBS. On the judgment task while "on" left DBS, versus "off" DBS, there were significant reductions in her appreciation of artistic Closure and Technique. When "off" DBS her ATTA creativity index was above average, but when switched "on" her creativity index was below average. These results suggest the possibility that left ventral STN/SNR DBS reduces creativity as well as appreciation of art. The reason for these alterations is not known, but might be related to enhanced activation of the left hemisphere and reciprocal deactivation of the right hemisphere which mediates both visuospatial skills and global attention, both of which are important in artistic creativity and appreciation.

Dried blood spot HIV-1 RNA quantification using open real-time systems in South Africa and Burkina Faso.

PubMed

Viljoen, Johannes; Gampini, Sandrine; Danaviah, Sivapragashini; Valéa, Diane; Pillay, Sureshnee; Kania, Dramane; Méda, Nicolas; Newell, Marie-Louise; Van de Perre, Philippe; Rouet, François

2010-11-01

There is an urgent need to assess the accuracy/feasibility of using dried blood spots (DBS) for monitoring of HIV-1 viral load in resource-limited settings. A total of 892 DBS from HIV-1-positive pregnant women and their neonates enrolled in the Kesho Bora prevention of mother-to-child transmission trial conducted in Durban (South Africa) and Bobo-Dioulasso (Burkina Faso) between May 2005 and July 2008 were tested for HIV-1 RNA. The combination Nuclisens extraction method (BioMérieux)/Generic HIV Viral Load assay (Biocentric) was performed using one DBS (in Durban) versus 2 DBS (in Bobo-Dioulasso) on 2 distinct open real-time polymerase chain reaction instruments. DBS HIV-1 RNA results were compared with plasma HIV-1 RNA and HIV serology results used as the gold standards. The limits of detection of assays on DBS were 3100 and 1550 copies per milliliter in Durban and Bobo-Dioulasso, respectively. DBS HIV-1 RNA values correlated significantly with plasma levels (n = 327; R = 0.7351) and were uniformly distributed according to duration of DBS storage at -20°C (median duration, 280 days). For early infant diagnosis, the sensitivity and specificity were 100% (95% confidence interval: 97.2 to 100.0 and 96.5 to 100.0, respectively). HIV-1 viral load kinetics in DNase-pretreated DBS were similar to those obtained in plasma specimens among 13 patients receiving antiretroviral treatment. HIV-1 RNA findings from serial infant DBS collected prospectively (n = 164) showed 100% concordance with HIV serology at 18 months of life. Our findings strongly advocate the implementation of DBS HIV-1 RNA testing in remote areas from low-income and middle-income countries.

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

PubMed

Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

2018-06-29

To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT ( p = 0.001). These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series

PubMed Central

Lenartz, Doris; Kuhn, Jens; Sturm, Volker

2016-01-01

Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31–48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed “partial response” on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders. PMID:27504631

Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait.

PubMed

Fleury, Vanessa; Pollak, Pierre; Gere, Julien; Tommasi, Giorgio; Romito, Luigi; Combescure, Christophe; Bardinet, Eric; Chabardes, Stephan; Momjian, Shahan; Krainik, Alexandre; Burkhard, Pierre; Yelnik, Jérôme; Krack, Paul

2016-09-01

Gait and akinesia deterioration in PD patients during the immediate postoperative period of DBS has been directly related to stimulation in the subthalamic region. The underlying mechanisms remain poorly understood. The aim of the present study was to clinically and anatomically describe this side effect. PD patients presenting with a worsening of gait and/or akinesia following STN-DBS, that was reversible on stimulation arrest were included. The evaluation included (1) a Stand Walk Sit Test during a monopolar survey of each electrode in the on-drug condition; (2) a 5-condition test with the following conditions: off-drug/off-DBS, off-drug/on-best-compromise-DBS, on-drug/off-DBS, on-drug/on-best-compromise-DBS, and on-drug/on-worsening-DBS, which utilized the contact inducing the most prominent gait deterioration. The following scales were performed: UPDRSIII subscores, Stand Walk Sit Test, and dyskinesia and freezing of gait scales. Localization of contacts was performed using a coregistration method. Twelve of 17 patients underwent the complete evaluation. Stimulation of the most proximal contacts significantly slowed down the Stand Walk Sit Test. The on-drug/on-worsening-DBS condition compared with the on-drug/off-DBS condition worsened akinesia (P = 0.02), Stand Walk Sit Test (P = 0.001), freezing of gait (P = 0.02), and improved dyskinesias (P = 0.003). Compared with the off-drug/off-DBS condition, the on-drug/on-worsening-DBS condition improved rigidity (P = 0.007) and tremor (P = 0.007). Worsening contact sites were predominantly dorsal and anterior to the STN in the anterior zona incerta and Forel fields H2. A paradoxical deterioration of gait and akinesia is a rare side effect following STN-DBS. We propose that this may be related to misplaced contacts, and we discuss the pathophysiology and strategies to identify and manage this complication. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

PubMed

Brodsky, Matthew A; Anderson, Shannon; Murchison, Charles; Seier, Mara; Wilhelm, Jennifer; Vederman, Aaron; Burchiel, Kim J

2017-11-07

To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index ( p = 0.004) and subscores for cognition ( p = 0.011) and communication ( p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points ( p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. NCT01703598. This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months. © 2017 American Academy of Neurology.

HIV-1 viral load measurement in venous blood and fingerprick blood using Abbott RealTime HIV-1 DBS assay.

PubMed

Tang, Ning; Pahalawatta, Vihanga; Frank, Andrea; Bagley, Zowie; Viana, Raquel; Lampinen, John; Leckie, Gregor; Huang, Shihai; Abravaya, Klara; Wallis, Carole L

2017-07-01

HIV RNA suppression is a key indicator for monitoring success of antiretroviral therapy. From a logistical perspective, viral load (VL) testing using Dried Blood Spots (DBS) is a promising alternative to plasma based VL testing in resource-limited settings. To evaluate the analytical and clinical performance of the Abbott RealTime HIV-1 assay using a fully automated one-spot DBS sample protocol. Limit of detection (LOD), linearity, lower limit of quantitation (LLQ), upper limit of quantitation (ULQ), and precision were determined using serial dilutions of HIV-1 Virology Quality Assurance stock (VQA Rush University), or HIV-1-containing armored RNA, made in venous blood. To evaluate correlation, bias, and agreement, 497 HIV-1 positive adult clinical samples were collected from Ivory Coast, Uganda and South Africa. For each HIV-1 participant, DBS-fingerprick, DBS-venous and plasma sample results were compared. Correlation and bias values were obtained. The sensitivity and specificity were analyzed at a threshold of 1000 HIV-1 copies/mL generated using the standard plasma protocol. The Abbott HIV-1 DBS protocol had an LOD of 839 copies/mL, a linear range from 500 to 1×10 7 copies/mL, an LLQ of 839 copies/mL, a ULQ of 1×10 7 copies/mL, and an inter-assay SD of ≤0.30 log copies/mL for all tested levels within this range. With clinical samples, the correlation coefficient (r value) was 0.896 between DBS-fingerprick and plasma and 0.901 between DBS-venous and plasma, and the bias was -0.07 log copies/mL between DBS-fingerprick and plasma and -0.02 log copies/mL between DBS-venous and plasma. The sensitivity of DBS-fingerprick and DBS-venous was 93%, while the specificity of both DBS methods was 95%. The results demonstrated that the Abbott RealTime HIV-1 assay with DBS sample protocol is highly sensitive, specific and precise across a wide dynamic range and correlates well with plasma values. The Abbott RealTime HIV-1 assay with DBS sample protocol provides an alternative sample collection and transfer option in resource-limited settings and expands the utility of a viral load test to monitor HIV-1 ART treatment for infected patients. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.

PubMed

Heldmann, Marcus; Berding, Georg; Voges, Jürgen; Bogerts, Bernhard; Galazky, Imke; Müller, Ulf; Baillot, Gunther; Heinze, Hans-Jochen; Münte, Thomas F

2012-01-01

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H(2)[(15)O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control.

Investigation of DBS electro-oxidation reaction in the aqueous-organic solution of LiClO4.

PubMed

Darlewski, Witold; Popiel, Stanisław; Nalepa, Tomasz; Gromotowicz, Waldemar; Szewczyk, Rafał; Stankiewicz, Romuald

2010-03-15

A process of dibutyl sulphide (DBS) electro-oxidation using electrolysis and cyclic voltamperometry was investigated in water-methanol solution using different electrodes (platinum, boron doped diamond, graphite and glassy carbon). Obtained results indicate that the DBS electro-oxidation process is irreversible in voltamperometric conditions. It was shown that during DBS electrolytic oxidation on Pt, at the low anode potential (1.8 V), DBS was oxidized to sulphoxide and sulphone. Electrolysis at higher potential (up to 3.0 V) resulted in complete DBS oxidation and formation of various products, including: butyric acid, sulphuric acid, butanesulphinic acid, butanesulphonic acid, identified using gas chromatography (GC-AED) and mass spectrometry (GC-MS) methods. (c) 2009 Elsevier B.V. All rights reserved.

The effect of deep brain stimulation of the subthalamic nucleus on executive functions: impaired verbal fluency and intact updating, planning and conflict resolution in Parkinson's disease.

PubMed

Demeter, Gyula; Valálik, István; Pajkossy, Péter; Szőllősi, Ágnes; Lukács, Ágnes; Kemény, Ferenc; Racsmány, Mihály

2017-04-24

Although the improvement of motor symptoms in Parkinson's disease (PD) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) is well documented, there are open questions regarding its impact on cognitive functions. The aim of this study was to assess the effect of bilateral DBS of the STN on executive functions in PD patients using a DBS wait-listed PD control group. Ten PD patients with DBS implantation (DBS group) and ten PD wait-listed patients (Clinical control group) participated in the study. Neuropsychological tasks were used to assess general mental ability and various executive functions. Each task was administered twice to each participant: before and after surgery (with the stimulators on) in the DBS group and with a matched delay between the two task administration points in the control group. There was no significant difference between the DBS and the control groups' performance in tasks measuring the updating of verbal, spatial or visual information (Digit span, Corsi and N-back tasks), planning and shifting (Trail Making B), and conflict resolution (Stroop task). However, the DBS group showed a significant decline on the semantic verbal fluency task after surgery compared to the control group, which is in line with findings of previous studies. Our results provide support for the relative cognitive safety of the STN DBS using a wait-listed PD control group. Differential effects of the STN DBS on frontostriatal networks are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Surgical Neuroanatomy and Programming in Deep Brain Stimulation for Obsessive Compulsive Disorder

PubMed Central

Morishita, Takashi; Fayad, Sarah M.; Goodman, Wayne K.; Foote, Kelly D.; Chen, Dennis; Peace, David A.; Rhoton, Albert L.; Okun, Michael S.

2014-01-01

Objectives Deep brain stimulation (DBS) has been established as a safe, effective therapy for movement disorders (Parkinson’s disease, essential tremor, etc.), and its application is expanding to the treatment of other intractable neuropsychiatric disorders including Depression and Obsessive-Compulsive Disorder (OCD). Several published studies have supported the efficacy of DBS for severely debilitating OCD. However, questions remain regarding the optimal anatomical target and the lack of a bedside programming paradigm for OCD DBS. Management of OCD DBS can be highly variable and is typically guided by each center’s individual expertise. In this paper, we review the various approaches to targeting and programming for OCD DBS. We also review the clinical experience for each proposed target, and discuss the relevant neuroanatomy. Methods A PubMed review was performed searching for literature on OCD DBS and included all articles published before March 2012. We included all available studies with a clear description of the anatomical targets, programming details, and the outcomes. Results Six different DBS approaches were identified. High frequency stimulation with high voltage was applied in most cases, and predictive factors for favorable outcomes were discussed in the literature. Conclusion DBS remains an experimental treatment for medication refractory OCD. Target selection and programming paradigms are not yet standardized, though, an improved understanding of the relationship between the DBS lead and the surrounding neuroanatomical structures will aid in the selection of targets and the approach to programming. We propose to form a registry to track OCD DBS cases for future clinical study design. PMID:24345303

Hemoglobin Adducts of Benzene Oxide in Neonatal and Adult Dried Blood Spots

PubMed Central

Funk, William E.; Waidyanatha, Suramya; Chaing, Shu H.; Rappaport, Stephen M.

2010-01-01

Adducts of reactive chemicals with hemoglobin (Hb) or human serum albumin can be used as biomarkers of internal doses of carcinogens. Since dried blood spots (DBS) are easier to collect and store than conventional venous blood samples, they encourage applications of biomarkers of exposure in large epidemiology studies. Also, neonatal DBS can be used to investigate chemical exposures in utero. Here, we report a simple method to isolate Hb from DBS with high recovery and purity using the addition of ethanol to aqueous DBS extracts. To prove the concept that DBS-derived proteins can be used to assay for adducts, we measured Hb adducts of benzene oxide, a reactive metabolite of the ubiquitous air pollutant, benzene, in 9 neonatal and 9 adult DBS (from volunteer subjects), using a gas chromatography-mass spectrometry method that we had previously developed. For comparison, benzene oxide-Hb adducts (BO-Hb) were measured in the same 9 adult subjects, using Hb that had been isolated and purified using our conventional method for venous blood. The geometric mean BO-Hb levels in all DBS samples ranged from 27.7 to 33.1 pmol/g globin. Neither of the comparisons of mean (logged) BO-Hb levels between sources (adult conventional vs. adult DBS and adult DBS vs. newborn DBS) showed a significant difference. Based upon the estimated variance of the BO-Hb levels, we had 80% power to detect a 1.7-fold difference in geometric mean levels of BO-Hb in our samples of 9 subjects. PMID:18708378

Surgical neuroanatomy and programming in deep brain stimulation for obsessive compulsive disorder.

PubMed

Morishita, Takashi; Fayad, Sarah M; Goodman, Wayne K; Foote, Kelly D; Chen, Dennis; Peace, David A; Rhoton, Albert L; Okun, Michael S

2014-06-01

Deep brain stimulation (DBS) has been established as a safe, effective therapy for movement disorders (Parkinson's disease, essential tremor, etc.), and its application is expanding to the treatment of other intractable neuropsychiatric disorders including depression and obsessive-compulsive disorder (OCD). Several published studies have supported the efficacy of DBS for severely debilitating OCD. However, questions remain regarding the optimal anatomic target and the lack of a bedside programming paradigm for OCD DBS. Management of OCD DBS can be highly variable and is typically guided by each center's individual expertise. In this paper, we review the various approaches to targeting and programming for OCD DBS. We also review the clinical experience for each proposed target and discuss the relevant neuroanatomy. A PubMed review was performed searching for literature on OCD DBS and included all articles published before March 2012. We included all available studies with a clear description of the anatomic targets, programming details, and the outcomes. Six different DBS approaches were identified. High-frequency stimulation with high voltage was applied in most cases, and predictive factors for favorable outcomes were discussed in the literature. DBS remains an experimental treatment for medication refractory OCD. Target selection and programming paradigms are not yet standardized, though an improved understanding of the relationship between the DBS lead and the surrounding neuroanatomic structures will aid in the selection of targets and the approach to programming. We propose to form a registry to track OCD DBS cases for future clinical study design. © 2013 International Neuromodulation Society.

Performance and Storage Integrity of Dried Blood Spots for PCB, BFR and Pesticide Measurements

PubMed Central

Batterman, Stuart; Chernyak, Sergei

2014-01-01

Dried blood spots (DBS) can provide accurate and valuable estimates of exposure to environmental toxicants, and the use of information derived from archived newborn DBS information has enormous potential to open up new research on the impacts of early chemical exposure on disease. Broad application of DBS for the purpose of quantitative exposure estimation requires robust and validated methods. This study investigates the suitability of DBS analyses for population studies of exposure to three chemical groups: polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), and chlorinated pesticides. It examines background (matrix) contamination, recovery and extraction variability, sensitivity, and storage stability. DBS samples prepared using 50 μL of adult blood were analyzed by GC/MS, and method performance was confirmed by using certified materials and paired DBS-blood samples from six volunteers. Several of the target compounds and their degradation products have not been previously measured in DBS. All target compounds were detected in DBS samples collected from the volunteers. Sample DBS cards showed background contamination of several compounds. When stored at room temperature, target compounds, excluding PBDEs, were stable for up to one month. When refrigerated or frozen, stability was acceptable for all compounds up to one year, and multiyear storage appears acceptable at colder (e.g., −80 °C) temperatures. Multicompartment models may be used to estimate or correct for storage losses. Considering concentrations of contaminants for adults and children reported in the literature, and experimental values of detection limits and background contamination, DBS samples are suitable for quantifying exposures to many PCBs, BFRs and persistent pesticides. PMID:25058892

Deep Brain Stimulation of the Internal Globus Pallidus Improves Response Initiation and Proactive Inhibition in Patients With Parkinson’s Disease

PubMed Central

Pan, Yixin; Wang, Linbin; Zhang, Yingying; Zhang, Chencheng; Qiu, Xian; Tan, Yuyan; Zhou, Haiyan; Sun, Bomin; Li, Dianyou

2018-01-01

Background: Impulse control disorder is not uncommon in patients with Parkinson’s disease (PD) who are treated with dopamine replacement therapy and subthalamic deep brain stimulation (DBS). Internal globus pallidus (GPi)-DBS is increasingly used, but its role in inhibitory control has rarely been explored. In this study, we evaluated the effect of GPi-DBS on inhibitory control in PD patients. Methods: A stop-signal paradigm was used to test response initiation, proactive inhibition, and reactive inhibition. The subjects enrolled in the experiment were 27 patients with PD, of whom 13 had received only drug treatment and 14 had received bilateral GPi-DBS in addition to conventional medical treatment and 15 healthy individuals. Results: Our results revealed that with GPi-DBS on, patients with PD showed significantly faster responses than the other groups in trials where it was certain that no stop signal would be presented. Proactive inhibition was significantly different in the surgical patients with GPi-DBS on versus when GPi-DBS was off, in surgical patients with GPi-DBS on versus drug-treated patients, and in healthy controls versus drug-treated patients. Correlation analyses revealed that when GPi-DBS was on, there was a statistically significant moderate positive relationship between proactive inhibition and dopaminergic medication. Conclusion: GPi-DBS may lead to an increase in response initiation speed and improve the dysfunctional proactive inhibitory control observed in PD patients. Our results may help us to understand the role of the GPi in cortical-basal ganglia circuits. PMID:29681869

The impact of pallidal and subthalamic deep brain stimulation on urologic function in Parkinson’s disease

PubMed Central

Mock, Stephen; Osborn, David J.; Brown, Elizabeth T.; Reynolds, W. Stuart; Turchan, Maxim; Pallavaram, Srivatsan; Rodriguez, William; Dmochowski, Roger; Tolleson, Christopher M.

2016-01-01

Objective Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention for treating Parkinson’s disease (PD) motor symptoms. Both surgical targets, the globus pallidus interna (GPi) and subthalamic nucleus (STN), appear equally beneficial when treating motor symptoms but effects on nonmotor symptoms are not clear. Lower urinary tract symptoms (LUTS) are a common PD complaint. Given prior data in STN-DBS, we aimed to further explore potential benefits in LUTS in both targets. Methods We performed a prospective, non-blinded clinical trial evaluating LUTS in PD patients in both targets pre and post DBS using validated urologic surveys. Participants were already slated for DBS and target selection predetermined before study entry. LUTS was evaluated using: the American Urological Association (AUA-SI), Quality of Life score (QOL), Overactive bladder 8 questionnaire (OAB-q), and sexual health inventory for men (SHIM). Results Of 33 participants, 20 underwent STN DBS and 13 had GPi DBS. Patients demonstrated moderate baseline LUTS. The urologic QOL score significantly improved post DBS (3.24±1.77vs 2.52±1.30; p=0.03). Analyzed by target, only the STN showed significant change in QOL (vs. 2.25±1.33; p=0.04). There were no other significant differences in urologic scores post DBS noted in either target. Conclusion In PD patients with moderate LUTS, there were notable improvements in QOL for LUTS post DBS in the total sample and STN target. There may be differences in DBS effects on LUTS between targets but this will require further larger, blinded studies. PMID:27172446

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

PubMed

Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L; Wang, Lily L; Zibetti, Maurizio; Duker, Andrew P; Mandybur, George T; Lopiano, Leonardo; Merola, Aristide

2018-03-06

In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

Speed effects of deep brain stimulation for Parkinson's disease.

PubMed

Klostermann, Fabian; Wahl, Michael; Marzinzik, Frank; Vesper, Jan; Sommer, Werner; Curio, Gabriel

2010-12-15

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) accelerates reaction time (RT) in patients with Parkinson's disease (PD), particularly in tasks in which decisions on the response side have to be made. This might indicate that DBS speeds up both motor and nonmotor operations. Therefore, we studied the extent to which modifications of different processing streams could explain changes of RT under subthalamic DBS. Ten PD patients on-DBS and off-DBS and 10 healthy subjects performed a choice-response task (CRT), requiring either right or left finger button presses. At the same time, EEG recordings were performed, so that RTs could be assessed together with lateralized readiness potentials (LRP), indicative of movement preparation. Additionally, an oddball task (OT) was run, in which right finger responses to target stimuli were recorded along with cognitive P300 responses. Generally, PD patients off-DBS had longer RTs than controls. Subthalamic DBS accelerated RT only in CRT. This could largely be explained by analog shortenings of LRP. No DBS-dependent changes were identified in OT, neither on the level of RT nor on the level of P300 latencies. It follows that RT accelerations under DBS of the STN are predominantly due to effects on the timing of motor instead of nonmotor processes. This starting point explains why DBS gains of response speed are low in tasks in which reactions are initiated from an advanced level of movement preparation (as in OT), and high whenever motor responses have to be raised from scratch (as in CRT). © 2010 Movement Disorder Society.

Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder

PubMed Central

de Koning, P P; Figee, M; Endert, E; van den Munckhof, P; Schuurman, P R; Storosum, J G; Denys, D; Fliers, E

2016-01-01

Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus–pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS. PMID:26812043

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

PubMed

Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C

2017-01-01

Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

Experimental and theoretical characterization of the voltage distribution generated by deep brain stimulation.

PubMed

Miocinovic, Svjetlana; Lempka, Scott F; Russo, Gary S; Maks, Christopher B; Butson, Christopher R; Sakaie, Ken E; Vitek, Jerrold L; McIntyre, Cameron C

2009-03-01

Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease and shows great promise for numerous other disorders. While the fundamental purpose of DBS is to modulate neural activity with electric fields, little is known about the actual voltage distribution generated in the brain by DBS electrodes and as a result it is difficult to accurately predict which brain areas are directly affected by the stimulation. The goal of this study was to characterize the spatial and temporal characteristics of the voltage distribution generated by DBS electrodes. We experimentally recorded voltages around active DBS electrodes in either a saline bath or implanted in the brain of a non-human primate. Recordings were made during voltage-controlled and current-controlled stimulation. The experimental findings were compared to volume conductor electric field models of DBS parameterized to match the different experiments. Three factors directly affected the experimental and theoretical voltage measurements: 1) DBS electrode impedance, primarily dictated by a voltage drop at the electrode-electrolyte interface and the conductivity of the tissue medium, 2) capacitive modulation of the stimulus waveform, and 3) inhomogeneity and anisotropy of the tissue medium. While the voltage distribution does not directly predict the neural response to DBS, the results of this study do provide foundational building blocks for understanding the electrical parameters of DBS and characterizing its effects on the nervous system.

Evaluation of dried blood spot as an alternative sample collection method for hepatitis C virus RNA quantitation and genotyping using a commercial system.

PubMed

Mahajan, Supriya; Choudhary, Manish Chandra; Kumar, Guresh; Gupta, Ekta

2018-06-01

Dried blood spot (DBS) is a minimally invasive sampling method suitable for sample collection, storage and transportation in resource limited areas. Aim of this study was to compare the diagnostic utility of DBS with plasma sample for HCV RNA quantitation and genotyping using commercial systems. Plasma and DBS card spotted samples were collected from 95 HCV seropositive patients. Both types of samples were subjected to HCV RNA by real-time PCR (Abbott m2000rt, USA). Genotyping was performed using Abbott HCV genotype II kit (Abbott diagnostics, USA) in samples with viral load > 3 log 10  IU/ml. In both plasma and DBS, 14 (14.7%) samples were negative and 81 (85.3%) were positive for HCV RNA. Median viral load in plasma (3.78; range 0-7.43) log 10  IU/ml was comparable to DBS (3.93; range 0-7.24) log 10  IU/ml. DBS demonstrated sensitivity and specificity of 97.5 and 85.7% respectively, with positive predictive value (PPV) of 97.5% and negative predictive value (NPV) of 85.7%. DBS showed good correlation (r 2  = 0.866) and agreement (93.5%) with plasma. Genotyping in 20 patients showed 100% concordance between DBS and plasma samples. DBS showed good sensitivity and specificity as a sampling method for HCV RNA quantitation and genotyping.

Dried Blood Spots - Preparing and Processing for Use in Immunoassays and in Molecular Techniques

PubMed Central

Grüner, Nico; Stambouli, Oumaima; Ross, R. Stefan

2015-01-01

The idea of collecting blood on a paper card and subsequently using the dried blood spots (DBS) for diagnostic purposes originated a century ago. Since then, DBS testing for decades has remained predominantly focused on the diagnosis of infectious diseases especially in resource-limited settings or the systematic screening of newborns for inherited metabolic disorders and only recently have a variety of new and innovative DBS applications begun to emerge. For many years, pre-analytical variables were only inappropriately considered in the field of DBS testing and even today, with the exception of newborn screening, the entire pre-analytical phase, which comprises the preparation and processing of DBS for their final analysis has not been standardized. Given this background, a comprehensive step-by-step protocol, which covers al the essential phases, is proposed, i.e., collection of blood; preparation of blood spots; drying of blood spots; storage and transportation of DBS; elution of DBS, and finally analyses of DBS eluates. The effectiveness of this protocol was first evaluated with 1,762 coupled serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections on an automated analytical platform. In a second step, the protocol was utilized during a pilot study, which was conducted on active drug users in the German cities of Berlin and Essen. PMID:25867233

Me, Myself and My Brain Implant: Deep Brain Stimulation Raises Questions of Personal Authenticity and Alienation.

PubMed

Kraemer, Felicitas

2013-01-01

In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in terms of these concepts raises new issues for not only the philosophical discussion of neuro-ethics of DBS, but also for the psychological and medical approach to patients under DBS. In particular, I suggest that the experience of alienation and authenticity varies from patient to patient with DBS. For some, alienation can be brought about by neurointerventions because patients no longer feel like themselves. But, on the other hand, it seems alienation can also be cured by DBS as other patients experience their state of mind as authentic under treatment and retrospectively regard their former lives without stimulation as alienated. I argue that we must do further research on the relevance of authenticity and alienation to patients treated with DBS in order to gain a deeper philosophical understanding, and to develop the best evaluative criterion for the behavior of DBS patients.

Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects.

PubMed

Voon, Valerie; Droux, Fabien; Chabardes, Stephan; Bougerol, Thierry; Kohl, Sina; David, Olivier; Krack, Paul; Polosan, Mircea

2018-07-01

Our daily decisions involve an element of risk, a behavioral process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus (STN) in obsessive compulsive disorder (OCD) testing on and off deep-brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. STN DBS decreased risk taking to rewards (p = 0.02) and greater risk taking to rewards was positively correlated with OCD severity (p = 0.01) and disease duration (p = 0.01). STN DBS was also associated with impaired subjective discrimination of loss magnitude (p < 0.05), an effect mediated by acute DBS rather than chronic DBS. We highlight a role for the STN in mediating dissociable valence prospects on risk seeking. STN stimulation decreases risk taking to rewards and impairs discrimination of loss magnitude. These findings may have implications for behavioral symptoms related to STN DBS and the potential for STN DBS for the treatment of psychiatric disorders. Copyright © 2018. Published by Elsevier Ltd.

The effect of preparation, storage and shipping of dried blood spots on the activity of five lysosomal enzymes.

PubMed

Elbin, Carole S; Olivova, Petra; Marashio, Carla A; Cooper, Samantha K; Cullen, Emmaline; Keutzer, Joan M; Zhang, X Kate

2011-06-11

Fluorometric and tandem mass spectrometry assays can be used to measure lysosomal enzyme activities in dried blood spots (DBS). The effect of DBS preparation, storage and shipping was evaluated on the activities of acid α-glucosidase, acid α-galactosidase, acid β-glucocerebrosidase, acid sphingomyelinase, and galactocerebrosidase. Whole blood from normal donors was used to prepare DBS following Clinical and Laboratory Standards Institute guidelines and by several deviations. Some DBS were subjected to various treatments, storage and shipping conditions. The activity of 5 lysosomal enzymes (GAA, GLA, GBA, ASM, and GALC) was measured using tandem mass spectrometric and fluorometric (GAA only) assays with 2 distinct and commonly used synthetic substrates. Enzyme activities were strongly affected by the way DBS were prepared and stored. Exposure of DBS to elevated heat and humidity can destroy enzyme functions rapidly. DBS prepared from poorly mixed blood caused significant variation on enzyme activities. EDTA, but not heparin, as an anti-coagulant gave more precise results. The study confirmed the importance of proper and consistent DBS preparation and storage when screening for deficiencies of lysosomal enzymes. Copyright © 2011 Elsevier B.V. All rights reserved.

Stimulation of the Rat Subthalamic Nucleus is Neuroprotective Following Significant Nigral Dopamine Neuron Loss

PubMed Central

Spieles-Engemann, A. L.; Behbehani, M. M.; Collier, T. J.; Wohlgenant, S. L.; Steece-Collier, K.; Paumier, K.; Daley, B. F.; Gombash, S.; Madhavan, L.; Mandybur, G. T.; Lipton, J.W.; Terpstra, B.T.; Sortwell, C.E.

2010-01-01

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson’s disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between two and four weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief. PMID:20307668

Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity

PubMed Central

Pohodich, Amy E; Yalamanchili, Hari; Raman, Ayush T; Wan, Ying-Wooi; Gundry, Michael; Hao, Shuang; Jin, Haijing; Tang, Jianrong; Liu, Zhandong

2018-01-01

Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for improvement of memory in Alzheimer’s patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder caused by loss-of-function mutations in MECP2. The mechanism of DBS benefits has been elusive, however, so we assessed changes in gene expression, splice isoforms, DNA methylation, and proteome following acute forniceal DBS in wild-type mice and mice lacking Mecp2. We found that DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis and normalized expression of ~25% of the genes altered in Mecp2-null mice. Moreover, DBS induced expression of 17–24% of the genes downregulated in other intellectual disability mouse models and in post-mortem human brain tissue from patients with Major Depressive Disorder, suggesting forniceal DBS could benefit individuals with a variety of neuropsychiatric disorders. PMID:29570050

State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

PubMed

Wagle Shukla, Aparna; Okun, Michael S

2016-01-01

Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

Catatonia after deep brain stimulation successfully treated with lorazepam and right unilateral electroconvulsive therapy: a case report.

PubMed

Quinn, Davin K; Rees, Caleb; Brodsky, Aaron; Deligtisch, Amanda; Evans, Daniel; Khafaja, Mohamad; Abbott, Christopher C

2014-09-01

The presence of a deep brain stimulator (DBS) in a patient who develops neuropsychiatric symptoms poses unique diagnostic challenges and questions for the treating psychiatrist. Catatonia has been described only once, during DBS implantation, but has not been reported in a successfully implanted DBS patient. We present a case of a patient with bipolar disorder and renal transplant who developed catatonia after DBS for essential tremor. The patient was successfully treated for catatonia with lorazepam and electroconvulsive therapy after careful diagnostic workup. Electroconvulsive therapy has been successfully used with DBS in a handful of cases, and certain precautions may help reduce potential risk. Catatonia is a rare occurrence after DBS but when present may be safely treated with standard therapies such as lorazepam and electroconvulsive therapy.

Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving Antiretroviral Therapy in Africa and Asia

PubMed Central

Monleau, Marjorie; Eymard-Duvernay, Sabrina; Dagnra, Anoumou; Kania, Dramane; Ngo-Giang-Huong, Nicole; Touré-Kane, Coumba; Truong, Lien X. T.; Chaix, Marie-Laure; Delaporte, Eric; Ayouba, Ahidjo; Peeters, Martine

2014-01-01

Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at −20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance should be monitored. PMID:24478491

Evaluation of dry blood spot technique for quantification of an Anti-CD20 monoclonal antibody drug in human blood samples.

PubMed

Lin, Yong-Qing; Zhang, Yilu; Li, Connie; Li, Louis; Zhang, Kelley; Li, Shawn

2012-01-01

To evaluate the dried blood spot (DBS) technique in ELISA quantification of larger biomolecular drugs, an anti-CD20 monoclonal antibody drug was used as an example. A method for the quantification of the anti-CD20 drug in human DBS was developed and validated. The drug standard and quality control samples prepared in fresh human blood were spotted on DBS cards and then extracted. A luminescent ELISA was used for quantification of the drug from DBS samples. The assay range of the anti-CD20 drug standards in DBS was 100-2500ng/mL. The intra-assay precision (%CV) ranged from 0.4% to 10.1%, and the accuracy (%Recovery) ranged from 77.9% to 113.9%. The inter assay precision (%CV) ranged from 5.9% to 17.4%, and the accuracy ranged from 81.5% to 110.5%. The DBS samples diluted 500 and 50-fold yielded recovery of 88.7% and 90.7%, respectively. The preparation of DBS in higher and lower hematocrit (53% and 35%) conditions did not affect the recovery of the drug. Furthermore, the storage stability of the anti-CD20 drug on DBS cards was tested at various conditions. It was found that the anti-CD20 drug was stable for one week in DBS stored at room temperature. However, it was determined that the stability was compro]mised in DBS stored at high humidity, high temperature (55°C), and exposed to direct daylight for a week, as well as for samples stored at room temperature and high humidity conditions for a month. Stability did not change significantly in samples that underwent 3 freeze/thaw cycles. Our results demonstrated a successful use of DBS technique in ELISA quantification of an anti-CD20 monoclonal antibody drug in human blood. The stability data provides information regarding sample storage and shipping for future clinical studies. It is, therefore, concluded that the DBS technique is applicable in the quantification of other large biomolecule drugs or biomarkers. Copyright © 2011 Elsevier Inc. All rights reserved.

The combined effect of subthalamic nuclei deep brain stimulation and L-dopa increases emotion recognition in Parkinson's disease.

PubMed

Mondillon, Laurie; Mermillod, Martial; Musca, Serban C; Rieu, Isabelle; Vidal, Tiphaine; Chambres, Patrick; Auxiette, Catherine; Dalens, Hélène; Marie Coulangeon, Louise; Jalenques, Isabelle; Lemaire, Jean-Jacques; Ulla, Miguel; Derost, Philippe; Marques, Ana; Durif, Franck

2012-10-01

Deep brain stimulation of the subthalamic nucleus (DBS) is a widely used surgical technique to suppress motor symptoms in Parkinson's disease (PD), and as such improves patients' quality of life. However, DBS may produce emotional disorders such as a reduced ability to recognize emotional facial expressions (EFE). Previous studies have not considered the fact that DBS and l-dopa medication can have differential, common, or complementary consequences on EFE processing. A thorough way of investigating the effect of DBS and l-dopa medication in greater detail is to compare patients' performances after surgery, with the two therapies either being administered ('on') or not administered ('off'). We therefore used a four-condition (l-dopa 'on'/DBS 'on', l-dopa 'on'/DBS 'off', l-dopa 'off'/DBS 'on', and l-dopa 'off'/DBS 'off') EFE recognition paradigm and compared implanted PD patients to healthy controls. The results confirmed those of previous studies, yielding a significant impairment in the detection of some facial expressions relative to controls. Disgust recognition was impaired when patients were 'off' l-dopa and 'on' DBS, and fear recognition impaired when 'off' of both therapies. More interestingly, the combined effect of both DBS and l-dopa administration seems much more beneficial for EFE recognition than the separate administration of each individual therapy. We discuss the implications of these findings in the light of the inverted U curve function that describes the differential effects of dopamine level on the right orbitofrontal cortex (OFC). We propose that, while l-dopa could "overdose" in dopamine the ventral stream of the OFC, DBS would compensate for this over-activation by decreasing OFC activity, thereby restoring the necessary OFC-amygdala interaction. Another finding is that, when collapsing over all treatment conditions, PD patients recognized more neutral faces than the matched controls, a result that concurs with embodiment theories. Copyright © 2012 Elsevier Ltd. All rights reserved.

Central thalamic deep brain stimulation to promote recovery from chronic posttraumatic minimally conscious state: challenges and opportunities.

PubMed

Giacino, Joseph; Fins, Joseph J; Machado, Andre; Schiff, Nicholas D

2012-07-01

Central thalamic deep brain stimulation (CT-DBS) may have therapeutic potential to improve behavioral functioning in patients with severe traumatic brain injury (TBI), but its use remains experimental. Current research suggests that the central thalamus plays a critical role in modulating arousal during tasks requiring sustained attention, working memory, and motor function. The aim of the current article is to review the methodology used in the CT-DBS protocol developed by our group, outline the challenges we encountered and offer suggestions for future DBS trials in this population. RATIONAL FOR CT-DBS IN TBI:  CT-DBS may therefore be able to stimulate these functions by eliciting action potentials that excite thalamocortical and thalamostriatal pathways. Because patients in chronic minimally conscious state (MCS) have a very low probability of regaining functional independence, yet often have significant sparing of cortical connectivity, they may represent a particularly appropriate target group for CT-DBS. PIlOT STUDY RESULTS:  We have conducted a series of single-subject studies of CT-DBS in patients with chronic posttraumatic MCS, with 24-month follow-up. Outcomes were measured using the Coma Recovery Scale-Revised as well as a battery of secondary outcome measures to capture more granular changes. Findings from our index case suggest that CT-DBS can significantly increase functional communication, motor performance, feeding, and object naming in the DBS on state, with performance in some domains remaining above baseline even after DBS was turned off. The use of CT-DBS in patients in MCS, however, presents challenges at almost every step, including during surgical planning, outcome measurement, and postoperative care. Additionally, given the difficulties of obtaining informed consent from patients in MCS and the experimental nature of the treatment, a robust, scientifically rooted ethical framework is resented for pursuing this line of work. © 2012 International Neuromodulation Society.

Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus.

PubMed

Mirski, Marek A; Ziai, Wendy C; Chiang, Jason; Hinich, Melvin; Sherman, David

2009-01-01

Anterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS. Anesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS. Latency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control. Increased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

Magnetic resonance-transcranial ultrasound fusion imaging: A novel tool for brain electrode location.

PubMed

Walter, Uwe; Müller, Jan-Uwe; Rösche, Johannes; Kirsch, Michael; Grossmann, Annette; Benecke, Reiner; Wittstock, Matthias; Wolters, Alexander

2016-03-01

A combination of preoperative magnetic resonance imaging (MRI) with real-time transcranial ultrasound, known as fusion imaging, may improve postoperative control of deep brain stimulation (DBS) electrode location. Fusion imaging, however, employs a weak magnetic field for tracking the position of the ultrasound transducer and the patient's head. Here we assessed its feasibility, safety, and clinical relevance in patients with DBS. Eighteen imaging sessions were conducted in 15 patients (7 women; aged 52.4 ± 14.4 y) with DBS of subthalamic nucleus (n = 6), globus pallidus interna (n = 5), ventro-intermediate (n = 3), or anterior (n = 1) thalamic nucleus and clinically suspected lead displacement. Minimum distance between DBS generator and magnetic field transmitter was kept at 65 cm. The pre-implantation MRI dataset was loaded into the ultrasound system for the fusion imaging examination. The DBS lead position was rated using validated criteria. Generator DBS parameters and neurological state of patients were monitored. Magnetic resonance-ultrasound fusion imaging and volume navigation were feasible in all cases and provided with real-time imaging capabilities of DBS lead and its location within the superimposed magnetic resonance images. Of 35 assessed lead locations, 30 were rated optimal, three suboptimal, and two displaced. In two cases, electrodes were re-implanted after confirming their inappropriate location on computed tomography (CT) scan. No influence of fusion imaging on clinical state of patients, or on DBS implantable pulse generator function, was found. Magnetic resonance-ultrasound real-time fusion imaging of DBS electrodes is safe with distinct precautions and improves assessment of electrode location. It may lower the need for repeated CT or MRI scans in DBS patients. © 2015 International Parkinson and Movement Disorder Society.

Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Beijnen, J H; Linn, S C

2014-07-01

The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and (Z)-endoxifen to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. Paired DBS and serum samples were obtained from 50 patients using tamoxifen and analyzed using HPLC-MS/MS. Serum concentrations were calculated from DBS concentrations using the formula calculated serum concentration = DBS concentration/([1-haematocrit (Hct)] + blood cell-to-serum ratio × Hct). The blood cell-to-serum ratio was determined ex vivo by incubating a batch of whole blood spiked with both analytes. The average Hct for female adults was imputed as a fixed value. Calculated and analyzed serum concentrations were compared using weighted Deming regression. Weighted Deming regression analysis comparing 44 matching pairs of DBS and serum samples showed a proportional bias for both analytes. Serum concentrations were calculated using [Tamoxifen] serum, calculated  = [Tamoxifen] DBS /0.779 and [(Z)-Endoxifen] serum, calculated = [(Z)-Endoxifen] DBS /0.663. Calculated serum concentrations were within 20 % of analyzed serum concentrations in 84 and 100 % of patient samples for tamoxifen and (Z)-endoxifen, respectively. In conclusion, DBS concentrations of tamoxifen and (Z)-endoxifen were equal to serum concentrations after correction for Hct and blood cell-to-serum ratio. DBS sampling can be used in clinical practice.

Deep brain stimulation of the subthalamic nucleus affects resting EEG and visual evoked potentials in Parkinson's disease.

PubMed

Jech, Robert; Růzicka, Evzen; Urgosík, Dusan; Serranová, Tereza; Volfová, Markéta; Nováková, Olga; Roth, Jan; Dusek, Petr; Mecír, Petr

2006-05-01

We studied changes of the EEG spectral power induced by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). Also analyzed were changes of visual evoked potentials (VEP) with DBS on and off. Eleven patients with advanced PD treated with bilateral DBS STN were examined after an overnight withdrawal of L-DOPA and 2 h after switching off the neurostimulators. All underwent clinical examination followed by resting EEG and VEP recordings, a procedure repeated after DBS STN was switched on. With DBS switched on, the dominant EEG frequency increased from 9.44+/-1.3 to 9.71+/-1.3 Hz (P<0.01) while its relative spectral power dropped by 11% on average (P<0.05). Switching on the neurostimulators caused a decrease in the N70/P100 amplitude of the VEP (P<0.01), which inversely correlated with the intensity of DBS (black-and-white pattern: P<0.01; color pattern: P<0.05). Despite artifacts generated by neurostimulators, the VEP and resting EEG were suitable for the detection of effects related to DBS STN. The acceleration of dominant frequency in the alpha band may be evidence of DBS STN influence on speeding up of intracortical oscillations. The spectral power decrease, seen mainly in the fronto-central region, might reflect a desynchronization in the premotor and motor circuits, though no movement was executed. Similarly, desynchronization of the cortical activity recorded posteriorly may by responsible for the VEP amplitude decrease implying DBS STN-related influence even on the visual system. Changes in idling EEG activity observed diffusely over scalp together with involvement of the VEP suggest that the effects of DBS STN reach far beyond the motor system influencing the basic mechanisms of rhythmic cortical oscillations.

Analysis of polyfluoroalkyl substances and bisphenol A in dried blood spots by liquid chromatography tandem mass spectrometry.

PubMed

Ma, Wanli; Kannan, Kurunthachalam; Wu, Qian; Bell, Erin M; Druschel, Charlotte M; Caggana, Michele; Aldous, Kenneth M

2013-05-01

Dried blood spots (DBS), collected as part of the newborn screening program (NSP) in the USA, is a valuable resource for studies on environmental chemical exposures and associated health outcomes in newborns. Nevertheless, determination of concentrations of environmental chemicals in DBS requires assays with great sensitivity, as the typical volume of blood available on a DBS with 16-mm diameter disc is approximately 50 μL. In this study, we developed a liquid-liquid extraction and high-performance liquid chromatography/tandem mass spectrometry method for the detection of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and bisphenol A (BPA) in DBS. The method was validated for accuracy, precision, and sensitivity, by spiking of target chemicals at different levels on Whatman 903 filter cards, which is used in the collection of DBS by the NSP. Contamination arising from collection, storage, and handling of DBS is an important issue to be considered in the analysis of trace levels of environmental chemicals in DBS. For the evaluation of the magnitude of background contamination, field blanks were prepared from unspotted portions of DBS filter cards collected by the NSP. The method was applied for the measurement of PFOS, PFOA, and BPA in 192 DBS specimens provided by NSP of New York State. PFOS and PFOA were detected in 100 % of the specimens analyzed. The concentrations of PFOS and PFOA measured in DBS were similar to those reported earlier in the whole blood samples of newborns. BPA was also found in 86 % of the specimens at concentrations ranging from 0.2 to 36 ng/mL (excluding two outliers). Further studies are needed to evaluate the sources of BPA exposures and health outcomes in newborns.

Deep Brain Stimulation Targeting the Fornix for Mild Alzheimer Dementia (the ADvance Trial): A Two Year Follow-up Including Results of Delayed Activation.

PubMed

Leoutsakos, Jeannie-Marie S; Yan, Haijuan; Anderson, William S; Asaad, Wael F; Baltuch, Gordon; Burke, Anna; Chakravarty, M Mallar; Drake, Kristen E; Foote, Kelly D; Fosdick, Lisa; Giacobbe, Peter; Mari, Zoltan; McAndrews, Mary Pat; Munro, Cynthia A; Oh, Esther S; Okun, Michael S; Pendergrass, Jo Cara; Ponce, Francisco A; Rosenberg, Paul B; Sabbagh, Marwan N; Salloway, Stephen; Tang-Wai, David F; Targum, Steven D; Wolk, David; Lozano, Andres M; Smith, Gwenn S; Lyketsos, Constantine G

2018-06-09

Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial). We reported safety but no clinical benefits of DBS-f versus the delayed-on (sham) treatment in 42 participants after one year. However, secondary post hoc analyses of the one-year data suggested a possible DBS-f benefit for participants≥65 years. To examine the long-term safety and clinical effects of sustained and delayed-on DBS-f treatment of mild AD after two years. 42 participants underwent implantation of DBS-f electrodes, with half randomized to active DBS-f stimulation (early on) for two years and half to delayed-on (sham) stimulation after 1 year to provide 1 year of active DBS-f stimulation (delayed on). We evaluated safety and clinical outcomes over the two years of the trial. DBS-f had a favorable safety profile with similar rates of adverse events across both trial phases (years 1 and 2) and between treatment arms. There were no differences between treatment arms on any primary clinical outcomes. However, post-hoc age group analyses suggested a possible benefit among older (>65) participants. DBS-f was safe. Additional study of mechanisms of action and methods for titrating stimulation parameters will be needed to determine if DBS has potential as an AD treatment. Future efficacy studies should focus on patients over age 65.

A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

PubMed

Park, Hae-Jeong; Park, Bumhee; Kim, Hae Yu; Oh, Maeng-Keun; Kim, Joong Il; Yoon, Misun; Lee, Jong Doo; Chang, Jin Woo

2015-05-01

As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy.

PubMed

Bergfeld, Isidoor O; Mantione, Mariska; Hoogendoorn, Mechteld L C; Horst, Ferdinand; Notten, Peter; Schuurman, P Richard; Denys, Damiaan

Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on autobiographical memories has never been established. Comparing autobiographical memories following DBS and ECT. In two hospitals in The Netherlands, we interviewed 25 TRD patients treated with DBS of the ventral anterior limb of the internal capsule (vALIC), 14 TRD patients treated with ECT and 22 healthy controls (HC) with the Autobiographical Memory Inventory - Short Form (AMI-SF) in a prospective, longitudinal study between March 2010 and August 2016. Patients treated with DBS were interviewed before surgery, after surgery, and twice during treatment over 122.7 (SD: ±22.2) weeks. Patients treated with ECT were tested before ECT, after six right unilateral (RUL) ECT sessions and twice following ECT over 65.1 (±9.3) weeks. Controls were tested four times over 81.5 (±15.6) weeks. Compared to HC, the AMI-SF score decreased faster in both TRD groups (P < 0.001). More specifically, AMI-SF score decreased in a comparable rate as HC after DBS surgery, but decreased more during treatment. The AMI-SF decrease in the ECT group was larger than both the DBS and HC groups. Both ECT and vALIC DBS result in a faster autobiographical memory decline compared to HC. DBS might have a negative impact on autobiographical memories, although less so than ECT. Future work should dissect whether DBS or characteristics of TRD cause this decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Short- and Long-Term Outcomes of Deep Brain Stimulation in Patients 70 Years and Older with Parkinson Disease.

PubMed

Mathkour, Mansour; Garces, Juanita; Scullen, Tyler; Hanna, Joshua; Valle-Giler, Edison; Kahn, Lora; Arrington, Teresa; Houghton, David; Lea, Georgia; Biro, Erin; Bui, Cuong J; Sulaiman, Olawale A R; Smith, Roger D

2017-01-01

Parkinson disease (PD) is a common neurodegenerative disease in elderly patients that may be treated with deep brain stimulation (DBS). DBS is an accepted surgical treatment in PD patients <70 years that demonstrates marked improvement in disease symptomology. Patients ≥70 years historically have been excluded from DBS therapy. Our objective is to evaluate the short- and long-term outcomes in patients with PD ≥70 years who underwent DBS at our center. In our single-center study, we retrospectively assessed a prospective registry of patients with PD treated with DBS who were ≥70 years old at the time of their procedure. Univariate analyses and 1-sample paired t test were used to evaluate data. Motor scores were evaluated with the Unified Parkinson's Disease Rating Scale III, and the effects on medication requirements were evaluated with levodopa equivalence daily doses (LEDD). Thirty-seven patients were followed for an average of 42.2 months post-DBS. The average ages at diagnosis and at the time of DBS surgery were 63.05 years and 72.45 years, respectively. Significant reductions in the average Unified Parkinson's Disease Rating Scale III score were observed (preoperative 31.8; postoperative 15.6; P < 0.0001). Significant reductions in the average LEDD (preoperative 891.94 mg; postoperative 559.6 mg; P = 0.0008) and medication doses per day (preoperative 11.54; postoperative 7.97; P = 0.0112) also were present. DBS is effective in treating elderly patients with PD. Patients experienced improvement in motor function, LEDD, and medication doses per day after DBS. Our results suggest that DBS is an effective treatment modality in elderly patients with PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Sleep-wake functions and quality of life in patients with subthalamic deep brain stimulation for Parkinson’s disease

PubMed Central

Eugster, Lukas; Oberholzer, Michael; Debove, Ines; Lachenmayer, M. Lenard; Mathis, Johannes; Pollo, Claudio; Schüpbach, W. M. Michael; Bassetti, Claudio L.

2017-01-01

Objectives Sleep-wake disturbances (SWD) are frequent in Parkinson’s disease (PD). The effect of deep brain stimulation (DBS) on SWD is poorly known. In this study we examined the subjective and objective sleep-wake profile and the quality of life (QoL) of PD patients in the context of subthalamic DBS. Patients and methods We retrospectively analyzed data from PD patients and candidates for DBS in the nucleus suthalamicus (STN). Pre-DBS, sleep-wake assessments included subjective and objective (polysomnography, vigilance tests and actigraphy) measures. Post-DBS, subjective measures were collected. QoL was assessed using the Parkinson’s Disease Questionnaire (PDQ-39) and the RAND SF-36-item Health Survey (RAND SF-36). Results Data from 74 PD patients (62% male, mean age 62.2 years, SD = 8.9) with a mean UPDRS-III (OFF) of 34.2 (SD = 14.8) and 11.8 (SD = 4.5) years under PD treatment were analyzed. Pre-DBS, daytime sleepiness, apathy, fatigue and depressive symptoms were present in 49%, 34%, 38% and 25% of patients respectively but not always as co-occurring symptoms. Sleep-wake disturbances were significantly correlated with QoL scores. One year after STN DBS, motor signs, QoL and sleepiness improved but apathy worsened. Changes in QoL were associated with changes in sleepiness and apathy but baseline sleep-wake functions were not predictive of STN DBS outcome. Conclusion In PD patients presenting for STN DBS, subjective and objective sleep-wake disturbances are common and have a negative impact on QoL before and after neurosurgery. Given the current preliminary evidence, prospective observational studies assessing subjective and objective sleep-wake variables prior to and after DBS are needed. PMID:29253029

Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle.

PubMed

Dandekar, Manoj P; Luse, Dustin; Hoffmann, Carson; Cotton, Patrick; Peery, Travis; Ruiz, Christian; Hussey, Caroline; Giridharan, Vijayasree V; Soares, Jair C; Quevedo, Joao; Fenoy, Albert J

2017-08-01

Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS. Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On. For DBS, a concentric bipolar electrode was stereotactically implanted into the right MFB. Exploratory activity and depression-like behavior were evaluated using the open-field and forced-swimming test (FST), respectively. MFB-DBS effects on the dopaminergic system were evaluated using immunoblotting for tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors (D1-D5), and high-performance liquid chromatography for quantifying dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in brain homogenates of prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc). Animals receiving MFB-DBS showed a significant increase in swimming time without alterations in locomotor activity, relative to the DBS-Off (p<0.039) and sham-operated groups (p<0.014), indicating an antidepressant-like response. MFB-DBS led to a striking increase in protein levels of dopamine D2 receptors and DAT in the PFC and hippocampus, respectively. However, we did not observe appreciable differences in the expression of other dopamine receptors, TH, or in the concentrations of dopamine, DOPAC, and HVA in PFC, hippocampus, amygdala, and NAc. This study was not performed on an animal model of TRD. MFB-DBS rescues the depression-like phenotypes and selectively activates expression of dopamine receptors in brain regions distant from the target area of stimulation. Copyright © 2017. Published by Elsevier B.V.

Validation and Application of a Dried Blood Spot Ceftriaxone Assay

PubMed Central

Page-Sharp, Madhu; Nunn, Troy; Salman, Sam; Moore, Brioni R.; Batty, Kevin T.; Davis, Timothy M. E.

2015-01-01

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic/pharmacodynamic (PK/PD) studies in situations where venous blood sampling is logistically and/or ethically problematic. In this study, we aimed to develop, validate, and apply a DBS ceftriaxone assay. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) DBS ceftriaxone assay was assessed for matrix effects, process efficiency, recovery, variability, and limits of quantification (LOQ) and detection (LOD). The effects of hematocrit, protein binding, red cell partitioning, and chad positioning were evaluated, and thermal stability was assessed. Plasma, DBS, and cell pellet ceftriaxone concentrations in 10 healthy adults were compared, and plasma concentration-time profiles of DBS and plasma ceftriaxone were incorporated into population PK models. The LOQ and LOD for ceftriaxone in DBS were 0.14 mg/liter and 0.05 mg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations (r > 0.95, P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were similar. At 35°C, 21°C, 4°C, −20°C, and −80°C, ceftriaxone retained >95% initial concentrations in DBS for 14 h, 35 h, 30 days, 21 weeks, and >11 months, respectively. The present DBS ceftriaxone assay is robust and can be used as a surrogate for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including in studies of young children and of those in remote or resource-poor settings. PMID:26438505

Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

PubMed

Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

2015-12-01

Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

SPECT and PET analysis of subthalamic stimulation in Parkinson's disease: analysis using a manual segmentation.

PubMed

Haegelen, Claire; García-Lorenzo, Daniel; Le Jeune, Florence; Péron, Julie; Gibaud, Bernard; Riffaud, Laurent; Brassier, Gilles; Barillot, Christian; Vérin, Marc; Morandi, Xavier

2010-03-01

The subthalamic nucleus (STN) has become an effective target of deep-brain stimulation (DBS) in severely disabled patients with advanced Parkinson's disease (PD). Clinical studies have reported DBS-induced adverse effects on cognitive functions, mood, emotion and behavior. STN DBS seems to interfere with the limbic functions of the basal ganglia, but the limbic effects of STN DBS are controversial. We measured prospectively resting regional cerebral metabolism (rCMb) with 18-fluorodeoxyglucose and PET, and resting regional cerebral blood flow (rCBF) with HMPAO and SPECT in six patients with Parkinson's disease. We compared PET and SPECT 1 month before and 3 months after STN DBS. On cerebral MRI, 13 regions of interest (ROI) were manually delineated slice by slice in frontal and limbic lobes. We obtained mean rCBF and rCMb values for each ROI and the whole brain. We normalized rCBF and rCMB values to ones for the whole brain volume, which we compared before and following STN DBS. No significant difference emerged in the SPECT analysis. PET analysis revealed a significant decrease in rCMb following STN DBS in the superior frontal gyri and left and right dorsolateral prefrontal cortex (p < 0.05). A non-significant decrease in rCMb in the left anterior cingulate gyrus appeared following STN DBS (p = 0.075). Our prospective SPECT and PET study revealed significantly decreased glucose metabolism of the two superior frontal gyri without any attendant perfusion changes following STN DBS. These results suggest that STN DBS may change medial prefrontal function and therefore the integration of limbic information, either by disrupting emotional processes within the STN, or by hampering the normal function of a limbic circuit.

Stimulation of subgenual cingulate area decreases limbic top-down effect on ventral visual stream: A DBS-EEG pilot study.

PubMed

Kibleur, Astrid; Polosan, Mircea; Favre, Pauline; Rudrauf, David; Bougerol, Thierry; Chabardès, Stéphan; David, Olivier

2017-02-01

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (area CG25) is beneficial in treatment resistant depression. Though the mechanisms of action of Cg25 DBS remain largely unknown, it is commonly believed that Cg25 DBS modulates limbic activity of large networks to achieve thymic regulation of patients. To investigate how emotional attention is influenced by Cg25 DBS, we assessed behavioral and electroencephalographic (EEG) responses to an emotional Stroop task in 5 patients during ON and OFF stimulation conditions. Using EEG source localization, we found that the main effect of DBS was a reduction of neuronal responses in limbic regions (temporal pole, medial prefrontal and posterior cingulate cortices) and in ventral visual areas involved in face processing. In the dynamic causal modeling (DCM) approach, the changes of the evoked response amplitudes are assumed to be due to changes of long range connectivity induced by Cg25 DBS. Here, using a simplified neural mass model that did not take explicitly into account the cytoarchitecture of the considered brain regions, we showed that the remote action of Cg25 DBS could be explained by a reduced top-down effective connectivity of the amygdalo-temporo-polar complex. Overall, our results thus indicate that Cg25 DBS during the emotional Stroop task causes a decrease of top-down limbic influence on the ventral visual stream itself, rather than a modulation of prefrontal cognitive processes only. Tuning down limbic excitability in relation to sensory processing might be one of the biological mechanisms through which Cg25 DBS produces positive clinical outcome in the treatment of resistant depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Deep brain stimulation of the ventral striatal area for poststroke pain syndrome: a magnetoencephalography study.

PubMed

Gopalakrishnan, Raghavan; Burgess, Richard C; Malone, Donald A; Lempka, Scott F; Gale, John T; Floden, Darlene P; Baker, Kenneth B; Machado, Andre G

2018-06-01

Poststroke pain syndrome (PSPS) is an often intractable disorder characterized by hemiparesis associated with unrelenting chronic pain. Although traditional analgesics have largely failed, integrative approaches targeting affective-cognitive spheres have started to show promise. Recently, we demonstrated that deep brain stimulation (DBS) of the ventral striatal area significantly improved the affective sphere of pain in patients with PSPS. In the present study, we examined whether electrophysiological correlates of pain anticipation were modulated by DBS that could serve as signatures of treatment effects. We recorded event-related fields (ERFs) of pain anticipation using magnetoencephalography (MEG) in 10 patients with PSPS preoperatively and postoperatively in DBS OFF and ON states. Simple visual cues evoked anticipation as patients awaited a painful (PS) or nonpainful stimulus (NPS) to the nonaffected or affected extremity. Preoperatively, ERFs showed no difference between PS and NPS anticipation to the affected extremity, possibly due to loss of salience in a network saturated by pain experience. DBS significantly modulated the early N1, consistent with improvements in affective networks involving restoration of salience and discrimination capacity. Additionally, DBS suppressed the posterior P2 (aberrant anticipatory anxiety) while enhancing the anterior N1 (cognitive and emotional regulation) in responders. DBS-induced changes in ERFs could potentially serve as signatures for clinical outcomes. NEW & NOTEWORTHY We examined the electrophysiological correlates of pain affect in poststroke pain patients who underwent deep brain stimulation (DBS) targeting the ventral striatal area under a randomized, controlled trial. DBS significantly modulated early event-related components, particularly N1 and P2, measured with magnetoencephalography during a pain anticipatory task, compared with baseline and the DBS-OFF condition, pointing to possible mechanisms of action. DBS-induced changes in event-related fields could potentially serve as biomarkers for clinical outcomes.

Deep brain stimulation, brain maps and personalized medicine: lessons from the human genome project.

PubMed

Fins, Joseph J; Shapiro, Zachary E

2014-01-01

Although the appellation of personalized medicine is generally attributed to advanced therapeutics in molecular medicine, deep brain stimulation (DBS) can also be so categorized. Like its medical counterpart, DBS is a highly personalized intervention that needs to be tailored to a patient's individual anatomy. And because of this, DBS like more conventional personalized medicine, can be highly specific where the object of care is an N = 1. But that is where the similarities end. Besides their differing medical and surgical provenances, these two varieties of personalized medicine have had strikingly different impacts. The molecular variant, though of a more recent vintage has thrived and is experiencing explosive growth, while DBS still struggles to find a sustainable therapeutic niche. Despite its promise, and success as a vetted treatment for drug resistant Parkinson's Disease, DBS has lagged in broadening its development, often encountering regulatory hurdles and financial barriers necessary to mount an adequate number of quality trials. In this paper we will consider why DBS-or better yet neuromodulation-has encountered these challenges and contrast this experience with the more successful advance of personalized medicine. We will suggest that personalized medicine and DBS's differential performance can be explained as a matter of timing and complexity. We believe that DBS has struggled because it has been a journey of scientific exploration conducted without a map. In contrast to molecular personalized medicine which followed the mapping of the human genome and the Human Genome Project, DBS preceded plans for the mapping of the human brain. We believe that this sequence has given personalized medicine a distinct advantage and that the fullest potential of DBS will be realized both as a cartographical or electrophysiological probe and as a modality of personalized medicine.

The Use of Dried Blood Spots for Pharmacokinetic Monitoring of Vemurafenib Treatment in Melanoma Patients.

PubMed

Nijenhuis, Cynthia M; Huitema, Alwin D R; Marchetti, Serena; Blank, Christian; Haanen, John B A G; van Thienen, Johannes V; Rosing, Hilde; Schellens, Jan H M; Beijnen, Jos H

2016-10-01

Pharmacokinetic monitoring is increasingly becoming an important part of clinical care of tyrosine kinase inhibitor treatment. Vemurafenib is an oral tyrosine kinase inhibitor that inhibits mutated serine/threonine protein kinase B-Raf (BRAF) and is approved for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. The aim of this study was to establish the relationship between dried blood spot (DBS) and plasma concentrations of vemurafenib to enable the use of DBS sampling, which is a minimally invasive form of sample collection. In total, 43 paired plasma and DBS samples (in duplicate) were obtained from 8 melanoma patients on vemurafenib therapy and were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Plasma concentrations were predicted from the DBS concentrations using 2 methods: (1) individual hematocrit correction and blood cell-to-plasma partitioning and (2) the calculated slope explaining the relationship between DBS and plasma concentrations (without individual hematocrit correction). Vemurafenib DBS concentrations and plasma concentrations showed a strong correlation (r = 0.964), and the relationship could be described by ([vemurafenib]plasma = [vemurafenib]DBS /0.64). The predicted plasma concentrations were within ±20% of the analyzed plasma concentrations in 97% and 100% of the samples for the methods with and without hematocrit correction, respectively. In conclusion, DBS concentrations and plasma concentrations of vemurafenib are highly correlated. Plasma concentrations can be predicted from DBS concentration using the blood cell-to-plasma partition and the average hematocrit value of this cohort (0.40 L/L). DBS sampling for pharmacokinetic monitoring of vemurafenib treatment can be used in clinical practice. © 2016, The American College of Clinical Pharmacology.

Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example

PubMed Central

Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F.; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C.

2017-01-01

Background Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Objective Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Methods Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson’s disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Results Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Conclusion Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation. PMID:28441410

Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals.

PubMed

Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J; Duffy, Penelope S; Abulseoud, Osama A; Marsh, Michael P; Kelsey, Katherine; Blaha, Charles D; Bennet, Kevin E; Frye, Mark A; Lee, Kendall H

2013-12-15

Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) thalamic nuclei has been considered an option for treating Tourette syndrome. Using a large animal DBS model, this study was designed to explore the network effects of CM-Pf DBS. The combination of DBS and functional magnetic resonance imaging is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. With a within-subjects design, we tested the proportional effects of CM and Pf DBS by manipulating current spread and varying stimulation contacts in healthy pigs (n = 5). Our results suggests that CM-Pf DBS has an inhibitory modulating effect in areas that have been suggested as contributing to impaired sensory-motor and emotional processing. The results also help to define the differential neural circuitry effects of the CM and Pf with evidence of prominent sensorimotor/associative effects for CM DBS and prominent limbic/associative effects for Pf DBS. Our results support the notion that stimulation of deep brain structures, such as the CM-Pf, modulates multiple networks with cortical effects. The networks affected by CM-Pf stimulation in this study reinforce the conceptualization of Tourette syndrome as a condition with psychiatric and motor symptoms and of CM-Pf DBS as a potentially effective tool for treating both types of symptoms. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of deep brain stimulation of the subthalamic nucleus on perceptual decision making.

PubMed

Zaehle, Tino; Wagenbreth, Caroline; Voges, Jürgen; Heinze, Hans-Jochen; Galazky, Imke

2017-02-20

When faced with difficult decisions, people prefer to stay with the default. This status quo bias often leads to suboptimal choice behavior. Neurophysiological evidence suggests a pivot role of the Subthalamic Nucleus (STN) for overcoming such status quo bias in difficult decisions, but causal evidence is lacking. The present study investigated whether subthalamic deep brain stimulation (DBS) in patients with Parkinson's disease (PD) influences the status quo bias. Eighteen PD patients treated with STN-DBS performed a difficult perceptual decision task incorporating intrinsic status quo option. Patients were tested with (ON) and without (OFF) active STN stimulation. Our results show that DBS of the STN affected perceptual decision making in PD patients depending on the difficulty of decision. STN-DBS improved difficult perceptual decisions due to a selective increase in accuracy (hit rate) that was independent of response bias (no effect on false alarm rate). Furthermore, STN-DBS impacted status quo bias as a function of baseline impulsivity. In impulsive patients, STN-DBS increased the default bias, whereas in less impulsive PD patients, DBS of the STN reduced the status quo bias. In line with our hypothesis, STN-DBS selectively affected the tendency to stick with the default option on difficult decisions, and promoted increased decision accuracy. Moreover, we demonstrate the impact of baseline cognitive abilities on DBS-related performance changes in PD patients. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Computational modeling of an endovascular approach to deep brain stimulation

NASA Astrophysics Data System (ADS)

Teplitzky, Benjamin A.; Connolly, Allison T.; Bajwa, Jawad A.; Johnson, Matthew D.

2014-04-01

Objective. Deep brain stimulation (DBS) therapy currently relies on a transcranial neurosurgical technique to implant one or more electrode leads into the brain parenchyma. In this study, we used computational modeling to investigate the feasibility of using an endovascular approach to target DBS therapy. Approach. Image-based anatomical reconstructions of the human brain and vasculature were used to identify 17 established and hypothesized anatomical targets of DBS, of which five were found adjacent to a vein or artery with intraluminal diameter ≥1 mm. Two of these targets, the fornix and subgenual cingulate white matter (SgCwm) tracts, were further investigated using a computational modeling framework that combined segmented volumes of the vascularized brain, finite element models of the tissue voltage during DBS, and multi-compartment axon models to predict the direct electrophysiological effects of endovascular DBS. Main results. The models showed that: (1) a ring-electrode conforming to the vessel wall was more efficient at neural activation than a guidewire design, (2) increasing the length of a ring-electrode had minimal effect on neural activation thresholds, (3) large variability in neural activation occurred with suboptimal placement of a ring-electrode along the targeted vessel, and (4) activation thresholds for the fornix and SgCwm tracts were comparable for endovascular and stereotactic DBS, though endovascular DBS was able to produce significantly larger contralateral activation for a unilateral implantation. Significance. Together, these results suggest that endovascular DBS can serve as a complementary approach to stereotactic DBS in select cases.

Recent advances in deep brain stimulation in psychiatric disorders.

PubMed

Clair, Anne-Hélène; Haynes, William; Mallet, Luc

2018-01-01

Deep brain stimulation (DBS) has been offered to patients suffering of severe and resistant neuropsychiatric disorders like Obsessive Compulsive Disorder (OCD), Gilles de la Tourette Syndrome (TS) and Major Depression (MDD). Modulation of several targets within the cortico-striato-thalamo-cortical circuits can lead to a decrease of symptom severity in those patients. This review focuses on the recent clinical outcomes in DBS in psychiatric disorders. Studies on OCD and TS are now focusing on the long-term effects of DBS, with encouraging results regarding not only the decrease of symptoms, but also quality of life. They also highlighted efficient adjuvant techniques, like cognitive and behavioural therapy and support programs, to enhance an often-partial response to DBS. The application of DBS for MDD is more recent and, despite encouraging initial open-label studies, two large randomised studies have failed to demonstrate an efficacy of DBS in MDD according to evidence-based medicine criteria. Last years, DBS was also tested in other resistant psychiatric disorders, as anorexia nervosa and addiction, with encouraging preliminary results. However, today, no target - whatever the disease - can meet the criteria for clinical efficacy as recently defined by an international committee for neurosurgery for psychiatric disorders. Consequently, DBS in psychiatric disorders still needs to proceed within the frame of clinical trials.

Quantification of multiple elements in dried blood spot samples.

PubMed

Pedersen, Lise; Andersen-Ranberg, Karen; Hollergaard, Mads; Nybo, Mads

2017-08-01

Dried blood spots (DBS) is a unique matrix that offers advantages compared to conventional blood collection making it increasingly popular in large population studies. We here describe development and validation of a method to determine multiple elements in DBS. Elements were extracted from punches and analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). The method was evaluated with quality controls with defined element concentration and blood spiked with elements to assess accuracy and imprecision. DBS element concentrations were compared with concentrations in venous blood. Samples with different hematocrit were spotted onto filter paper to assess hematocrit effect. The established method was precise and accurate for measurement of most elements in DBS. There was a significant but relatively weak correlation between measurement of the elements Mg, K, Fe, Cu, Zn, As and Se in DBS and venous whole blood. Hematocrit influenced the DBS element measurement, especially for K, Fe and Zn. Trace elements can be measured with high accuracy and low imprecision in DBS, but contribution of signal from the filter paper influences measurement of some elements present at low concentrations. Simultaneous measurement of K and Fe in DBS extracts may be used to estimate sample hematocrit. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

DBS-platform for biomonitoring and toxicokinetics of toxicants: proof of concept using LC-MS/MS analysis of fipronil and its metabolites in blood

NASA Astrophysics Data System (ADS)

Raju, Kanumuri Siva Rama; Taneja, Isha; Rashid, Mamunur; Sonkar, Ashish Kumar; Wahajuddin, Muhammad; Singh, Sheelendra Pratap

2016-03-01

A simple, sensitive and high throughput LC-MS/MS method was developed and validated for quantification of fipronil, fipronil sulfone and fipronil desulfinyl in rat and human dried blood spots (DBS). DBS samples were prepared by spiking 10 μl blood on DMPK-C cards followed by drying at room temperature. The whole blood spots were then punched from the card and extracted using acetonitrile. The total chromatographic run time of the method was only 2 min. The lower limit of quantification of the method was 0.1 ng/ml for all the analytes. The method was successfully applied to determine fipronil desulfinyl in DBS samples obtained from its toxicokinetic study in rats following intravenous dose (1 mg/kg). In conclusion, the proposed DBS methodology has significant potential in toxicokinetics and biomonitoring studies of environmental toxicants. This microvolume DBS technique will be an ideal tool for biomonitoring studies, particularly in paediatric population. Small volume requirements, minimally invasive blood sampling method, easier storage and shipping procedure make DBS a suitable technique for such studies. Further, DBS technique contributes towards the principles of 3Rs resulting in significant reduction in the number of rodents used and refinement in sample collection for toxicokinetic studies.

Reduction of influence of task difficulty on perceptual decision making by STN deep brain stimulation.

PubMed

Green, Nikos; Bogacz, Rafal; Huebl, Julius; Beyer, Ann-Kristin; Kühn, Andrea A; Heekeren, Hauke R

2013-09-09

Neurocomputational models of optimal decision making ascribe a crucial role-the computation of conflict between choice alternatives-to the subthalamic nucleus (STN). Specifically, these models predict that deep brain stimulation (DBS) of the STN will diminish the influence of decision conflict on decision making. In this work, patients with Parkinson's disease judged the direction of motion in random dot stimuli while ON and OFF DBS. To induce decision conflict, we varied the task difficulty (motion coherence), leading to increased reaction time (RT) in trials with greater task difficulty in healthy subjects. Results indicate that DBS significantly influences performance for perceptual decisions under high decision conflict. RT increased substantially OFF DBS as the task became more difficult, and a diffusion model best accounted for behavioral data. In contrast, ON DBS, the influence of task difficulty on RT was significantly reduced and a race model best accounted for the observed data. Individual data fits of evidence accumulation models demonstrate different information processing under distinct DBS states. Furthermore, ON DBS, speed-accuracy tradeoffs affected the magnitude of decision criterion adjustment significantly less compared to OFF DBS. Together, these findings suggest a crucial role for the STN in adjusting decision making during high-conflict trials in perceptual decision making. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of simultaneous MEG and intracranial LFP recordings during Deep Brain Stimulation: a protocol and experimental validation

PubMed Central

Oswal, Ashwini; Jha, Ashwani; Neal, Spencer; Reid, Alphonso; Bradbury, David; Aston, Peter; Limousin, Patricia; Foltynie, Tom; Zrinzo, Ludvic; Brown, Peter; Litvak, Vladimir

2016-01-01

Background Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required. New method In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings. Results Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS. Comparison with existing approaches To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS. PMID:26698227

Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation.

PubMed

Cukiert, Arthur; Cukiert, Cristine Mella; Argentoni-Baldochi, Meire; Baise, Carla; Forster, Cássio Roberto; Mello, Valeria Antakli; Burattini, José Augusto; Lima, Alessandra Moura

2011-12-01

Deep brain stimulation (DBS) has been used in an increasing frequency for treatment of refractory epilepsy. Acute deep brain macrostimulation intraoperative findings were sparsely published in the literature. We report on our intraoperative macrostimulation findings during thalamic and hippocampal DBS implantation. Eighteen patients were studied. All patients underwent routine pre-operative evaluation that included clinical history, neurological examination, interictal and ictal EEG, high resolution 1.5T MRI and neuropsychological testing. Six patients with temporal lobe epilepsy were submitted to hippocampal DBS (Hip-DBS); 6 patients with focal epilepsy were submitted to anterior thalamic nucleus DBS (AN-DBS) and 6 patients with generalized epilepsy were submitted to centro-median thalamic nucleus DBS (CM-DBS). Age ranged from 9 to 40 years (11 males). All patients were submitted to bilateral quadripolar DBS electrode implantation in a single procedure, under general anesthesia, and intraoperative scalp EEG monitoring. Final electrode's position was checked postoperatively using volumetric CT scanning. Bipolar stimulation using the more proximal and distal electrodes was performed. Final standard stimulation parameters were 6Hz, 4V, 300μs (low frequency range: LF) or 130Hz, 4V, 300μs (high frequency range: HF). Bilateral recruiting response (RR) was obtained after unilateral stimulation in all patients submitted to AN and CM-DBS using LF stimulation. RR was widespread but prevailed over the fronto-temporal region bilaterally, and over the stimulated hemisphere. HF stimulation led to background slowing and a DC shift. The mean voltage for the appearance of RR was 4V (CM) and 3V (AN). CM and AN-DBS did not alter inter-ictal spiking frequency or morphology. RR obtained after LF Hip-DBS was restricted to the stimulated temporal lobe and no contralateral activation was noted. HF stimulation yielded no visually recognizable EEG modification. Mean intensity for initial appearance of RR was 3V. In 5 of the 6 patients submitted to Hip-DBS, an increase in inter-ictal spiking was noted unilaterally immediately after electrode insertion. Intraoperative LF stimulation did not modify temporal lobe spiking; on the other hand, HF was effective in abolishing inter-ictal spiking in 4 of the 6 patients studied. There was no immediate morbidity or mortality in this series. Macrostimulation might be used to confirm that the hardware was working properly. There was no typical RR derived from each studied thalamic nuclei after LF stimulation. On the other hand, absence of such RRs was highly suggestive of hardware malfunction or inadequate targeting. Thalamic-DBS (Th-DBS) RR was always bilateral after unilateral stimulation, although they somehow prevailed over the stimulated hemisphere. Contrary to Th-DBS, Hip-DBS gave rise to localized RR over the ipsolateral temporal neocortex, and absence of this response might very likely be related to inadequate targeting or hardware failure. Increased spiking was seen over temporal neocortex during hippocampal electrode insertion; this might point to the more epileptogenic hippocampal region in each individual patient. We did not notice any intraoperative response difference among patients with temporal lobe epilepsy with or without MTS. The relationship between these intraoperative findings and seizure outcome is not yet clear and should be further evaluated. 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Selective left, right and bilateral stimulation of subthalamic nuclei in Parkinson's disease: differential effects on motor, speech and language function.

PubMed

Schulz, Geralyn M; Hosey, Lara A; Bradberry, Trent J; Stager, Sheila V; Lee, Li-Ching; Pawha, Rajesh; Lyons, Kelly E; Metman, Leo Verhagen; Braun, Allen R

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

Speech outcomes in Parkinson's disease after subthalamic nucleus deep brain stimulation: A systematic review.

PubMed

Aldridge, Danielle; Theodoros, Deborah; Angwin, Anthony; Vogel, Adam P

2016-12-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in reducing motor symptoms for many individuals with Parkinson's disease (PD). However, STN DBS does not appear to influence speech in the same way, and may result in a variety of negative outcomes for people with PD (PWP). A high degree of inter-individual variability amongst PWP regarding speech outcomes following STN DBS is evident in many studies. Furthermore, speech studies in PWP following STN DBS have employed a wide variety of designs and methodologies, which complicate comparison and interpretation of outcome data amongst studies within this growing body of research. An analysis of published evidence regarding speech outcomes in PWP following STN DBS, according to design and quality, is missing. This systematic review aimed to analyse and coalesce all of the current evidence reported within observational and experimental studies investigating the effects of STN DBS on speech. It will strengthen understanding of the relationship between STN DBS and speech, and inform future research by highlighting methodological limitations of current evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

DBS Programming: An Evolving Approach for Patients with Parkinson's Disease.

PubMed

Wagle Shukla, Aparna; Zeilman, Pam; Fernandez, Hubert; Bajwa, Jawad A; Mehanna, Raja

2017-01-01

Deep brain stimulation (DBS) surgery is a well-established therapy for control of motor symptoms in Parkinson's disease. Despite an appropriate targeting and an accurate placement of DBS lead, a thorough and efficient programming is critical for a successful clinical outcome. DBS programming is a time consuming and laborious manual process. The current approach involves use of general guidelines involving determination of the lead type, electrode configuration, impedance check, and battery check. However there are no validated and well-established programming protocols. In this review, we will discuss the current practice and the recent advances in DBS programming including the use of interleaving, fractionated current, directional steering of current, and the use of novel DBS pulses. These technological improvements are focused on achieving a more efficient control of clinical symptoms with the least possible side effects. Other promising advances include the introduction of computer guided programming which will likely impact the efficiency of programming for the clinicians and the possibility of remote Internet based programming which will improve access to DBS care for the patients.

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson's disease.

PubMed

Luoma, Jarkko; Pekkonen, Eero; Airaksinen, Katja; Helle, Liisa; Nurminen, Jussi; Taulu, Samu; Mäkelä, Jyrki P

2018-06-22

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD. Copyright © 2018. Published by Elsevier B.V.

DBS Programming: An Evolving Approach for Patients with Parkinson's Disease

PubMed Central

Zeilman, Pam; Fernandez, Hubert; Bajwa, Jawad A.

2017-01-01

Deep brain stimulation (DBS) surgery is a well-established therapy for control of motor symptoms in Parkinson's disease. Despite an appropriate targeting and an accurate placement of DBS lead, a thorough and efficient programming is critical for a successful clinical outcome. DBS programming is a time consuming and laborious manual process. The current approach involves use of general guidelines involving determination of the lead type, electrode configuration, impedance check, and battery check. However there are no validated and well-established programming protocols. In this review, we will discuss the current practice and the recent advances in DBS programming including the use of interleaving, fractionated current, directional steering of current, and the use of novel DBS pulses. These technological improvements are focused on achieving a more efficient control of clinical symptoms with the least possible side effects. Other promising advances include the introduction of computer guided programming which will likely impact the efficiency of programming for the clinicians and the possibility of remote Internet based programming which will improve access to DBS care for the patients. PMID:29147598

Nucleus Accumbens Deep Brain Stimulation in Patients with Substance Use Disorders and Delay Discounting.

PubMed

Peisker, Canan B; Schüller, Thomas; Peters, Jan; Wagner, Ben J; Schilbach, Leonhard; Müller, Ulf J; Visser-Vandewalle, Veerle; Kuhn, Jens

2018-01-27

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) shows first promising results in patients with severe substance use disorder (SUD), a patient group known to have deficits in self-control. One facet of self-control is the ability to forego smaller sooner rewards in favor of larger later rewards (delay discounting, DD). The NAc has been suggested to integrate motivational information to guide behavior while the consequences of NAc-DBS on DD are unknown. To this end, nine patients with SUD performed a DD task with DBS on and after a 24 h DBS off period. Furthermore, 18 healthy controls were measured to assess possible alterations in DD in patients with SUD. Our findings implicate that DD was not significantly modulated by NAc-DBS and also that patients with SUD did not differ from healthy controls. While null results must be interpreted with caution, the commonly observed association of impaired DD in SUD might suggest a long-term effect of NAc-DBS that was not sufficiently modulated by a 24 h DBS off period.

Neuroimaging and cognitive changes during déjà vu.

PubMed

Kovacs, Norbert; Auer, Tibor; Balas, Istvan; Karadi, Kazmer; Zambo, Katalin; Schwarcz, Attila; Klivenyi, Peter; Jokeit, Hennric; Horvath, Krisztina; Nagy, Ferenc; Janszky, Jozsef

2009-01-01

The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

Impulsivity and decision-making in obsessive-compulsive disorder after effective deep brain stimulation or treatment as usual.

PubMed

Grassi, Giacomo; Figee, Martijn; Ooms, Pieter; Righi, Lorenzo; Nakamae, Takashi; Pallanti, Stefano; Schuurman, Rick; Denys, Damiaan

2018-06-04

Impulsivity and impaired decision-making have been proposed as obsessive-compulsive disorder (OCD) endophenotypes, running in OCD and their healthy relatives independently of symptom severity and medication status. Deep brain stimulation (DBS) targeting the ventral limb of the internal capsule (vALIC) and the nucleus accumbens (Nacc) is an effective treatment strategy for treatment-refractory OCD. The effectiveness of vALIC-DBS for OCD has been linked to its effects on a frontostriatal network that is also implicated in reward, impulse control, and decision-making. While vALIC-DBS has been shown to restore reward dysfunction in OCD patients, little is known about the effects of vALIC-DBS on impulsivity and decision-making. The aim of the study was to compare cognitive impulsivity and decision-making between OCD patients undergoing effective vALIC-DBS or treatment as usual (TAU), and healthy controls. We used decision-making performances under ambiguity on the Iowa Gambling Task and reflection impulsivity on the Beads Task to compare 20 OCD patients effectively treated with vALIC-DBS, 40 matched OCD patients undergoing effective TAU (medication and/or cognitive behavioural therapy), and 40 healthy subjects. Effective treatment was defined as at least 35% improvement of OCD symptoms. OCD patients, irrespective of treatment modality (DBS or TAU), showed increased reflection impulsivity and impaired decision-making compared to healthy controls. No differences were observed between OCD patients treated with DBS or TAU. OCD patients effectively treated with vALIC-DBS or TAU display increased reflection impulsivity and impaired decision-making independent of the type of treatment.

Deep brain stimulation and ethics: perspectives from a multisite qualitative study of Canadian neurosurgical centers.

PubMed

Bell, Emily; Maxwell, Bruce; McAndrews, Mary Pat; Sadikot, Abbas; Racine, Eric

2011-12-01

Deep brain stimulation (DBS) is an approved neurosurgical intervention for motor disorders such as Parkinson disease. The emergence of psychiatric uses for DBS combined with the fact that it is an invasive and expensive procedure creates important ethical and social challenges in the delivery of care that need further examination. We endeavored to examine health care provider perspectives on ethical and social challenges encountered in DBS. Health care providers working in Canadian DBS surgery programs participated in a semistructured interview to identify and characterize ethical and social challenges of DBS. A content analysis of the interviews was conducted. Several key ethical issues, such as patient screening and resource allocation, were identified by members of neurosurgical teams. Providers described challenges in selecting patients for DBS on the basis of unclear evidence-based guidance regarding behavioral issues or cognitive criteria. Varied contexts of resource allocation, including some very challenging schemas, were also reported. In addition, the management of patients in the community was highlighted as a source of ethical and clinical complexity, given the need for coordinated long-term care. This study provides insights into the complexity of ethical challenges that providers face in the use of DBS across different neurosurgical centers. We propose actions for health care providers for the long-term care and postoperative monitoring of patients with DBS. More data on patient perspectives in DBS would complement the understanding of key challenges, as well as contribute to best practices, for patient selection, management, and resource allocation. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects on weight loss in adults of replacing diet beverages with water during a hypoenergetic diet: a randomized, 24-wk clinical trial.

PubMed

Madjd, Ameneh; Taylor, Moira A; Delavari, Alireza; Malekzadeh, Reza; Macdonald, Ian A; Farshchi, Hamid R

2015-12-01

Obese people believe that drinking diet beverages (DBs) may be a simple strategy to achieve weight loss. However, nutritionists advise drinking water when attempting to lose weight. It is unclear how important drinking water instead of DBs is during a weight-loss program. In this study, we compared the effect on weight loss of either replacing DBs with water or continuing to consume DBs in adults during a 24-wk weight-loss program. Overweight and obese women [n = 89; body mass index (BMI; in kg/m(2)): 27-40; age: 18-50 y] who usually consumed DBs in their diet were asked to either substitute water for DBs (water group) or continue drinking DBs 5 times/wk after their lunch for 24 wk (DB group) while on a weight-loss program. Sixty-two participants (71%) completed the trial (32 in the DB group, 30 in the water group). Baseline variables were not statistically significantly different between groups. A statistically significant reduction in anthropometric measurements and statistically significant improvements in cardiometabolic risk characteristics were observed over 24 wk in both groups. Compared with the DB group, the water group had a greater decrease in weight (mean ± SD: water: -8.8 ± 1.9 kg; DBs: -7.6 ± 2.1 kg; P = 0.015, time × group), fasting insulin (mean ± SD: water: -2.84 ± 0.77 mU/L; DBs: -1.78 ± 1.25 mU/L, P < 0.001), homeostasis model assessment of insulin resistance (mean ± SD: water: -0.097 ± 0.049; DBs: -0.057 ± 0.042, P < 0.001), and 2-h postprandial glucose (mean ± SD: water: -1.02 ± 0.25 mmol/L; DBs: -0.72 ± 0.27 mmol/L; P < 0.001) over the 24 wk. However, there was no significant time × group interaction for waist circumference, fasting plasma glucose, and lipid profiles within both groups over 24 wk. Replacement of DBs with water after the main meal may lead to greater weight reduction during a weight-loss program. It may also offer clinical benefits to improve insulin resistance. This trial was registered at www.irct.ir/ as IRCT201402177754N5. © 2015 American Society for Nutrition.

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

PubMed

Wichmann, Thomas; DeLong, Mahlon R

2016-04-01

Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index

PubMed Central

Hacker, Mallory L.; Turchan, Maxim; Molinari, Anna L.; Currie, Amanda D.

2017-01-01

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50–75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT (n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t-tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (p > 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = −0.89; DBS+ODT = −0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152). PMID:28676842

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

PubMed

Millan, Sarah H; Hacker, Mallory L; Turchan, Maxim; Molinari, Anna L; Currie, Amanda D; Charles, David

2017-01-01

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT ( n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t -tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group ( p > 0.05). BMI change over two years was not different between the groups ( p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

PubMed

Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

2017-03-01

Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

Dried blood spot analysis for therapeutic drug monitoring of pazopanib.

PubMed

de Wit, Djoeke; den Hartigh, Jan; Gelderblom, Hans; Qian, Yanwen; den Hollander, Margret; Verheul, Henk; Guchelaar, Henk-Jan; van Erp, Nielka P

2015-12-01

Dried blood spot (DBS) sampling is potentially a more patient-friendly and flexible alternative to venous sampling of pazopanib. This study determined the agreement between pazopanib DBS and plasma concentrations to facilitate implementation of pazopanib DBS sampling into clinical practice. Paired DBS and plasma samples were collected in 12 patients. Pazopanib plasma concentrations were calculated from DBS concentrations using the formula: plasma concentration = DBSconcentration /(1 - hematocrit). Passing-Bablok and Bland-Altman analyses were used to determine the agreement between calculated and measured plasma concentrations. We predefined a clinical acceptance limit of 25% for the Bland-Altman analysis. Passing-Bablok analysis showed a small constant (intercept estimate, -8.53 [95%CI, -12.22 to -4.41]) and slightly proportional (slope estimate, 1.15 [95%CI, 1.04-1.24]) bias between calculated and measured concentrations. This bias was clinically nonrelevant, as shown by Bland-Altman analysis; the mean ratio of calculated to measured concentrations was 0.94 (95%CI, 0.65-1.23). The clinical acceptance limits were well within these 95% limits of agreement. More specifically, 92.6% of the data points were within the predefined acceptance limits. Pazopanib plasma concentrations can be accurately calculated from DBS concentrations. Although validation of DBS cards prepared by patients themselves is required, these results show that DBS sampling can be used to monitor pazopanib therapy in clinical practice. © 2015, The American College of Clinical Pharmacology.

The Dominance Behavioral System and Psychopathology: Evidence from Self-Report, Observational, and Biological Studies

PubMed Central

Johnson, Sheri L.; Leedom, Liane J.; Muhtadie, Luma

2012-01-01

The dominance behavioral system (DBS) can be conceptualized as a biologically-based system which guides dominance motivation, dominant and subordinate behavior, and responsivity to perceptions of power and subordination. A growing body of research suggests that problems with the DBS are evident across a broad range of psychopathologies. We begin by describing psychological, social, and biological correlates of the dominance behavioral system (DBS). Extensive research suggests that externalizing disorders, mania-proneness, and narcissistic traits are related to heightened dominance motivation and behaviors. Mania and narcissistic traits also appear related to inflated self-perceptions of power. Anxiety and depression are related to subordination and submissiveness, as well as a desire to avoid subordination. Models of the DBS have received support from research with humans and animals; from self-report, observational, and biological methods; and using naturalistic and experimental paradigms. Limitations of available research include the relative lack of longitudinal studies using multiple measures of the DBS and the absence of relevant studies using diagnosed samples to study narcissistic personality disorder and bipolar disorder. We provide suggestions for future research on the DBS and psychopathology, including investigations of whether the DBS can be used to differentiate specific disorder outcomes; the need for more sophisticated biological research; and the value of longitudinal dynamical research. Implications of using the DBS as a tool in clinical assessment and treatment are discussed. PMID:22506751

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case-control study.

PubMed

Strowd, Roy E; Herco, Maja; Passmore-Griffin, Leah; Avery, Bradley; Haq, Ihtsham; Tatter, Stephen B; Tate, Jessica; Siddiqui, Mustafa S

2016-01-01

To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of subthalamic nucleus stimulation during exercise on the mesolimbocortical dopaminergic region in Parkinson's disease: a positron emission tomography study.

PubMed

Nozaki, Takao; Sugiyama, Kenji; Yagi, Shunsuke; Yoshikawa, Etsuji; Kanno, Toshihiko; Asakawa, Tetsuya; Ito, Tae; Terada, Tatsuhiro; Namba, Hiroki; Ouchi, Yasuomi

2013-03-01

To elucidate the dynamic effects of deep brain stimulation (DBS) in the subthalamic nucleus (STN) during activity on the dopaminergic system, 12 PD patients who had STN-DBS operations at least 1 month prior, underwent two positron emission tomography scans during right-foot movement in DBS-off and DBS-on conditions. To quantify motor performance changes, the motion speed and mobility angle of the foot at the ankle were measured twice. Estimations of the binding potential of [(11)C]raclopride (BP(ND)) were based on the Logan plot method. Significant motor recovery was found in the DBS-on condition. The STN-DBS during exercise significantly reduced the [(11)C]raclopride BP(ND) in the caudate and the nucleus accumbens (NA), but not in the dorsal or ventral putamen. The magnitude of dopamine release in the NA correlated negatively with the magnitude of motor load, indicating that STN-DBS facilitated motor behavior more smoothly and at less expense to dopamine neurons in the region. The lack of dopamine release in the putamen and the significant dopamine release in the ventromedial striatum by STN-DBS during exercise indicated dopaminergic activation occurring in the motivational circuit during action, suggesting a compensatory functional activation of the motor loop from the nonmotor to the motor loop system.

[Deep brain stimulation - expectations and doubts. A nationwide questionnaire study of patients with Parkinson's disease and their family members].

PubMed

Südmeyer, M; Volkmann, J; Wojtecki, L; Deuschl, G; Schnitzler, A; Möller, B

2012-04-01

The aim of this questionnaire-based study was to determine the decision-making motives from Parkinson's patients and their family members for deep brain stimulation (DBS), which are crucial for the attitude towards this therapy and which should be considered during the clinical interview. The questionnaire was sent out nationwide to members of the German Parkinson Association. Patient and family specific data as well as information sources, doubts and expectations with respect to DBS were assessed. A total of 582 patients and 476 family members answered the questionnaire, revealing that 96% of the patients and 91% of the family members already possessed information regarding DBS. While a large proportion of interviewees had specific expectations concerning DBS, more than two thirds expressed concerns regarding DBS; the most frequent with respect to intraoperative complications and stimulation-induced worsening of symptoms. The quantity of realistic patients and family expectations significantly correlated with a positive evaluation of DBS and doubts as well as unrealistic expectations of family members correlated with a negative attitude towards the operation. The findings suggest that patients and their relatives organized in support groups indeed possess detailed information regarding DBS. However, for the acceptance of the treatment a timely elucidation about DBS as well as responding to the individual concerns by the consulting physician is essential.

What parents think and feel about deep brain stimulation in paediatric secondary dystonia including cerebral palsy: A qualitative study of parental decision-making.

PubMed

Austin, Allana; Lin, Jean-Pierre; Selway, Richard; Ashkan, Keyoumars; Owen, Tamsin

2017-01-01

Dystonia is characterised by involuntary movements and postures. Deep Brain Stimulation (DBS) is effective in reducing dystonic symptoms in primary dystonia in childhood and to lesser extent in secondary dystonia. How families and children decide to choose DBS surgery has never been explored. To explore parental decision-making for DBS in paediatric secondary dystonia. Data was gathered using semi-structured interviews with eight parents of children with secondary dystonia who had undergone DBS. Interviews were analysed using Interpretative Phenomenological Analysis. For all parents the decision was viewed as significant, with life altering consequences for the child. These results suggested that parents were motivated by a hope for a better life and parental duty. This was weighed against consideration of risks, what the child had to lose, and uncertainty of DBS outcome. Decisions were also influenced by the perspectives of their child and professionals. The decision to undergo DBS was an ongoing process for parents, who ultimately were struggling in the face of uncertainty whilst trying to do their best as parents for their children. These findings have important clinical implications given the growing referrals for consideration of DBS childhood dystonia, and highlights the importance of further quantitative research to fully establish the efficacy of DBS in secondary dystonia to enhance informed decision-making. Copyright © 2016. Published by Elsevier Ltd.

Deep brain stimulation of pedunculopontine tegmental nucleus: role in sleep modulation in advanced Parkinson disease patients: one-year follow-up.

PubMed

Peppe, Antonella; Pierantozzi, Mariangela; Baiamonte, Valentina; Moschella, Vincenzo; Caltagirone, Carlo; Stanzione, Paolo; Stefani, Alessandro

2012-12-01

Sleep disorders are frequent non-motor symptoms in Parkinson disease (PD), probably due to multifactorial pathogeneses including disease progression, dopaminergic drugs, or concomitant illness. In recent years, the pedunculopontine tegmental (PPTg) nucleus has been considered a surgical target for deep brain stimulation (DBS) in advanced PD patients. As it is involved in controlling the sleep-wake cycle, we investigated the long-lasting effects of PPTg-DBS on the sleep of five PD patients implanted in both the PPTg and the subthalamic nucleus (STN) by rating two subjective clinical scales for sleep: the Parkinson's Disease Sleep Scale (PDSS), and the Epworth Sleepiness Scale (ESS). Sleep scales were administered a week before surgery (T0), three months after DBS (T1), and one year later (T2). In this study, STN-DBS was kept constantly in ON, and three different patterns of PPTg-DBS were investigated: STN-ON (PPTg switched off); PPTg-ON (PPTg stimulated 24 h/day); PPTg-cycle (PPTg stimulated only at night). In post-surgery follow-up, PD patients reported a marked improvement of sleep quality in all DBS conditions. In particular, stimulation of the PPTg nucleus produced not only a remarkable long-term improvement of nighttime sleep, but unlike STN-DBS, also produced significant amelioration of daytime sleepiness. Our study suggests that PPTg-DBS plays an important role in reorganizing regular sleep in PD patients.

The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

PubMed

Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

2015-08-01

Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

PubMed

Liu, Yi; Li, Weina; Tan, Changhong; Liu, Xi; Wang, Xin; Gui, Yuejiang; Qin, Lu; Deng, Fen; Hu, Changlin; Chen, Lifen

2014-09-01

Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long-term observations on therapeutic effects are needed.

47 CFR 25.164 - Milestones.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and DARS...

47 CFR 25.164 - Milestones.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and DARS...

47 CFR 25.164 - Milestones.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and DARS...

47 CFR 25.164 - Milestones.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and DARS...

Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

PubMed

Elgebaly, Ahmed; Elfil, Mohamed; Attia, Attia; Magdy, Mayar; Negida, Ahmed

2018-02-01

Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

Short circuit in deep brain stimulation.

PubMed

Samura, Kazuhiro; Miyagi, Yasushi; Okamoto, Tsuyoshi; Hayami, Takehito; Kishimoto, Junji; Katano, Mitsuo; Kamikaseda, Kazufumi

2012-11-01

The authors undertook this study to investigate the incidence, cause, and clinical influence of short circuits in patients treated with deep brain stimulation (DBS). After the incidental identification of a short circuit during routine follow-up, the authors initiated a policy at their institution of routinely evaluating both therapeutic impedance and system impendence at every outpatient DBS follow-up visit, irrespective of the presence of symptoms suggesting possible system malfunction. This study represents a report of their findings after 1 year of this policy. Implanted DBS leads exhibiting short circuits were identified in 7 patients (8.9% of the patients seen for outpatient follow-up examinations during the 12-month study period). The mean duration from DBS lead implantation to the discovery of the short circuit was 64.7 months. The symptoms revealing short circuits included the wearing off of therapeutic effect, apraxia of eyelid opening, or dysarthria in 6 patients with Parkinson disease (PD), and dystonia deterioration in 1 patient with generalized dystonia. All DBS leads with short circuits had been anchored to the cranium using titanium miniplates. Altering electrode settings resulted in clinical improvement in the 2 PD cases in which patients had specific symptoms of short circuits (2.5%) but not in the other 4 cases. The patient with dystonia underwent repositioning and replacement of a lead because the previous lead was located too anteriorly, but did not experience symptom improvement. In contrast to the sudden loss of clinical efficacy of DBS caused by an open circuit, short circuits may arise due to a gradual decrease in impedance, causing the insidious development of neurological symptoms via limited or extended potential fields as well as shortened battery longevity. The incidence of short circuits in DBS may be higher than previously thought, especially in cases in which DBS leads are anchored with miniplates. The circuit impedance of DBS should be routinely checked, even after a long history of DBS therapy, especially in cases of miniplate anchoring.

Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

PubMed

Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

Comparison of cross-sectional HIV incidence assay results from dried blood spots and plasma.

PubMed

Schlusser, Katherine E; Pilcher, Christopher; Kallas, Esper G; Santos, Breno R; Deeks, Steven G; Facente, Shelley; Keating, Sheila M; Busch, Michael P; Murphy, Gary; Welte, Alex; Quinn, Thomas; Eshleman, Susan H; Laeyendecker, Oliver

2017-01-01

Assays have been developed for cross-sectional HIV incidence estimation using plasma samples. Large scale surveillance programs are planned using dried blood spot (DBS) specimens for incidence assessment. However, limited information exists on the performance of HIV cross-sectional incidence assays using DBS. The assays evaluated were: Maxim HIV-1 Limiting Antigen Avidity EIA (LAg-Avidity), Sedia HIV-1 BED-Capture EIA (BED-CEIA), and CDC modified BioRad HIV-1/2 Plus O Avidity-based Assay (CDC-BioRad Avidity) using pre-determined cutoff values. 100 matched HIV-1 positive plasma and DBS samples, with known duration of infection, from the Consortium for the Evaluation and Performance of HIV Incidence Assays repository were tested. All assays were run in duplicate. To examine the degree of variability within and between results for each sample type, both categorical and continuous results were analyzed. Associations were assessed with Bland Altman, R2 values and Cohen's kappa coefficient (ĸ). Intra-assay variability using the same sample type was similar for all assays (R2 0.96 to 1.00). The R2 values comparing DBS and plasma results for LAg-Avidity, BED-CEIA, and CDC-BioRad Avidity were 0.96, 0.94, and 0.84, respectively. The concordance and ĸ values between DBS and plasma for all three assays were >87% and >0.64, respectively. The Bland-Altman analysis showed significant differences between plasma and DBS samples. For all three assays, a higher number of samples were classified as recent infections using DBS samples. DBS and plasma sample results were highly correlated. However, when compared to plasma, each assay performed somewhat differently in DBS at the lower and higher ends of the dynamic range. DBS samples were more likely to be classified as recently infected by all three assays, which may lead to overestimation of incidence in surveys using performance criteria derived for plasma samples.

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.

PubMed

Ross, Erika K; Kim, Joo Pyung; Settell, Megan L; Han, Seong Rok; Blaha, Charles D; Min, Hoon-Ki; Lee, Kendall H

2016-03-01

Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop. Copyright © 2016 Elsevier Inc. All rights reserved.

Performance characteristics of finger-stick dried blood spots (DBS) on the determination of human immunodeficiency virus (HIV) treatment failure in a pediatric population in Mozambique

PubMed Central

Chang, Joy; de Sousa, Amina; Sabatier, Jennifer; Assane, Mariamo; Zhang, Guoqing; Bila, Dulce; Vaz, Paula; Alfredo, Charity; Cossa, Loide; Bhatt, Nilesh; Koumans, Emilia H.; Yang, Chunfu; Rivadeneira, Emilia; Jani, Ilesh; Houston, James C.

2017-01-01

Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott’s VL test with a paired plasma sample using Roche’s VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing. PMID:28704560

Hierarchical colorant-based direct binary search halftoning.

PubMed

He, Zhen

2010-07-01

Colorant-based direct binary search (CB-DBS) halftoning proposed in provides an image quality benchmark for dispersed-dot halftoning algorithms. The objective of this paper is to further push the image quality limit. An algorithm called hierarchical colorant-based direct binary search (HCB-DBS) is developed in this paper. By appropriately integrating yellow colorant into dot-overlapping and dot-positioning controls, it is demonstrated that HCB-DBS can achieve better halftone texture of both individual and joint dot-color planes, without compromising the dot distribution of more visible halftone of cyan and magenta colorants. The input color specification is first converted from colorant space to dot-color space with minimum brightness variation principle for full dot-overlapping control. The dot-colors are then split into groups based upon dot visibility. Hierarchical monochrome DBS halftoning is applied to make dot-positioning decision for each group, constrained on the already generated halftone of the groups with higher priority. And dot-coloring is decided recursively with joint monochrome DBS halftoning constrained on the related total dot distribution. Experiments show HCB-DBS improves halftone texture for both individual and joint dot-color planes. And it reduces the halftone graininess and free of color mottle artifacts, comparing to CB-DBS.

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor.

PubMed

Resnick, Andrew S; Okun, Michael S; Malapira, Teresita; Smith, Donald; Vale, Fernando L; Sullivan, Kelly; Miller, Amber; Jahan, Israt; Zesiewicz, Theresa

2012-01-01

Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. The data from this study indicate that medication cessation is common following unilateral DBS for ET.

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor

PubMed Central

Resnick, Andrew S.; Okun, Michael S.; Malapira, Teresita; Smith, Donald; Vale, Fernando L.; Sullivan, Kelly; Miller, Amber; Jahan, Israt; Zesiewicz, Theresa

2012-01-01

Background Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. Methods We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Results Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. Discussion The data from this study indicate that medication cessation is common following unilateral DBS for ET. PMID:23440408

Effect of storage conditions on the weight and appearance of dried blood spot samples on various cellulose-based substrates.

PubMed

Denniff, Philip; Spooner, Neil

2010-11-01

Before shipping and storage, dried blood spot (DBS) samples must be dried in order to protect the integrity of the spots. In this article, we examine the time required to dry blood spot samples and the effects of different environmental conditions on their integrity. Under ambient laboratory conditions, DBS samples on Whatman 903(®), FTA(®) and FTA(®) Elute substrates are dry within 90 min of spotting. An additional 5% of moisture is lost during subsequent storage with desiccant. When exposed to elevated conditions of temperature and relative humidity, the DBS samples absorb moisture. DBS samples on FTA lose this moisture on being returned to ambient conditions. DBS samples on 903 show no visible signs of deterioration when stored at elevated conditions. However, these conditions cause the DBS to diffuse through the FTA Elute substrate. Blood spots are dry within 90 min of spotting. However, the substrates examined behave differently when exposed to conditions of high relative humidity and temperature, in some cases resulting in the integrity of the substrate and DBS sample being compromised. It is recommended that these factors be investigated as part of method development and validation.

Effects of dopaminergic and subthalamic stimulation on musical performance.

PubMed

van Vugt, Floris T; Schüpbach, Michael; Altenmüller, Eckart; Bardinet, Eric; Yelnik, Jérôme; Hälbig, Thomas D

2013-05-01

Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

Telecommunications: Issues in Providing Cable and Satellite Television Services

NASA Astrophysics Data System (ADS)

2002-10-01

This report provides information on (1) whether the availability of cable modem Internet access service appears to be affecting the competitiveness of direct broadcast satellite (DBS) companies in the provision of video services, (2) whether cable prices and DBS penetration rates appear to be affected in areas where the DBS companies offer local broadcast channels, and (3) whether the two individual DBS companies are technologically capable of expanding local broadcast channel services into all 210 television markets in the United States.

Articulation Features of Parkinson's Disease Patients with Subthalamic Nucleus Deep Brain Stimulation.

PubMed

Tanaka, Yasuhiro; Tsuboi, Takashi; Watanabe, Hirohisa; Kajita, Yasukazu; Nakatsubo, Daisuke; Fujimoto, Yasushi; Ohdake, Reiko; Ito, Mizuki; Atsuta, Naoki; Yamamoto, Masahiko; Wakabayashi, Toshihiko; Katsuno, Masahisa; Sobue, Gen

2016-10-19

Voice and speech disorders are one of the most important issues after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. However, articulation features in this patient population remain unclear. We studied the articulation features of PD patients with STN-DBS. Participants were 56 PD patients treated with STN-DBS (STN-DBS group) and 41 patients treated only with medical therapy (medical-therapy-alone group). Articulation function was evaluated with acoustic and auditory-perceptual analyses. The vowel space area (VSA) was calculated using the formant frequency data of three vowels (/a/, /i/, and /u/) from sustained phonation task. The VSA reportedly reflects the distance of mouth/jaw and tongue movements during speech and phonation. Correlations between acoustic and auditory-perceptual measurements were also assessed. The VSA did not significantly differ between the medical-therapy-alone group and the STN-DBS group in the off-stimulation condition. In the STN-DBS group, the VSA was larger in the on-stimulation condition than in the off-stimulation condition. However, individual analysis showed the VSA changes after stopping stimulation were heterogeneous. In total, 89.8% of the STN-DBS group showed a large VSA size in the on- than in the off-stimulation condition. In contrast, the VSA of the remaining patients in that group was smaller in the on- than the off-stimulation condition. STN-DBS may resolve hypokinesia of the articulation structures, including the mouth/jaw and tongue, and improve maximal vowel articulation. However, in the on-stimulation condition, the VSA was not significantly correlated with speech intelligibility. This may be because STN-DBS potentially affects other speech processes such as voice and/or respiratory process.

Identification of the Doublesex protein binding sites that activate expression of lozenge in the female genital disc in Drosophila melanogaster.

PubMed

Wagamitsu, Shunsuke; Takase, Dan; Aoki, Fugaku; Suzuki, Masataka G

2017-02-01

Normal sexual differentiation in the genital organs is essential for the animal species that use sexual reproduction. Although it is known that doublesex (dsx) is required for the sexual development of the genitalia in various insect species, the direct target genes responsible for the sexual differentiation of the genitalia have not been identified. The lozenge (lz) gene is expressed in the female genital disc and is essential for developments of spermathecae and accessory glands in Drosophila melanogaster. The female-specific isoform of DSX (DSXF) is required for activating lz expression in the female genital disc. However, it still remains unclear whether the DSXF directly activates the transcription of lz in the female genital disc. In this study, we found two sequences (lz-DBS1 and lz-DBS2) within lz locus that showed high homoloty to the DSX binding motif identified previously. Competition assays using recombinant DSX DNA-binding domain (DSX-DBD) protein verified that the DSX-DBD protein bound to lz-DBS1 and lz-DBS2 in a sequence-specific manner with lower affinity than to the known DSX binding site in the bric-à-brac 1 (bab1) gene. Reporter gene analyses revealed that a 2.5-kbp lz genomic fragment containing lz-DBS1 and lz-DBS2 drove reporter gene (EGFP) expression in a manner similar to endogenous lz expression in the female genital disc. Mutations in lz-DBS1 alone significantly reduced the area of EGFP-expressing region, while EGFP expression in the female genital disc was abolished when both sites were mutated. These results demonstrated that DSX directly activates female-specific lz expression in the genital disc through lz-DBS1 and lz-DBS2. Copyright © 2017 Elsevier B.V. All rights reserved.

The Ethanol-Induced Stimulation of Rat Duodenal Mucosal Bicarbonate Secretion In Vivo Is Critically Dependent on Luminal Cl–

PubMed Central

Sommansson, Anna; Wan Saudi, Wan Salman; Nylander, Olof; Sjöblom, Markus

2014-01-01

Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl− from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl− and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms. PMID:25033198

Impulsive and compulsive behaviors in Parkinson Study Group (PSG) centers performing deep brain stimulation surgery.

PubMed

Hack, Nawaz; Akbar, Umer; Thompson-Avila, Amanda; Fayad, Sarah M; Hastings, Erin M; Moro, Elena; Nestor, Kelsey; Ward, Herbert; York, Michele; Okun, Michael S

2014-01-01

Impulse control disorders (ICDs), dopamine dysregulation syndrome (DDS), and dopamine agonist withdrawal syndrome (DAWS) have been reported commonly in Parkinson's disease (PD) populations. The treatment approaches may be widely variable and there is not much information on these syndromes in the setting of deep brain stimulation (DBS). To evaluate (1) ICDs, DAWS and DDS pre- and post DBS in PD and (2) to investigate pre-DBS treatment strategies regarding these behaviors among Parkinson Study Group (PSG) centers. Forty-eight PSG centers were surveyed on ICDs, DAWS and DDS, as well as on potential relationships to DBS and treatment approaches. Sixty-seven percent of PSG centers reported that they served a population of over 500 PD patients per year, and 94% of centers performed DBS surgery. Most centers (92%) reported screening for ICDs, DAWS and DDS. Of the centers screening for these symptoms, 13% reported always employing a formal battery of pre-operative tests, 46% of sites inconsistently used a formal battery, while 23% of sites reported never using a formal battery to screen for these symptoms. The estimated numbers of centers observing ICDs, DAWS and DDS pre-operatively in individuals with PD were 71%, 69%, and 69%, respectively. PSG DBS centers observing at least one case of a new de novo occurrence of an ICD, DAWS or DDS after DBS surgery were 67%, 65% and 65%, respectively. The results suggest that addiction-like syndromes and withdrawal syndromes are prevalent in expert PSG centers performing DBS. Most centers reported screening for these issues without the use of a formal battery, and there were a large number of centers reporting ICDs, DAWS and DDS post-DBS. A single treatment strategy did not emerge.

Betting on DBS: Effects of Subthalamic Nucleus Deep Brain Stimulation on Risk-Taking and Decision-Making in Patients with Parkinson’s Disease

PubMed Central

Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C.; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

2014-01-01

Objective Concerns persist that deep brain stimulation (DBS) for Parkinson’s disease (PD) increases impulsivity and/or induces excessive reward-seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on three laboratory tasks of risk-taking and decision-making. They are compared to PD patients maintained on medication and normal control subjects. Methods and Results In the Game of Dice Task, a test of “risky” decision-making, PD patients with or without DBS made highest-risk bets more often, and ended up with less money, than normal controls. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an “ambiguous” decision-making task that assessed preference for risk (holding on to one’s briefcase) over a “sure thing” (accepting the banker’s offer). Here, DBS patients were more conservative with stimulation on than off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the two PD groups won less money than healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was “framed” as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than normal subjects, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. Conclusions On “risky” decision-making tasks, DBS patients were more risk-taking than normal, but stimulation may temper this tendency. In contrast, in an “ambiguous risk” situation, DBS patients were more risk-averse (conservative) than normal, and this tendency was greatest with stimulation. PMID:25486385

The ethanol-induced stimulation of rat duodenal mucosal bicarbonate secretion in vivo is critically dependent on luminal Cl-.

PubMed

Sommansson, Anna; Wan Saudi, Wan Salman; Nylander, Olof; Sjöblom, Markus

2014-01-01

Alcohol may induce metabolic and functional changes in gastrointestinal epithelial cells, contributing to impaired mucosal barrier function. Duodenal mucosal bicarbonate secretion (DBS) is a primary epithelial defense against gastric acid and also has an important function in maintaining the homeostasis of the juxtamucosal microenvironment. The aim in this study was to investigate the effects of the luminal perfusion of moderate concentrations of ethanol in vivo on epithelial DBS, fluid secretion and paracellular permeability. Under thiobarbiturate anesthesia, a ∼30-mm segment of the proximal duodenum with an intact blood supply was perfused in situ in rats. The effects on DBS, duodenal transepithelial net fluid flux and the blood-to-lumen clearance of 51Cr-EDTA were investigated. Perfusing the duodenum with isotonic solutions of 10% or 15% ethanol-by-volume for 30 min increased DBS in a concentration-dependent manner, while the net fluid flux did not change. Pre-treatment with the CFTR inhibitor CFTRinh172 (i.p. or i.v.) did not change the secretory response to ethanol, while removing Cl- from the luminal perfusate abolished the ethanol-induced increase in DBS. The administration of hexamethonium (i.v.) but not capsazepine significantly reduced the basal net fluid flux and the ethanol-induced increase in DBS. Perfusing the duodenum with a combination of 1.0 mM HCl and 15% ethanol induced significantly greater increases in DBS than 15% ethanol or 1.0 mM HCl alone but did not influence fluid flux. Our data demonstrate that ethanol induces increases in DBS through a mechanism that is critically dependent on luminal Cl- and partly dependent on enteric neural pathways involving nicotinic receptors. Ethanol and HCl appears to stimulate DBS via the activation of different bicarbonate transporting mechanisms.

Betting on DBS: Effects of subthalamic nucleus deep brain stimulation on risk taking and decision making in patients with Parkinson's disease.

PubMed

Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

2015-07-01

Concerns persist that deep brain stimulation (DBS) for Parkinson's disease (PD) increases impulsivity or induces excessive reward seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on 3 laboratory tasks of risk taking and decision making. They are compared with PD patients maintained on medication and healthy participants. In the Game of Dice Task, a test of "risky" decision making, PD patients with or without DBS made highest risk bets more often and ended up with less money than did healthy participants. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an "ambiguous" decision-making task that assessed preference for risk (holding on to one's briefcase) over a "sure thing" (accepting the banker's offer). Here, DBS patients were more conservative with stimulation on than with it off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the 2 PD groups won less money than did healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was "framed" as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than were healthy participants, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. On risky decision-making tasks, DBS patients took more risks than did healthy participants, but stimulation may temper this tendency. In contrast, in an ambiguous-risk situation, DBS patients were more risk-averse (conservative) than were healthy participants, and this tendency was greatest with stimulation. (c) 2015 APA, all rights reserved).

Deep Brain Stimulation for Parkinson Disease in the Philippines: Outcomes of the Philippine Movement Disorder Surgery Center.

PubMed

Diestro, Jose Danilo B; Vesagas, Theodor S; Teleg, Rosalia A; Aguilar, Jose A; Anlacan, Joseph P; Jamora, Roland Dominic G

2018-04-28

Deep brain stimulation (DBS) is an established treatment modality for Parkinson disease (PD). The first DBS for PD in the Philippines was performed at the Philippine Movement Disorder Surgery Center in 2006. There are no Philippine data on DBS for PD. We aim to determine the motor improvement and reduction in medication dosage of all patients with PD who underwent DBS at the Philippine Movement Disorder Surgery Center. This is a retrospective study of all patients with PD (n = 17) who underwent DBS from 2006 to 2016. The change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor and levodopa equivalent dose were determined. There was a statistically significant reduction in the UPDRS motor in all patients off medication at 3 months (48.2%; P = 0.004), 1 year (47.3%; P = 0.026), 2 years (48.4%; P = 0.021), and 3 years (66.0%; P = 0.032) after DBS and on medication at 3 months (43.3%; P = 0.023), 6 months (24.7%; P = 0.053), and 1 year (38.1%; P = 0.033). A significant reduction in the dosage of PD medications was also seen until the second year of follow-up (52.3%; P < 0.001). Adverse events included an attempted suicide and a device-related infection. DBS for PD improves the UPDRS motor score in the off-medication and on-medication state, with the maximal benefit seen at 3 years after surgery and reduces PD medication dosage by half. Although the benefit from DBS is undeniable, the high cost of the procedure precludes more patients from benefitting from it. There is a need for government support to expand access to DBS. Copyright © 2018 Elsevier Inc. All rights reserved.

Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum.

PubMed

Mizumori, Misa; Ham, Maggie; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

2009-07-15

Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO(3-) surface microclimate pH regulatory system effectively protects the mucosa from acid injury.

Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson's Disease.

PubMed

Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

2015-01-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson's disease (PD). However, some aspects of executive control are impaired with STN DBS. We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

MEG Can Map Short and Long-Term Changes in Brain Activity following Deep Brain Stimulation for Chronic Pain

PubMed Central

Mohseni, Hamid R.; Smith, Penny P.; Parsons, Christine E.; Young, Katherine S.; Hyam, Jonathan A.; Stein, Alan; Stein, John F.; Green, Alexander L.; Aziz, Tipu Z.; Kringelbach, Morten L.

2012-01-01

Deep brain stimulation (DBS) has been shown to be clinically effective for some forms of treatment-resistant chronic pain, but the precise mechanisms of action are not well understood. Here, we present an analysis of magnetoencephalography (MEG) data from a patient with whole-body chronic pain, in order to investigate changes in neural activity induced by DBS for pain relief over both short- and long-term. This patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). We demonstrate that a novel method, null-beamforming, can be used to localise accurately brain activity despite the artefacts caused by the presence of DBS electrodes and stimulus pulses. The accuracy of our source localisation was verified by correlating the predicted DBS electrode positions with their actual positions. Using this beamforming method, we examined changes in whole-brain activity comparing pain relief achieved with deep brain stimulation (DBS ON) and compared with pain experienced with no stimulation (DBS OFF). We found significant changes in activity in pain-related regions including the pre-supplementary motor area, brainstem (periaqueductal gray) and dissociable parts of caudal and rostral ACC. In particular, when the patient reported experiencing pain, there was increased activity in different regions of ACC compared to when he experienced pain relief. We were also able to demonstrate long-term functional brain changes as a result of continuous DBS over one year, leading to specific changes in the activity in dissociable regions of caudal and rostral ACC. These results broaden our understanding of the underlying mechanisms of DBS in the human brain. PMID:22675503

Use of finger-prick dried blood spots (fpDBS) and capillary electrophoresis for carbohydrate deficient transferrin (CDT) screening in forensic toxicology.

PubMed

Bertaso, Anna; Sorio, Daniela; Vandoros, Anthula; De Palo, Elio F; Bortolotti, Federica; Tagliaro, Franco

2016-10-01

Continued progress in chronic alcohol abuse investigation requires the development of less invasive procedures for screening purposes. The application of finger-prick and related dried blood spots (fpDBS) for carbohydrate deficient transferrin (CDT) detection appears suitable for this aim. Therefore, the goal of this project was to develop a screening method for CDT using fpDBS with CZE analysis. Blood samples prepared by finger-prick were placed on DBS cards and left to air dry; each dried fpDBS disc was shredded into small pieces and suspended in acid solution (60 μL of HCl 120 mmol/L). After centrifugation (10 min at 1500 × g), the collected sample was adjusted to pH 3.5. After an overnight incubation, the pH was neutralised and an iron rich solution was added. After 1 h, CZE analysis was carried out. A group of 47 individuals was studied. Parallel serum samples were collected from each investigated subject and the %CDT for each sample was measured using HPLC and CZE techniques. The fpDBS transferrin sialo isoform electropherograms were similar to those obtained with serum. Moreover, fpDBS CZE CDT percentage levels demonstrated significant statistical correlation with those obtained from serum for both HPLC and CZE %CDT (p < 0.01; r 2 = 0.8913 and 0.8976, respectively), with %CDT from 0.8 to 13.7% for fpDBS and from 0.7 to 12.7% for serum. The newly developed fpDBS procedure for CDT analysis provides a simple and inexpensive tool for use in population screening. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor

NASA Astrophysics Data System (ADS)

Keane, Maureen; Deyo, Steve; Abosch, Aviva; Bajwa, Jawad A.; Johnson, Matthew D.

2012-08-01

Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.

Behavioral and Neurobiological Effects of Deep Brain Stimulation in a Mouse Model of High Anxiety- and Depression-Like Behavior

PubMed Central

Schmuckermair, Claudia; Gaburro, Stefano; Sah, Anupam; Landgraf, Rainer; Sartori, Simone B; Singewald, Nicolas

2013-01-01

Increasing evidence suggests that high-frequency deep brain stimulation of the nucleus accumbens (NAcb-DBS) may represent a novel therapeutic strategy for individuals suffering from treatment-resistant depression, although the underlying mechanisms of action remain largely unknown. In this study, using a unique mouse model of enhanced depression- and anxiety-like behavior (HAB), we investigated behavioral and neurobiological effects of NAcb-DBS. HAB mice either underwent chronic treatment with one of three different selective serotonin reuptake inhibitors (SSRIs) or received NAcb-DBS for 1 h per day for 7 consecutive days. Animals were tested in established paradigms revealing depression- and anxiety-related behaviors. The enhanced depression-like behavior of HAB mice was not influenced by chronic SSRI treatment. In contrast, repeated, but not single, NAcb-DBS induced robust antidepressant and anxiolytic responses in HAB animals, while these behaviors remained unaffected in normal depression/anxiety animals (NAB), suggesting a preferential effect of NAcb-DBS on pathophysiologically deranged systems. NAcb-DBS caused a modulation of challenge-induced activity in various stress- and depression-related brain regions, including an increase in c-Fos expression in the dentate gyrus of the hippocampus and enhanced hippocampal neurogenesis in HABs. Taken together, these findings show that the normalization of the pathophysiologically enhanced, SSRI-insensitive depression-like behavior by repeated NAcb-DBS was associated with the reversal of reported aberrant brain activity and impaired adult neurogenesis in HAB mice, indicating that NAcb-DBS affects neuronal activity as well as plasticity in a defined, mood-associated network. Thus, HAB mice may represent a clinically relevant model for elucidating the neurobiological correlates of NAcb-DBS. PMID:23325324

Deep brain stimulation for Parkinson's disease: defining the optimal location within the subthalamic nucleus.

PubMed

Bot, Maarten; Schuurman, P Richard; Odekerken, Vincent J J; Verhagen, Rens; Contarino, Fiorella Maria; De Bie, Rob M A; van den Munckhof, Pepijn

2018-05-01

Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably. Stereotactic targeting of the dorsolateral sensorimotor part of the STN is considered paramount for maximising effectiveness, but studies employing the midcommissural point (MCP) as anatomical reference failed to show correlation between DBS location and motor improvement. The medial border of the STN as reference may provide better insight in the relationship between DBS location and clinical outcome. Motor improvement after 12 months of 65 STN DBS electrodes was categorised into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS 'hotspots'. Using the medial STN border as reference, significant negative correlation (Pearson's correlation -0.52, P<0.01) was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found. The medial STN border proved superior compared with MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. We therefore propose the medial STN border as a better individual reference point than the currently used MCP on preoperative stereotactic imaging, in order to obtain optimal and thus less variable motor improvement for individual patients with PD following STN DBS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback

PubMed Central

Van Gompel, Jamie J.; Chang, Su-Youne; Goerss, Stephan J.; Kim, In Yong; Kimble, Christopher; Bennet, Kevin E.; Lee, Kendall H.

2010-01-01

Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a “smart” DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans. PMID:20672923

Subthalamic nucleus deep brain stimulation improves somatosensory function in Parkinson's disease.

PubMed

Aman, Joshua E; Abosch, Aviva; Bebler, Maggie; Lu, Chia-Hao; Konczak, Jürgen

2014-02-01

An established treatment for the motor symptoms of Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Mounting evidence suggests that PD is also associated with somatosensory deficits, yet the effect of STN-DBS on somatosensory processing is largely unknown. This study investigated whether STN-DBS affects somatosensory processing, specifically the processing of tactile and proprioceptive cues, by systematically examining the accuracy of haptic perception of object size. (Haptic perception refers to one's ability to extract object features such as shape and size by active touch.) Without vision, 13 PD patients with implanted STN-DBS and 13 healthy controls haptically explored the heights of 2 successively presented 3-dimensional (3D) blocks using a precision grip. Participants verbally indicated which block was taller and then used their nonprobing hand to motorically match the perceived size of the comparison block. Patients were tested during ON and OFF stimulation, following a 12-hour medication washout period. First, when compared to controls, the PD group's haptic discrimination threshold during OFF stimulation was elevated by 192% and mean hand aperture error was increased by 105%. Second, DBS lowered the haptic discrimination threshold by 26% and aperture error decreased by 20%. Third, during DBS ON, probing with the motorically more affected hand decreased haptic precision compared to probing with the less affected hand. This study offers the first evidence that STN-DBS improves haptic precision, further indicating that somatosensory function is improved by STN-DBS. We conclude that DBS-related improvements are not explained by improvements in motor function alone, but rather by enhanced somatosensory processing. © 2013 Movement Disorder Society.

Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson’s Disease

PubMed Central

Williams, Isobel Anne; Wilkinson, Leonora; Limousin, Patricia; Jahanshahi, Marjan

2015-01-01

Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson’s disease (PD). However, some aspects of executive control are impaired with STN DBS. Objective: We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent. Methods: Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos. Results: The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared. Conclusions: We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing. PMID:25720447

Network effects of deep brain stimulation

PubMed Central

Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

2015-01-01

The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

PubMed

Hescham, Sarah; Jahanshahi, Ali; Schweimer, Judith V; Mitchell, Stephen N; Carter, Guy; Blokland, Arjan; Sharp, Trevor; Temel, Yasin

2016-11-01

Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.

State of the Art: Novel Applications for Deep Brain Stimulation.

PubMed

Roy, Holly A; Green, Alexander L; Aziz, Tipu Z

2018-02-01

Deep brain stimulation (DBS) is a rapidly developing field of neurosurgery with potential therapeutic applications that are relevant to conditions traditionally viewed as beyond the limits of neurosurgery. Our objective, in this review, is to highlight some of the emerging applications of DBS within three distinct but overlapping spheres, namely trauma, neuropsychiatry, and autonomic physiology. An extensive literature review was carried out in MEDLINE, to identify relevant studies and review articles describing applications of DBS in the areas of trauma, neuropsychiatry and autonomic neuroscience. A wide range of applications of DBS in these spheres was identified, some having only been tested in one or two cases, others much better studied. We have identified various avenues for DBS to be applied for patient benefit in cases relevant to trauma, neuropsychiatry and autonomic neuroscience. Further developments in DBS technology and clinical trial design will enable these novel applications to be effectively and rigorously assessed and utilized most effectively. © 2017 International Neuromodulation Society.

Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson's disease.

PubMed

Obeso, Ignacio; Wilkinson, Leonora; Rodríguez-Oroz, Maria-Cruz; Obeso, Jose A; Jahanshahi, Marjan

2013-05-01

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson's disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Parkinson's disease patient preference and experience with various methods of DBS lead placement.

PubMed

LaHue, Sara C; Ostrem, Jill L; Galifianakis, Nicholas B; San Luciano, Marta; Ziman, Nathan; Wang, Sarah; Racine, Caroline A; Starr, Philip A; Larson, Paul S; Katz, Maya

2017-08-01

Physiology-guided deep brain stimulation (DBS) surgery requires patients to be awake during a portion of the procedure, which may be poorly tolerated. Interventional MRI-guided (iMRI) DBS surgery was developed to use real-time image guidance, obviating the need for patients to be awake during lead placement. All English-speaking adults with PD who underwent iMRI DBS between 2010 and 2014 at our Center were invited to participate. Subjects completed a structured interview that explored perioperative preferences and experiences. We compared these responses to patients who underwent the physiology-guided method, matched for age and gender. Eighty-nine people with PD completed the study. Of those, 40 underwent iMRI, 44 underwent physiology-guided implantation, and five underwent both methods. There were no significant differences in baseline characteristics between groups. The primary reason for choosing iMRI DBS was a preference to be asleep during implantation due to: 1) a history of claustrophobia; 2) concerns about the potential for discomfort during the awake physiology-guided procedure in those with an underlying pain syndrome or severe off-medication symptoms; or 3) non-specific fear about being awake during neurosurgery. Participants were satisfied with both DBS surgery methods. However, identification of the factors associated with a preference for iMRI DBS may allow for optimization of patient experience and satisfaction when choices of surgical methods for DBS implantation are available. Published by Elsevier Ltd.

Evidence from a rare case study for Hebbian-like changes in structural connectivity induced by long-term deep brain stimulation.

PubMed

van Hartevelt, Tim J; Cabral, Joana; Møller, Arne; FitzGerald, James J; Green, Alexander L; Aziz, Tipu Z; Deco, Gustavo; Kringelbach, Morten L

2015-01-01

It is unclear whether Hebbian-like learning occurs at the level of long-range white matter connections in humans, i.e., where measurable changes in structural connectivity (SC) are correlated with changes in functional connectivity. However, the behavioral changes observed after deep brain stimulation (DBS) suggest the existence of such Hebbian-like mechanisms occurring at the structural level with functional consequences. In this rare case study, we obtained the full network of white matter connections of one patient with Parkinson's disease (PD) before and after long-term DBS and combined it with a computational model of ongoing activity to investigate the effects of DBS-induced long-term structural changes. The results show that the long-term effects of DBS on resting-state functional connectivity is best obtained in the computational model by changing the structural weights from the subthalamic nucleus (STN) to the putamen and the thalamus in a Hebbian-like manner. Moreover, long-term DBS also significantly changed the SC towards normality in terms of model-based measures of segregation and integration of information processing, two key concepts of brain organization. This novel approach using computational models to model the effects of Hebbian-like changes in SC allowed us to causally identify the possible underlying neural mechanisms of long-term DBS using rare case study data. In time, this could help predict the efficacy of individual DBS targeting and identify novel DBS targets.

Cognitive function in children with primary dystonia before and after deep brain stimulation.

PubMed

Owen, Tamsin; Gimeno, Hortensia; Selway, Richard; Lin, Jean-Pierre

2015-01-01

Dystonia is characterised by involuntary movements (twisting, writhing and jerking) and postures. The effects of deep brain stimulation (DBS) surgery on the motor aspect of primary dystonias have been well reported, however, there is a paucity of research investigating its impact on cognitive function, particularly in childhood dystonia. We performed a follow-up of cognitive function in children with primary dystonia following DBS pallidal surgery. Cognitive function was measured in a cohort of 13 children with primary or primary plus dystonia who had undergone DBS surgery using a retrospective case series design. Baseline pre-DBS neuropsychological measures were compared to scores obtained at least one year following DBS. Cognitive function was assessed using standardised measures of intellectual ability and memory. All children demonstrated improvements with regard to dystonia reduction, as measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Overall, cognition remained stable following DBS in the majority of the cohort. Individual case analysis revealed improvements in some domains of cognitive function in eight members of the cohort and a deterioration of certain domains in four. Cognition largely remained stable in children with primary/primary plus dystonia following DBS surgery, although further research with a larger sample is necessary to explore this statistically. Notwithstanding the limitations of a small size, this preliminary data has potentially positive implications for the impact of DBS on cognitive functioning within a paediatric population. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Direct Broadcasting Satellite in the United States.

ERIC Educational Resources Information Center

Kim, Haeryon

The introduction of Direct Broadcasting Satellites (DBS) in the United States sparked both government's regulatory development of domestic DBS services and the communication industry's efforts to implement a commercial DBS system. J. D. Slack's symptomatic causality and technological assessment models help to explain how these practices were…

Direct Broadcast Satellites: An Interview with Hartford Gunn.

ERIC Educational Resources Information Center

Library Hi Tech, 1984

1984-01-01

In this interview with Hartford Gunn, Vice-President of Program Development for Satellite Television Corporation (STC), the concept of direct broadcast by satellite (DBS) is explored. Allocation of radio frequencies, services provided by DBS network, home installation and purchase of dish antenna, and comparison of DBS with cable television are…

Current Topics in Deep Brain Stimulation for Parkinson Disease

PubMed Central

UMEMURA, Atsushi; OYAMA, Genko; SHIMO, Yasushi; NAKAJIMA, Madoka; NAKAJIMA, Asuka; JO, Takayuki; SEKIMOTO, Satoko; ITO, Masanobu; MITSUHASHI, Takumi; HATTORI, Nobutaka; ARAI, Hajime

2016-01-01

There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology. PMID:27349658

Role of dysphagia in evaluating Parkinson patients for subthalamic nucleus stimulation: a case report.

PubMed

Allert, Niels; Kelm, Daniela; Spottke, Annika; Coenen, Volker A

2011-09-01

In the selection of Parkinson patients for deep brain stimulation (DBS) of the subthalamic nucleus (STN) a risk-benefit-analysis is performed regarding symptoms that commonly improve and symptoms that may deteriorate. Speech is among the symptoms that may deteriorate. In contrast, the differential effects of STN-DBS on swallowing are less clear. Here, we present a Parkinson patient with dysphagia from concomitant oculo-pharyngeal muscle dystrophy successfully treated by STN-DBS. The role of dysphagia in evaluating Parkinson patients for STN-DBS is discussed.

Electrical engram: how deep brain stimulation affects memory.

PubMed

Lee, Hweeling; Fell, Jürgen; Axmacher, Nikolai

2013-11-01

Deep brain stimulation (DBS) is a surgical procedure involving implantation of a pacemaker that sends electric impulses to specific brain regions. DBS has been applied in patients with Parkinson's disease, depression, and obsessive-compulsive disorder (among others), and more recently in patients with Alzheimer's disease to improve memory functions. Current DBS approaches are based on the concept that high-frequency stimulation inhibits or excites specific brain regions. However, because DBS entails the application of repetitive electrical stimuli, it primarily exerts an effect on extracellular field-potential oscillations similar to those recorded with electroencephalography. Here, we suggest a new perspective on how DBS may ameliorate memory dysfunction: it may enhance normal electrophysiological patterns underlying long-term memory processes within the medial temporal lobe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Electric Field Comparison between Microelectrode Recording and Deep Brain Stimulation Systems—A Simulation Study

PubMed Central

Johansson, Johannes; Wårdell, Karin; Hemm, Simone

2018-01-01

The success of deep brain stimulation (DBS) relies primarily on the localization of the implanted electrode. Its final position can be chosen based on the results of intraoperative microelectrode recording (MER) and stimulation tests. The optimal position often differs from the final one selected for chronic stimulation with the DBS electrode. The aim of the study was to investigate, using finite element method (FEM) modeling and simulations, whether lead design, electrical setup, and operating modes induce differences in electric field (EF) distribution and in consequence, the clinical outcome. Finite element models of a MER system and a chronic DBS lead were developed. Simulations of the EF were performed for homogenous and patient-specific brain models to evaluate the influence of grounding (guide tube vs. stimulator case), parallel MER leads, and non-active DBS contacts. Results showed that the EF is deformed depending on the distance between the guide tube and stimulating contact. Several parallel MER leads and the presence of the non-active DBS contacts influence the EF distribution. The DBS EF volume can cover the intraoperatively produced EF, but can also extend to other anatomical areas. In conclusion, EF deformations between stimulation tests and DBS should be taken into consideration as they can alter the clinical outcome. PMID:29415442

Dried Blood Spot RNA Transcriptomes Correlate with Transcriptomes Derived from Whole Blood RNA.

PubMed

Reust, Mary J; Lee, Myung Hee; Xiang, Jenny; Zhang, Wei; Xu, Dong; Batson, Tatiana; Zhang, Tuo; Downs, Jennifer A; Dupnik, Kathryn M

2018-05-01

Obtaining RNA from clinical samples collected in resource-limited settings can be costly and challenging. The goals of this study were to 1) optimize messenger RNA extraction from dried blood spots (DBS) and 2) determine how transcriptomes generated from DBS RNA compared with RNA isolated from blood collected in Tempus tubes. We studied paired samples collected from eight adults in rural Tanzania. Venous blood was collected on Whatman 903 Protein Saver cards and in tubes with RNA preservation solution. Our optimal DBS RNA extraction used 8 × 3-mm DBS punches as the starting material, bead beater disruption at maximum speed for 60 seconds, extraction with Illustra RNAspin Mini RNA Isolation kit, and purification with Zymo RNA Concentrator kit. Spearman correlations of normalized gene counts in DBS versus whole blood ranged from 0.887 to 0.941. Bland-Altman plots did not show a trend toward over- or under-counting at any gene size. We report a method to obtain sufficient RNA from DBS to generate a transcriptome. The DBS transcriptome gene counts correlated well with whole blood transcriptome gene counts. Dried blood spots for transcriptome studies could be an option when field conditions preclude appropriate collection, storage, or transport of whole blood for RNA studies.

The temporal pattern of stimulation may be important to the mechanism of deep brain stimulation

PubMed Central

Hess, Christopher W.; Vaillancourt, David E.; Okun, Michael S.

2013-01-01

Deep brain stimulation (DBS) has emerged as an important and potentially powerful treatment option for the management of carefully selected patients with advanced Parkinson's disease (PD) who are not adequately controlled by standard medication therapy. Though considerable advances have been made, the mechanisms underlying the therapeutic effects of DBS remain unclear despite its clinical efficacy. It is now widely held that both excitation and inhibition can occur secondary to stimulation, and it is suspected that abnormal synchronized oscillations may also be important in the mechanism of DBS. Other potentially important processes, including blood flow changes, local and upstream neurogenesis, and the modulation of neurotransmitters through stimulation of bordering astrocytes are also being investigated. Recent research has suggested that the temporal pattern of DBS stimulation is also an important variable in DBS neuromodulation, yet the extent of its influence on DBS efficacy has yet to be determined. As high stimulation frequency alone does not appear to be sufficient for optimal symptom suppression, attention to stimulation pattern might lead to more effective symptom control and reduced side effects, possibly at a lower frequency. Stimulation pattern may be potentially amenable to therapeutic modulation and its role in the clinical efficacy of DBS should be addressed through further focus and research. PMID:23399890

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study.

PubMed

Cunningham, Miles G; Yadollahikhales, Golnaz; Vitaliano, Gordana; van Horne, Craig

2016-11-15

Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression. The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. Five years after initiating DBS, during a routine battery change, an apparent electrical event occurred that triggered the rapid onset of severe depression. Anti-seizure and antidepressant medications were ineffective, and the patient was offered a course of electroconvulsive therapy (ECT), which resulted in complete reversal of her depressive episode. Parkinson's syndrome can be seen after a single closed head injury event. Post-traumatic parkinsonism is responsive to DBS; however, DBS has been associated with an infrequent occurrence of dramatic disruption in mood. ECT is a therapeutic option for patients who develop intractable depressive illness associated with DBS.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

PubMed

Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

2015-04-21

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging

PubMed Central

Bot, Maarten; van den Munckhof, Pepijn; Bakay, Roy; Stebbins, Glenn; Verhagen Metman, Leo

2017-01-01

Objective To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Background Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. Methods DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. Results Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). Conclusion Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessary. PMID:28601874

Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging.

PubMed

Bot, Maarten; van den Munckhof, Pepijn; Bakay, Roy; Stebbins, Glenn; Verhagen Metman, Leo

2017-01-01

To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessary. © 2017 The Author(s) Published by S. Karger AG, Basel.

Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

PubMed Central

Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

2015-01-01

Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation. PMID:25897892

Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

PubMed

Vonberg, Isabelle; Ehlen, Felicitas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

2016-01-01

Reduced verbal fluency (VF) has been reported in patients with Parkinson's disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

Effects of replacing diet beverages with water on weight loss and weight maintenance: 18-month follow-up, randomized clinical trial.

PubMed

Madjd, A; Taylor, M A; Delavari, A; Malekzadeh, R; Macdonald, I A; Farshchi, H R

2018-04-01

Beneficial effects of replacing diet beverages (DBs) with water on weight loss, during a 24-week hypoenergetic diet were previously observed. However, it is not known whether this difference is sustained during a subsequent 12-month weight maintenance period. To evaluate effects of replacing DBs with water on body weight maintenance over a 12-month period in participants who undertook a 6-month weight loss plan. Seventy-one obese and overweight adult women (body mass index (BMI): 27-40 kg m -2 ; age: 18-50 years) who usually consumed DBs in their diet were randomly assigned to either substitute water for DBs (water group: 35) or continue drinking DBs five times per week (DBs group: 36) after their lunch for the 6-month weight loss intervention and subsequent 12-month weight maintenance program. A total of 71 participants who were randomly assigned were included in the study by using an intention-to-treat analysis. Greater additional weight loss (mean±s.d.) in the water group was observed compared with the DBs group after the 12-month follow-up period (-1.7±2.8 vs -0.1±2.7 kg, P=0.001). BMI decreased more in the water group than in the DBs group (-0.7±1 vs -0.05±1.1 kg m - 2 , P=0.003). There was also a greater reduction in fasting insulin levels (-0.5±1.4 vs -0.02±1.5 mmol l -1 , P=0.023), better improvement in homeostasis model assessment of insulin resistance (-0.2±0.4 vs -0.1±0.3, P=0.013) and a greater decrease in 2-h postprandial plasma glucose (-0.2±0.3 vs -0.1±0.3 mmol l -1 , P<0.001) in the water group compared with the DBs over the 12-month weight maintenance period. Replacement of DBs with water after the main meal in women who were regular users of DBs may cause further weight reduction during a 12-month weight maintenance program. It may also offer benefits in carbohydrate metabolism including improvement of insulin resistance over the long-term weight maintenance period.

Neurostimulation in clinical and sub-clinical eating disorders: a systematic update of the literature.

PubMed

Dalton, Bethan; Bartholdy, Savani; Campbell, Iain C; Schmidt, Ulrike

2018-01-07

Whilst psychological therapies are the main approach to treatment of eating disorders (EDs), advances in aetiological research suggest the need for the development of more targeted, brain-focused treatments. A range of neurostimulation approaches, most prominently repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS), are rapidly emerging as potential novel interventions. We have previously reviewed these techniques as potential treatments of EDs. To provide an update of the literature examining the effects of DBS, rTMS and tDCS on eating behaviours, body weight and associated symptoms in people with EDs and relevant analogue populations. Using PRISMA guidelines, we reviewed articles in PubMed, Web of Science, and PsycINFO from 1st January 2013 until 14th August 2017, to update our earlier search. Studies assessing the effects of neurostimulation techniques on eating and weight-related outcomes in people with EDs and relevant analogue populations were included. Data from both searches were combined. We included a total of 32 studies (526 participants); of these, 18 were newly identified by our update search. Whilst findings are somewhat mixed for bulimia nervosa, neurostimulation techniques have shown potential in the treatment of other EDs, in terms of reduction of ED and associated symptoms. Studies exploring cognitive, neural, and hormonal correlates of these techniques are also beginning to appear. Neurostimulation approaches show promise as treatments for EDs. As yet, large well-conducted randomised controlled trials are lacking. More information is needed about treatment targets, stimulation parameters and mechanisms of action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of the quantification of acetaminophen in plasma, cerebrospinal fluid and dried blood spots using high-performance liquid chromatography-tandem mass spectrometry

PubMed Central

Taylor, Rachel R.; Hoffman, Keith L.; Schniedewind, Björn; Clavijo, Claudia; Galinkin, Jeffrey L.; Christians, Uwe

2013-01-01

Acetaminophen (paracetamol, N-(4-hydroxyphenyl) acetamide) is one of the most commonly prescribed drugs for the management of pain in children. Quantification of acetaminophen in pre-term and term neonates and small children requires the availability of highly sensitive assays in small volume blood samples. We developed and validated an LC-MS/MS assay for the quantification of acetaminophen in human plasma, cerebro-spinal fluid (CSF) and dried blood spots (DBS). Reconstitution in water (DBS only) and addition of a protein precipitation solution containing the deuterated internal standard were the only manual steps. Extracted samples were analyzed on a Kinetex 2.6 μm PFP column using an acetonitrile/formic acid gradient. The analytes were detected in the positive multiple reaction mode. Alternatively, DBS were automatically processed using direct desorption in a sample card and preparation (SCAP) robotic autosampler in combination with online extraction. The range of reliable response in plasma and CSF was 3.05-20,000 ng/ml (r2 > 0.99) and 27.4-20,000 ng/ml (r2 > 0.99) for DBS (manual extraction and automated direct desorption). Inter-day accuracy was always within 85-115% and inter-day precision for plasma, CSF and manually extracted DBS were less than 15%. Deming regression analysis comparing 167 matching pairs of plasma and DBS samples showed a correlation coefficient of 0.98. Bland Altman analysis indicated a 26.6% positive bias in DBS, most likely reflecting the blood: plasma distribution ratio of acetaminophen. DBS are a valid matrix for acetaminophen pharmacokinetic studies. PMID:23670126

Eight-hours adaptive deep brain stimulation in patients with Parkinson disease

PubMed Central

Arlotti, Mattia; Marceglia, Sara; Foffani, Guglielmo; Volkmann, Jens; Lozano, Andres M.; Moro, Elena; Cogiamanian, Filippo; Prenassi, Marco; Bocci, Tommaso; Cortese, Francesca; Rampini, Paolo; Barbieri, Sergio

2018-01-01

Objectives To assess the feasibility and clinical efficacy of local field potentials (LFPs)–based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study. Methods We monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power. Results The beta band power correlated in both experimental sessions with the patient's clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication [3-way analysis of variance, interaction day × medication p = 0.036; 30.5 ± 3.4 vs 22.2 ± 3.3, p = 0.003]), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor “on” states compared to “off” states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias. Conclusions The main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations. Classification of evidence This study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms. PMID:29444973

A decade of emerging indications: deep brain stimulation in the United States.

PubMed

Youngerman, Brett E; Chan, Andrew K; Mikell, Charles B; McKhann, Guy M; Sheth, Sameer A

2016-08-01

OBJECTIVE Deep brain stimulation (DBS) is an emerging treatment option for an expanding set of neurological and psychiatric diseases. Despite growing enthusiasm, the patterns and implications of this rapid adoption are largely unknown. National trends in DBS surgery performed for all indications between 2002 and 2011 are reported. METHODS Using a national database of hospital discharges, admissions for DBS for 14 indications were identified and categorized as either FDA approved, humanitarian device exempt (HDE), or emerging. Trends over time were examined, differences were analyzed by univariate analyses, and outcomes were analyzed by hierarchical regression analyses. RESULTS Between 2002 and 2011, there were an estimated 30,490 discharges following DBS for approved indications, 1647 for HDE indications, and 2014 for emerging indications. The volume for HDE and emerging indications grew at 36.1% annually in comparison with 7.0% for approved indications. DBS for emerging indications occurred at hospitals with more neurosurgeons and neurologists locally, but not necessarily at those with the highest DBS caseloads. Patients treated for HDE and emerging indications were younger with lower comorbidity scores. HDE and emerging indications were associated with greater rates of reported complications, longer lengths of stay, and greater total costs. CONCLUSIONS DBS for HDE and emerging indications underwent rapid growth in the last decade, and it is not exclusively the most experienced DBS practitioners leading the charge to treat the newest indications. Surgeons may be selecting younger and healthier patients for their early experiences. Differences in reported complication rates warrant further attention and additional costs should be anticipated as surgeons gain experience with new patient populations and targets.

Voice Tremor Outcomes of Subthalamic Nucleus and Zona Incerta Deep Brain Stimulation in Patients With Parkinson Disease.

PubMed

Karlsson, Fredrik; Malinova, Elin; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik

2018-01-17

We aimed to study the effect of deep brain stimulation (DBS) in the subthalamic nucleus (STN) and caudal zona incerta (cZi) on level of perceived voice tremor in patients with Parkinson disease (PD). This is a prospective nonrandomized design with consecutive patients. Perceived voice tremor was assessed in patients with PD having received either STN-DBS (8 patients, 5 bilateral and 3 unilateral, aged 43.1-73.6 years; median = 61.2 years) or cZi-DBS (14 bilateral patients, aged 39.0-71.9 years; median = 56.6 years) 12 months before the assessment. Sustained vowels that were produced OFF and ON stimulation (with simultaneous l-DOPA medication) were assessed perceptually in terms of voice tremor by two raters on a four-point rating scale. The assessments were repeated five times per sample and rated in a blinded and randomized procedure. Three out of the 22 patients (13%) were concluded to have voice tremor OFF stimulation. Patients with PD with STN-DBS showed mild levels of perceived voice tremor OFF stimulation and a group level improvement. Patients with moderate/severe perceived voice tremor and cZi-DBS showed marked improvements, but there was no overall group effect. Six patients with cZi-DBS showed small increases in perceived voice tremor severity. STN-DBS decreased perceived voice tremor on a group level. cZi-DBS decreased perceived voice tremor in patients with PD with moderate to severe preoperative levels of the symptom. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Validation of the Use of Dried Blood Spot (DBS) Method to Assess Vitamin A Status

PubMed Central

Fallah, Elham; Peighambardoust, Seyed Hadi

2012-01-01

Background: Vitamin A deficiency is an important dietary deficiency in the world. Thus, the ne¬cessity of screening for deficient populations is obvious. This paper introduces a fast, cheap and relatively reliable method called “dried blood spot” (DBS) method in screening the deficient populations. The validity of this method for retinol measurement was investigated. Method: The “precision” and “agreement” criteria of the DBS method were assessed. The preci¬sion was calculated and compared with those of plasma using F-test. The agreement was eva¬luated using Bland-Altman plot. Results: The imprecision of retinol measurements in dried spots was not significantly different from those of the control (plasma). A good correlation coefficient (r2=0.78) was obtained for dried spots’ retinol measurements versus plasma’s retinol analysis (P < 0.01). Paired t-test showed no significant difference between the DBS and retinol methods on a group level. Imprecision of DBS measurement was acceptable, compared to that of the plasma method. The difference be¬tween these two methods was not statistically significant on a group level. Conclusion: Application of DBS standard samples, in which a part of the plasma was replaced with the artificial plasma, was shown to be a reliable calibration mean for retinol measurements in DBS samples. Retinol in dried spots was stable for 90 days. Overall, the DBS method provided a precise measurement of retinol, showing results that were comparable with the measurement of retinol in plasma. PMID:24688932

Dried Blood Spot Analysis Suitable for Therapeutic Drug Monitoring of Voriconazole, Fluconazole, and Posaconazole

PubMed Central

van der Elst, Kim C. M.; Span, Lambert F. R.; van Hateren, Kai; Vermeulen, Karin M.; van der Werf, Tjip S.; Greijdanus, Ben; Kosterink, Jos G. W.; Uges, Donald R. A.

2013-01-01

Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P = 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling. PMID:23896473

Turning off artistic ability: the influence of left DBS in art production.

PubMed

Drago, V; Foster, P S; Okun, M S; Cosentino, F I I; Conigliaro, R; Haq, I; Sudhyadhom, A; Skidmore, F M; Heilman, K M

2009-06-15

The influence of Parkinson's disease (PD) as well as deep brain stimulation (DBS) on visual-artistic production of people who have been artists is unclear. We systematically assessed the artistic-creative productions of a patient with PD who was referred to us for management of a left subthalamic region (STN) DBS. The patient was an artist before her disease started, permitting us to analyze changes in her artistic-creative production over the course of the illness and during her treatment with DBS. We collected her paintings from four time periods: Time 1 (Early Pre-Presymptomatic), Time 2 (Later Presymptomatic), Time 3 (Symptomatic), and Time 4 (DBS Symptomatic). A total of 59 paintings were submitted to a panel of judges, who rated the paintings on 6 different artistic qualities including: aesthetics, closure, evocative impact, novelty, representation, technique. Aesthetics and evocative impact significantly declined from Time 2 to Time 4. Representation and technique indicated a curvilinear relationship, with initial improvement from Time 1 to Time 2 followed by a decline from Time 2 to Time 4. These results suggest that left STN/SNR-DBS impacted artistic performances in our patient. The reason for these alterations is not known, but it might be that alterations of left hemisphere functions induce a hemispheric bias reducing the influence the right hemisphere which is important for artistic creativity. The left hemisphere itself plays a critical role in artistic creativity and DBS might have altered left hemisphere functions or altered the mesolimbic system which might have also influenced creativity. Future studies will be required to learn how PD and DBS influence creativity.

47 CFR 101.1440 - MVDDS protection of DBS.

Code of Federal Regulations, 2014 CFR

2014-10-01

... licensees are notified of a potential MVDDS site in paragraph (d)(1) of this section, the DBS licensees are... FIXED MICROWAVE SERVICES Multichannel Video Distribution and Data Service Rules for the 12.2-12.7 GHz Band § 101.1440 MVDDS protection of DBS. (a) An MVDDS licensee shall not begin operation unless it can...

47 CFR 101.1440 - MVDDS protection of DBS.

Code of Federal Regulations, 2012 CFR

2012-10-01

... licensees are notified of a potential MVDDS site in paragraph (d)(1) of this section, the DBS licensees are... FIXED MICROWAVE SERVICES Multichannel Video Distribution and Data Service Rules for the 12.2-12.7 GHz Band § 101.1440 MVDDS protection of DBS. (a) An MVDDS licensee shall not begin operation unless it can...

47 CFR 101.1440 - MVDDS protection of DBS.

Code of Federal Regulations, 2013 CFR

2013-10-01

... licensees are notified of a potential MVDDS site in paragraph (d)(1) of this section, the DBS licensees are... FIXED MICROWAVE SERVICES Multichannel Video Distribution and Data Service Rules for the 12.2-12.7 GHz Band § 101.1440 MVDDS protection of DBS. (a) An MVDDS licensee shall not begin operation unless it can...

Laser cutting eliminates nucleic acid cross-contamination in dried-blood-spot processing.

PubMed

Murphy, Sean C; Daza, Glenda; Chang, Ming; Coombs, Robert

2012-12-01

Dried blood spots (DBS) are useful for molecular assays but are prone to false positives from cross-contamination. In our malaria DBS assay, cross-contamination was encountered despite cleaning techniques suitable for HIV-1. We therefore developed a contact-free laser cutting system that effectively eliminated cross-contamination during DBS processing.

Shaking Up the Debate: Ensuring the Ethical Use of DBS Intervention Criteria for Mid-Stage Parkinson's Patients.

PubMed

Eijkholt, Marleen; Cabrera, Laura Y; Ramirez-Zamora, Adolfo; Pilitsis, Julie G

2017-07-01

Deep brain stimulation (DBS) is a well-established treatment for the management of severe motor fluctuations in advanced Parkinson's disease (PD). Until recently, device regulation, medical, and insurance practices limited DBS to patients with advanced stages of PD. In February 2016 this changed, however, when the US Food and Drug Administration (FDA) granted formal approval for the use of brain stimulator in mid-stage PD patients. In this article, we examine whether DBS in mid-stage PD can be ethically justified beyond the FDA approval. We scrutinize the current risk-benefit profile, the costs-benefit profile, and the capacity for informed consent requirement, to ask if use of subthalamic nucleus (STN) in mid-stage DBS is ethically appropriate. We propose that mid-stage DBS decisions could be appropriate under a shared decision-making model, which embraces a broad quality of life perspective. Although it might be too premature to know how the FDA decision will affect medical and insurance practices, we conclude by arguing that revisions to persisting guidelines seems justified both on scientific and ethical grounds. © 2017 International Neuromodulation Society.

Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases.

PubMed

Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekaj, Edvin; Villani, Flavio; Leone, Massimo; Gambini, Orsola; Broggi, Giovanni

2012-12-01

Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.

Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

PubMed Central

Deeb, Wissam; Giordano, James J.; Rossi, Peter J.; Mogilner, Alon Y.; Gunduz, Aysegul; Judy, Jack W.; Klassen, Bryan T.; Butson, Christopher R.; Van Horne, Craig; Deny, Damiaan; Dougherty, Darin D.; Rowell, David; Gerhardt, Greg A.; Smith, Gwenn S.; Ponce, Francisco A.; Walker, Harrison C.; Bronte-Stewart, Helen M.; Mayberg, Helen S.; Chizeck, Howard J.; Langevin, Jean-Philippe; Volkmann, Jens; Ostrem, Jill L.; Shute, Jonathan B.; Jimenez-Shahed, Joohi; Foote, Kelly D.; Wagle Shukla, Aparna; Rossi, Marvin A.; Oh, Michael; Pourfar, Michael; Rosenberg, Paul B.; Silburn, Peter A.; de Hemptine, Coralie; Starr, Philip A.; Denison, Timothy; Akbar, Umer; Grill, Warren M.; Okun, Michael S.

2016-01-01

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field. PMID:27920671

A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

PubMed Central

Gong, Cihun-Siyong Alex; Lai, Hsin-Yi; Huang, Sy-Han; Lo, Yu-Chun; Lee, Nicole; Chen, Pin-Yuan; Tu, Po-Hsun; Yang, Chia-Yen; Lin, James Chang-Chieh; Chen, You-Yin

2015-01-01

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design. PMID:26029954

Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

PubMed

Segar, David J; Chodakiewitz, Yosef G; Torabi, Radmehr; Cosgrove, G Rees

2015-06-01

Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

Three-dimensional brain MRI for DBS patients within ultra-low radiofrequency power limits.

PubMed

Sarkar, Subhendra N; Papavassiliou, Efstathios; Hackney, David B; Alsop, David C; Shih, Ludy C; Madhuranthakam, Ananth J; Busse, Reed F; La Ruche, Susan; Bhadelia, Rafeeque A

2014-04-01

For patients with deep brain stimulators (DBS), local absorbed radiofrequency (RF) power is unknown and is much higher than what the system estimates. We developed a comprehensive, high-quality brain magnetic resonance imaging (MRI) protocol for DBS patients utilizing three-dimensional (3D) magnetic resonance sequences at very low RF power. Six patients with DBS were imaged (10 sessions) using a transmit/receive head coil at 1.5 Tesla with modified 3D sequences within ultra-low specific absorption rate (SAR) limits (0.1 W/kg) using T2 , fast fluid-attenuated inversion recovery (FLAIR) and T1 -weighted image contrast. Tissue signal and tissue contrast from the low-SAR images were subjectively and objectively compared with routine clinical images of six age-matched controls. Low-SAR images of DBS patients demonstrated tissue contrast comparable to high-SAR images and were of diagnostic quality except for slightly reduced signal. Although preliminary, we demonstrated diagnostic quality brain MRI with optimized, volumetric sequences in DBS patients within very conservative RF safety guidelines offering a greater safety margin. © 2014 International Parkinson and Movement Disorder Society.

Application of DBS sampling in combination with LC-MS/MS for pharmacokinetic evaluation of a compound with species-specific blood-to-plasma partitioning.

PubMed

Xu, Guifen; Chen, Jiyun S; Phadnis, Ruta; Huang, Tom; Uyeda, Craig; Soto, Marcus; Stouch, Brian; Wells, Mary C; James, Christopher A; Carlson, Timothy J

2012-08-01

Dried blood spot (DBS) sampling in combination with LC-MS/MS has been used increasingly in drug discovery for quantitative analysis to support pharmacokinetic (PK) studies. In this study, we assessed the effect of blood-to-plasma (B:P) partitioning on the bioanalytical performance and PK data acquired by DBS for a compound AMG-1 with species and concentration-dependent B:P ratio. B:P partitioning did not adversely affect bioanalytical performance of DBS for AMG-1. For rat, (B:P ratio of 0.63), PK profiles from DBS and plasma methods were comparable. For dog, concentration-dependence of B:P ratio was observed both in vivo and in vitro. Additional studies demonstrated concentration-dependence of the compound's unbound fraction in plasma, which may contribute to the concentration-dependence of the B:P ratio. DBS is a promising sampling technique for preclinical pharmacokinetic studies. For compounds with high B:P ratio, caution needs to be applied for data comparison and interpretation between matrices.

Uncovering the mechanism(s) of deep brain stimulation

NASA Astrophysics Data System (ADS)

Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

2005-01-01

Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease

PubMed Central

de Hemptinne, Coralie; Swann, Nicole; Ostrem, Jill L.; Ryapolova-Webb, Elena S.; Luciano, Marta San; Galifianakis, Nicholas; Starr, Philip A.

2015-01-01

Deep brain stimulation (DBS) is increasingly applied to the treatment of brain disorders, but its mechanism of action remains unknown. Here, we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the β rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive β phase locking of motor cortex neurons. PMID:25867121

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification

PubMed Central

Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-01-01

Abstract The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS. Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined. A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was <0.5 log cps/mL with all 3 assays but >25% of the specimens differed by >0.5 log cps/mL. All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1). The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens. PMID:27902602

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification: A laboratory assessment of 3 commercial assays.

PubMed

Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-11-01

The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS.Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined.A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was <0.5 log cps/mL with all 3 assays but >25% of the specimens differed by >0.5 log cps/mL.All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1).The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens.

SU-F-T-519: Is Geometry Based Setup Sufficient for All of the Head and Neck Treatment Cases?: A Feasibility Study Towards the Dose Based Setup

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S; Chen, S; Zhang, B

Purpose: This study compares the geometric-based setup (GBS) which is currently used in the clinic to a novel concept of dose-based setup (DBS) of head and neck (H&N) patients using cone beam CT (CBCT) of the day; and evaluates the clinical advantages. Methods: Ten H&N patients who underwent re-simulation and re-plan due to noticeable anatomic changes during the course of the treatments were retrospectively reviewed on dosimetric changes in the assumption of no plan modification was performed. RayStation planning system (RaySearch Laboratories AB, Sweden) was used to match (ROI fusion module) between prescribed isodoseline (IDL) in the CBCT imported alongmore » with ROIs from re-planned CT and the IDL of original plan (Dose-based setup: DBS). Then, the CBCT plan based on daily setup using the GBS (previously used for a patient) and the DBS CBCT plan recalculated in RayStation compared against the original CT-sim plan. Results: Most of patients’ tumor coverage and OAR doses got generally worsen when the CBCT plans were compared with original CT-sim plan with GBS. However, when DBS intervened, the OAR dose and tumor coverage was better than the GBS. For example, one of patients’ daily average doses of right parotid and oral cavity increased to 26% and 36%, respectively from the original plan to the GBS planning. However, it only increased by 13% and 24%, respectively with DBS. GTV D95 coverage also decreased by 16% with GBS, but only 2% decreased with DBS. Conclusion: DBS method is superior to GBS to prevent any abrupt dose changes to OARs as well as PTV/CTV or GTV at least for some H&N cases. Since it is not known when the DBS is beneficial to the GBS, a system which enables the on-line DBS may be helpful for better treatment of H&N.« less

Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation.

PubMed

Pham, Uyen Ha Gia; Andersson, Stein; Toft, Mathias; Pripp, Are Hugo; Konglund, Ane Eidahl; Dietrichs, Espen; Malt, Ulrik Fredrik; Skogseid, Inger Marie; Haraldsen, Ira Ronit Hebolt; Solbakk, Anne-Kristin

2015-01-01

Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS.

Changing of the guard: reducing infection when replacing neural pacemakers.

PubMed

Pepper, Joshua; Meliak, Lara; Akram, Harith; Hyam, Jonathan; Milabo, Catherine; Candelario, Joseph; Foltynie, Thomas; Limousin, Patricia; Curtis, Carmel; Hariz, Marwan; Zrinzo, Ludvic

2017-04-01

OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ± 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.

European clinical guidelines for Tourette syndrome and other tic disorders. Part IV: deep brain stimulation.

PubMed

Müller-Vahl, Kirsten R; Cath, Danielle C; Cavanna, Andrea E; Dehning, Sandra; Porta, Mauro; Robertson, Mary M; Visser-Vandewalle, Veerle

2011-04-01

Ten years ago deep brain stimulation (DBS) has been introduced as an alternative and promising treatment option for patients suffering from severe Tourette syndrome (TS). It seemed timely to develop a European guideline on DBS by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). For a narrative review a systematic literature search was conducted and expert opinions of the guidelines group contributed also to the suggestions. Of 63 patients reported so far in the literature 59 had a beneficial outcome following DBS with moderate to marked tic improvement. However, randomized controlled studies including a larger number of patients are still lacking. Although persistent serious adverse effects (AEs) have hardly been reported, surgery-related (e.g., bleeding, infection) as well as stimulation-related AEs (e.g., sedation, anxiety, altered mood, changes in sexual function) may occur. At present time, DBS in TS is still in its infancy. Due to both different legality and practical facilities in different European countries these guidelines, therefore, have to be understood as recommendations of experts. However, among the ESSTS working group on DBS in TS there is general agreement that, at present time, DBS should only be used in adult, treatment resistant, and severely affected patients. It is highly recommended to perform DBS in the context of controlled trials.

Comparing identified and statistically significant lipids and polar metabolites in 15-year old serum and dried blood spot samples for longitudinal studies: Comparing lipids and metabolites in serum and DBS samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kyle, Jennifer E.; Casey, Cameron P.; Stratton, Kelly G.

The use of dried blood spots (DBS) has many advantages over traditional plasma and serum samples such as smaller blood volume required, storage at room temperature, and ability for sampling in remote locations. However, understanding the robustness of different analytes in DBS samples is essential, especially in older samples collected for longitudinal studies. Here we analyzed DBS samples collected in 2000-2001 and stored at room temperature and compared them to matched serum samples stored at -80°C to determine if they could be effectively used as specific time points in a longitudinal study following metabolic disease. Four hundred small molecules weremore » identified in both the serum and DBS samples using gas chromatograph-mass spectrometry (GC-MS), liquid chromatography-MS (LC-MS) and LC-ion mobility spectrometry-MS (LC-IMS-MS). The identified polar metabolites overlapped well between the sample types, though only one statistically significant polar metabolite in a case-control study was conserved, indicating degradation occurs in the DBS samples affecting quantitation. Differences in the lipid identifications indicated that some oxidation occurs in the DBS samples. However, thirty-six statistically significant lipids correlated in both sample types indicating that lipid quantitation was more stable across the sample types.« less

Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients.

PubMed

Wagenbreth, Caroline; Zaehle, Tino; Galazky, Imke; Voges, Jürgen; Guitart-Masip, Marc; Heinze, Hans-Jochen; Düzel, Emrah

2015-06-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC.

Chronic Deep Brain Stimulation of the Hypothalamic Nucleus in Wistar Rats Alters Circulatory Levels of Corticosterone and Proinflammatory Cytokines

PubMed Central

Calleja-Castillo, Juan Manuel; De La Cruz-Aguilera, Dora Luz; Manjarrez, Joaquín; Velasco-Velázquez, Marco Antonio; Morales-Espinoza, Gabriel; Moreno-Aguilar, Julia; Hernández, Maria Eugenia; Aguirre-Cruz, Lucinda

2013-01-01

Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-α (120%; P < 0.01) and IFN-γ (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1β (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication. PMID:24235973

Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation.

PubMed

Williams, Amy E; Arzola, Gladys Marina; Strutt, Adriana M; Simpson, Richard; Jankovic, Joseph; York, Michele K

2011-06-01

Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson's disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25-30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

47 CFR 73.756 - System specifications for double-sideband (DBS) modulated emissions in the HF broadcasting service.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false System specifications for double-sideband (DBS... Stations § 73.756 System specifications for double-sideband (DBS) modulated emissions in the HF... processing. If audio-frequency signal processing is used, the dynamic range of the modulating signal shall be...

Laser Cutting Eliminates Nucleic Acid Cross-Contamination in Dried-Blood-Spot Processing

PubMed Central

Daza, Glenda; Chang, Ming; Coombs, Robert

2012-01-01

Dried blood spots (DBS) are useful for molecular assays but are prone to false positives from cross-contamination. In our malaria DBS assay, cross-contamination was encountered despite cleaning techniques suitable for HIV-1. We therefore developed a contact-free laser cutting system that effectively eliminated cross-contamination during DBS processing. PMID:23052309

A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson’s disease—a pilot study

NASA Astrophysics Data System (ADS)

Gmel, Gerrit E.; Hamilton, Tara J.; Obradovic, Milan; Gorman, Robert B.; Single, Peter S.; Chenery, Helen J.; Coyne, Terry; Silburn, Peter A.; Parker, John L.

2015-12-01

Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson’s disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

Estrogen Regulation of Duodenal Bicarbonate Secretion and Sex-Specific Protection of Human Duodenum

PubMed Central

Tuo, Biguang; Wen, Guorong; Wei, Jinqi; Liu, Xuemei; Wang, Xue; Zhang, Yalin; Wu, Huichao; Dong, Xiao; Chow, Jimmy Y.C.; Vallon, Volker; Dong, Hui

2011-01-01

BACKGROUND & AIMS The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. METHODS We performed an epidemiological study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. RESULTS Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20–49 years), who were 3.91–5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to ≤1.32-fold among subjects 60 years or older. Premenopausal (20–29 years), but not post-menopausal (60–69 years) women, had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20–29 years) were significantly higher than in post-menopausal women (60–69 years), whereas there were no significant differences in basal or acid-stimulated DBS between men that were 20–29 years old or 60–69 years old. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors- and - were detected on plasma membrane and in cytosol of human duodenal epithelial cells. CONCLUSIONS Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in prevalence of duodenal ulcer. PMID:21699784

Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum.

PubMed

Tuo, Biguang; Wen, Guorong; Wei, Jinqi; Liu, Xuemei; Wang, Xue; Zhang, Yalin; Wu, Huichao; Dong, Xiao; Chow, Jimmy Y C; Vallon, Volker; Dong, Hui

2011-09-01

The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. We performed an epidemiologic study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen-receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20-49 y), who were 3.91- to 5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to 1.32-fold or less among subjects aged 60 years or older. Premenopausal (20-29 y), but not postmenopausal (60-69 y), women had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20-29 y) were significantly higher than in postmenopausal women (60-69 y), whereas there were no significant differences in basal or acid-stimulated DBS between men who were aged 20-29 years or 60-69 years. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors α and β were detected on plasma membranes and in the cytosol of human duodenal epithelial cells. Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in the prevalence of duodenal ulcer. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

PubMed

Katz, Maya; Luciano, Marta San; Carlson, Kimberly; Luo, Ping; Marks, William J; Larson, Paul S; Starr, Philip A; Follett, Kenneth A; Weaver, Frances M; Stern, Matthew B; Reda, Domenic J; Ostrem, Jill L

2015-04-01

The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. We classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. TD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 ± 12.2 vs 21.7 ± 11.2 vs 16.3 ± 13.8, p = 0.001). Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation. © 2015 American Neurological Association.

Rapid DNA extraction protocol for detection of alpha-1 antitrypsin deficiency from dried blood spots by real-time PCR.

PubMed

Struniawski, R; Szpechcinski, A; Poplawska, B; Skronski, M; Chorostowska-Wynimko, J

2013-01-01

The dried blood spot (DBS) specimens have been successfully employed for the large-scale diagnostics of α1-antitrypsin (AAT) deficiency as an easy to collect and transport alternative to plasma/serum. In the present study we propose a fast, efficient, and cost effective protocol of DNA extraction from dried blood spot (DBS) samples that provides sufficient quantity and quality of DNA and effectively eliminates any natural PCR inhibitors, allowing for successful AAT genotyping by real-time PCR and direct sequencing. DNA extracted from 84 DBS samples from chronic obstructive pulmonary disease patients was genotyped for AAT deficiency variants by real-time PCR. The results of DBS AAT genotyping were validated by serum IEF phenotyping and AAT concentration measurement. The proposed protocol allowed successful DNA extraction from all analyzed DBS samples. Both quantity and quality of DNA were sufficient for further real-time PCR and, if necessary, for genetic sequence analysis. A 100% concordance between AAT DBS genotypes and serum phenotypes in positive detection of two major deficiency S- and Z- alleles was achieved. Both assays, DBS AAT genotyping by real-time PCR and serum AAT phenotyping by IEF, positively identified PI*S and PI*Z allele in 8 out of the 84 (9.5%) and 16 out of 84 (19.0%) patients, respectively. In conclusion, the proposed protocol noticeably reduces the costs and the hand-on-time of DBS samples preparation providing genomic DNA of sufficient quantity and quality for further real-time PCR or genetic sequence analysis. Consequently, it is ideally suited for large-scale AAT deficiency screening programs and should be method of choice.

Technical Stability and Biological Variability in MicroRNAs from Dried Blood Spots: A Lung Cancer Therapy-Monitoring Showcase.

PubMed

Kahraman, Mustafa; Laufer, Thomas; Backes, Christina; Schrörs, Hannah; Fehlmann, Tobias; Ludwig, Nicole; Kohlhaas, Jochen; Meese, Eckart; Wehler, Thomas; Bals, Robert; Keller, Andreas

2017-09-01

Different work flows have been proposed to use miRNAs as blood-borne biomarkers. In particular, the method used for collecting blood from patients can considerably influence the diagnostic results. We explored whether dried blood spots (DBSs) facilitate stable miRNA measurements and compared its technical stability with biological variability. First, we tested the stability of DBS samples by generating from 1 person 18 whole-genome-wide miRNA profiles of DBS samples that were exposed to different temperature and humidity conditions. Second, we investigated technical reproducibility by performing 7 replicates of DBS again from 1 person. Third, we investigated DBS samples from 53 patients with lung cancer undergoing different therapies. Across these 3 stages, 108 genome-wide miRNA profiles from DBS were generated and evaluated biostatistically. In the stability analysis, we observed that temperature and humidity had an overall limited influence on the miRNomes (average correlation between the different conditions of 0.993). Usage of a silica gel slightly diminished DBS' technical reproducibility. The 7 technical replicates had an average correlation of 0.996. The correlation with whole-blood PAXGene miRNomes of the same individual was remarkable (correlation of 0.88). Finally, evaluation of the samples from the 53 patients with lung cancer exposed to different therapies showed that the biological variations exceeded the technical variability significantly ( P < 0.0001), yielding 51 dysregulated miRNAs. We present a stable work flow for profiling of whole miRNomes on the basis of samples collected from DBS. Biological variations exceeded technical variations significantly. DBS-based miRNA profiles will potentially further the translational character of miRNA biomarker studies. © 2017 American Association for Clinical Chemistry.

Comparison of the quantification of acetaminophen in plasma, cerebrospinal fluid and dried blood spots using high-performance liquid chromatography-tandem mass spectrometry.

PubMed

Taylor, Rachel R; Hoffman, Keith L; Schniedewind, Björn; Clavijo, Claudia; Galinkin, Jeffrey L; Christians, Uwe

2013-09-01

Acetaminophen (paracetamol, N-(4-hydroxyphenyl) acetamide) is one of the most commonly prescribed drugs for the management of pain in children. Quantification of acetaminophen in pre-term and term neonates and small children requires the availability of highly sensitive assays in small volume blood samples. We developed and validated an LC-MS/MS assay for the quantification of acetaminophen in human plasma, cerebro-spinal fluid (CSF) and dried blood spots (DBS). Reconstitution in water (DBS only) and addition of a protein precipitation solution containing the deuterated internal standard were the only manual steps. Extracted samples were analyzed on a Kinetex 2.6 μm PFP column using an acetonitrile/formic acid gradient. The analytes were detected in the positive multiple reaction mode. Alternatively, DBS were automatically processed using direct desorption in a sample card and preparation (SCAP) robotic autosampler in combination with online extraction. The range of reliable response in plasma and CSF was 3.05-20,000 ng/ml (r(2)>0.99) and 27.4-20,000 ng/ml (r(2)>0.99) for DBS (manual extraction and automated direct desorption). Inter-day accuracy was always within 85-115% and inter-day precision for plasma, CSF and manually extracted DBS were less than 15%. Deming regression analysis comparing 167 matching pairs of plasma and DBS samples showed a correlation coefficient of 0.98. Bland Altman analysis indicated a 26.6% positive bias in DBS, most likely reflecting the blood: plasma distribution ratio of acetaminophen. DBS are a valid matrix for acetaminophen pharmacokinetic studies. Copyright © 2013 Elsevier B.V. All rights reserved.

The Impact of Deep Brain Stimulation on the Quality of Life and Swallowing in Individuals with Parkinson's Disease

PubMed Central

Olchik, Maira Rozenfel; Ghisi, Marciéle; Ayres, Annelise; Schuh, Arthur Francisco Shumacher; Oppitz, Paulo Petry; Rieder, Carlos Roberto de Mello

2018-01-01

Introduction  Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD). However, there is little evidence regarding the effect of DBS on dysphagia. Objective  To assess the swallowing and quality of life of individuals with PD before and after DBS surgery. Methods  Our sample consisted of people who had undergone DBS surgery in a referral hospital in the state of Rio Grande do Sul, Brazil. The inclusion criteria were a diagnosis of PD and having undergone DBS surgery. A cognitive screening, through a questionnaire about depression and quality of life, was conducted. Evaluations of each patient's swallowing were performed before and after surgery. The assessment consisted of anamnesis, clinical assessment, the Functional Oral Intake Scale, clinical evaluation of swallowing, and the Hoehn and Yahr scale. Results  The sample included 10 individuals, all male, with a mean age of 57.3 years (±4.7), a mean disease duration of 13.0 years (±2.4), and mean level education of 8.1 years (±4.0). In the clinical evaluation of the swallowing, a significant improvement after DBS was not observed. However, little changes in the signs and symptoms of dysphagia that had a positive impact on the quality of life were observed. Furthermore, there was no relation between the patients' motor subtype and swallowing pre- and post-DBS. Conclusion  There was an improvement in the quality of life of the patients after DBS. However, the improvement in the clinical signs and symptoms of dysphagia did not cause an overall improvement in the swallowing function. PMID:29619099

Deep Brain Stimulation to Alleviate Freezing of Gait and Cognitive Dysfunction in Parkinson's Disease: Update on Current Research and Future Perspectives.

PubMed

Huang, Chuyi; Chu, Heling; Zhang, Yan; Wang, Xiaoping

2018-01-01

Freezing of gait (FOG) is a gait disorder featured by recurrent episodes of temporary gait halting and mainly found in advanced Parkinson's disease (PD). FOG has a severe impact on the quality of life of patients with PD. The pathogenesis of FOG is unclear and considered to be related to several brain areas and neural circuits. Its close connection with cognitive disorder has been proposed and some researchers explain the pathogenesis using the cognitive model theory. FOG occurs concurrently with cognitive disorder in some PD patients, who are poorly responsive to medication therapy. Deep brain stimulation (DBS) proves effective for FOG in PD patients. Cognitive impairment plays a role in the formation of FOG. Therefore, if DBS works by improving the cognitive function, both two challenging conditions can be ameliorated by DBS. We reviewed the clinical studies related to DBS for FOG in PD patients over the past decade. In spite of the varying stimulation parameters used in different studies, DBS of either subthalamic nucleus (STN) or pedunculopontine nucleus (PPN) alone or in combination can improve the symptoms of FOG. Moreover, the treatment efficacy can last for 1-2 years and DBS is generally safe. Although few studies have been conducted concerning the use of DBS for cognitive disorder in FOG patients, the existing studies seem to indicate that PPN is a potential therapeutic target to both FOG and cognitive disorder. However, most of the studies have a small sample size and involve sporadic cases, so it remains uncertain which nucleus is the optimal target of stimulation. Prospective clinical trials with a larger sample size are needed to systematically assess the efficacy of DBS for FOG and cognitive disorder.

In Parkinson's disease STN stimulation enhances responsiveness of movement initiation speed to high reward value.

PubMed

Kojovic, Maja; Higgins, Andrea; Jahanshahi, Marjan

2016-08-01

The subthalamic nucleus (STN) is part of the motor, associative, and limbic cortico-striatal circuits through which it can influence a range of behaviours, with preclinical and clinical evidence suggesting that the STN is involved in motivational modulation of behaviour. In the present study, we investigated if in Parkinson's disease (PD) motivational modulation of movement speed is altered by deep brain stimulation (DBS) of the STN (STN-DBS). We studied the effect of monetary incentive on speed of movement initiation and execution in a computer-based simple reaction time task in 10 operated patients with Parkinson's disease using a STN DBS ON/OFF design and also in 11 healthy participants. Prospect of reward improved speed of movement initiation in PD patients both with STN-DBS ON and OFF. However, only with STN-DBS ON, the patients showed greater speeding of initiation time with higher reward magnitude, suggesting enhanced responsivity to higher reward value. Also, on the rewarded trials, PD patients ON stimulation made more anticipation errors than on unrewarded trials, reflecting a propensity to impulsive responses triggered by prospect of reward by subthalamic stimulation. The motivational modulation of movement speed was preserved and enhanced in PD with STN-DBS. Motivational modulation of movement speed in PD is maintained with STN-DBS, with STN stimulation having a further energizing effect on movement initiation in response to greater incentive value. Our results suggest that STN plays a role in integrating motivational influences into motor action, which may explain some previous reports of STN-DBS induced impulsivity with increased motivational salience of stimuli. Copyright © 2016. Published by Elsevier Ltd.

Complications of deep brain stimulation: a collective review.

PubMed

Chan, Danny T M; Zhu, Xian Lun; Yeung, Jonas H M; Mok, Vincent C T; Wong, Edith; Lau, Clara; Wong, Rosanna; Lau, Christine; Poon, Wai S

2009-10-01

Since the first deep brain stimulation (DBS) performed for movement disorder more than a decade ago, DBS has become a standard operation for advanced Parkinson's disease. Its indications are expanding to areas of dystonia, psychiatric conditions and refractory epilepsy. Additionally, a new set of DBS-related complications have arisen. Many teams found a slow learning curve from this complication-prone operation. We would like to investigate complications arising from 100 DBS electrode insertions and its prevention. We performed an audit in all DBS patients for operation-related complications in our centre from 1997 to 2008. Complications were classified into operation-related, hardware-related and stimulation-related. Operation-related complications included intracranial haemorrhages and electrode malposition. Hardware-related complications included fracture of electrodes, electrode migration, infection and erosion. Stimulation-related complications included sensorimotor conditions, psychiatric conditions and life-threatening conditions. From 1997 to the end of 2008, 100 DBS electrodes were inserted in 55 patients for movement disorders, mostly for Parkinsons disease (50 patients). There was one symptomatic cerebral haemorrhage (1%) and two electrode malpositions (2%). Meticulous surgical planning, use of microdriver and a reliable electrode anchorage device would minimise this group of complications. There were two electrode fractures, one electrode migration and one pulse-generator infection which contributed to the hardware-related complication rate of 5%. There were no sensorimotor or life-threatening complications in our group. However, three patients suffered from reversible psychiatric symptoms after DBS. DBS is, on the one hand, an effective surgical treatment for movement disorders. On the other hand, it is a complication-prone operation. A dedicated "Movement Disorder Team" consisting of neurologists, neurophysiologists, functional neurosurgeons, neuropsychologists and nursing specialists is essential. Liaison among team members in peri-operative periods and postoperative care is the key to avoiding complications and having a successful patient outcome.

Degree-based statistic and center persistency for brain connectivity analysis.

PubMed

Yoo, Kwangsun; Lee, Peter; Chung, Moo K; Sohn, William S; Chung, Sun Ju; Na, Duk L; Ju, Daheen; Jeong, Yong

2017-01-01

Brain connectivity analyses have been widely performed to investigate the organization and functioning of the brain, or to observe changes in neurological or psychiatric conditions. However, connectivity analysis inevitably introduces the problem of mass-univariate hypothesis testing. Although, several cluster-wise correction methods have been suggested to address this problem and shown to provide high sensitivity, these approaches fundamentally have two drawbacks: the lack of spatial specificity (localization power) and the arbitrariness of an initial cluster-forming threshold. In this study, we propose a novel method, degree-based statistic (DBS), performing cluster-wise inference. DBS is designed to overcome the above-mentioned two shortcomings. From a network perspective, a few brain regions are of critical importance and considered to play pivotal roles in network integration. Regarding this notion, DBS defines a cluster as a set of edges of which one ending node is shared. This definition enables the efficient detection of clusters and their center nodes. Furthermore, a new measure of a cluster, center persistency (CP) was introduced. The efficiency of DBS with a known "ground truth" simulation was demonstrated. Then they applied DBS to two experimental datasets and showed that DBS successfully detects the persistent clusters. In conclusion, by adopting a graph theoretical concept of degrees and borrowing the concept of persistence from algebraic topology, DBS could sensitively identify clusters with centric nodes that would play pivotal roles in an effect of interest. DBS is potentially widely applicable to variable cognitive or clinical situations and allows us to obtain statistically reliable and easily interpretable results. Hum Brain Mapp 38:165-181, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism

PubMed Central

Whiting, Donald M.; Tomycz, Nestor D.; Bailes, Julian; De Jonge, Lilian; Lecoultre, Virgile; Wilent, Bryan; Alcindor, Dunbar; Prostko, E. Richard; Cheng, Boyle C.; Angle, Cynthia; Cantella, Diane; Whiting, Benjamin B.; Mizes, J. Scott; Finnis, Kirk W.; Ravussin, Eric; Oh, Michael Y.

2017-01-01

Object Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans. Methods Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, under-went bilateral implantation of LHA DBS electrodes as part of an institutional review board– and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism. Results No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30–39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber. Conclusions Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first “proof of principle” for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy. PMID:23560573

High-frequency stimulation of the subthalamic nucleus restores neural and behavioral functions during reaction time task in a rat model of Parkinson's disease.

PubMed

Li, Xiang-Hong; Wang, Jin-Yan; Gao, Ge; Chang, Jing-Yu; Woodward, Donald J; Luo, Fei

2010-05-15

Deep brain stimulation (DBS) has been used in the clinic to treat Parkinson's disease (PD) and other neuropsychiatric disorders. Our previous work has shown that DBS in the subthalamic nucleus (STN) can improve major motor deficits, and induce a variety of neural responses in rats with unilateral dopamine (DA) lesions. In the present study, we examined the effect of STN DBS on reaction time (RT) performance and parallel changes in neural activity in the cortico-basal ganglia regions of partially bilateral DA- lesioned rats. We recorded neural activity with a multiple-channel single-unit electrode system in the primary motor cortex (MI), the STN, and the substantia nigra pars reticulata (SNr) during RT test. RT performance was severely impaired following bilateral injection of 6-OHDA into the dorsolateral part of the striatum. In parallel with such behavioral impairments, the number of responsive neurons to different behavioral events was remarkably decreased after DA lesion. Bilateral STN DBS improved RT performance in 6-OHDA lesioned rats, and restored operational behavior-related neural responses in cortico-basal ganglia regions. These behavioral and electrophysiological effects of DBS lasted nearly an hour after DBS termination. These results demonstrate that a partial DA lesion-induced impairment of RT performance is associated with changes in neural activity in the cortico-basal ganglia circuit. Furthermore, STN DBS can reverse changes in behavior and neural activity caused by partial DA depletion. The observed long-lasting beneficial effect of STN DBS suggests the involvement of the mechanism of neural plasticity in modulating cortico-basal ganglia circuits. (c) 2009 Wiley-Liss, Inc.

Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates

PubMed Central

Ryou, Jae-Wook; Wei, Xuefeng F.; Butson, Christopher R.; Schiff, Nicholas D.; Purpura, Keith P.

2016-01-01

The central thalamus (CT) is a key component of the brain-wide network underlying arousal regulation and sensory-motor integration during wakefulness in the mammalian brain. Dysfunction of the CT, typically a result of severe brain injury (SBI), leads to long-lasting impairments in arousal regulation and subsequent deficits in cognition. Central thalamic deep brain stimulation (CT-DBS) is proposed as a therapy to reestablish and maintain arousal regulation to improve cognition in select SBI patients. However, a mechanistic understanding of CT-DBS and an optimal method of implementing this promising therapy are unknown. Here we demonstrate in two healthy nonhuman primates (NHPs), Macaca mulatta, that location-specific CT-DBS improves performance in visuomotor tasks and is associated with physiological effects consistent with enhancement of endogenous arousal. Specifically, CT-DBS within the lateral wing of the central lateral nucleus and the surrounding medial dorsal thalamic tegmental tract (DTTm) produces a rapid and robust modulation of performance and arousal, as measured by neuronal activity in the frontal cortex and striatum. Notably, the most robust and reliable behavioral and physiological responses resulted when we implemented a novel method of CT-DBS that orients and shapes the electric field within the DTTm using spatially separated DBS leads. Collectively, our results demonstrate that selective activation within the DTTm of the CT robustly regulates endogenous arousal and enhances cognitive performance in the intact NHP; these findings provide insights into the mechanism of CT-DBS and further support the development of CT-DBS as a therapy for reestablishing arousal regulation to support cognition in SBI patients. PMID:27582298

A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

PubMed

Grahn, Peter J; Mallory, Grant W; Khurram, Obaid U; Berry, B Michael; Hachmann, Jan T; Bieber, Allan J; Bennet, Kevin E; Min, Hoon-Ki; Chang, Su-Youne; Lee, Kendall H; Lujan, J L

2014-01-01

Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.

Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections

PubMed Central

Knippenberg, Ben; Page-Sharp, Madhu; Clark, Ben; Dyer, John; Batty, Kevin T.; Davis, Timothy M. E.

2016-01-01

Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 μg/liter, 14 μg/liter, 25 μg/liter, and 153 μg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections. PMID:27270283

Stability of Phosphatidylethanol in Dry Blood Spot Cards.

PubMed

Bakhireva, Ludmila N; Shrestha, Shikhar; Gutierrez, Hilda L; Berry, Mike; Schmitt, Cheryl; Sarangarm, Dusadee

2016-05-01

The analysis of phosphatidylethanol, a promising direct ethanol metabolite, in dry blood spots (PEth-DBS) is advantageous due to ease of storage, transportation and minimal invasiveness of capillary blood collection. One potential application of PEth-DBS is to confirm prenatal alcohol exposure in newborns suspected of FASD; however, stability of PEth-DBS is largely unknown. Phlebotomized samples from 31 adults with a history of alcoholism, admitted to the University of New Mexico Emergency Department, were analyzed for blood alcohol content and pipetted onto DBS cards (13 spots per patient). The first spot was analyzed within 2 weeks of collection for a baseline PEth; the remaining 12 spots were allocated into three temperature conditions (room temperature, 4°C, -80°C) for the repeated measures analysis. In addition, 5 newborn DBS samples with a baseline PEth>LOD were obtained from a prospective cohort at UNM and re-analyzed at 4 months after storage at -80°C. A mixed linear model was fitted to examine the effects of temperature, time and temperature-time interaction on PEth degradation over the first 9 months. The baseline PEth levels were 592.8 ± 86.7 ng/ml and 18.3 ± 4.8 ng/ml in adult and newborn samples, respectively. All DBS samples remained positive in successive samples in all temperature conditions. Results of mixed linear model demonstrated a significant effect of temperature (P < 0.001) on PEth degradation over 9 months. PEth-DBS appears to be relatively stable, especially when stored at lower temperatures. These initial results are encouraging and highlight the PEth-DBS potential in retrospective assessment of alcohol exposure. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Stability of Phosphatidylethanol in Dry Blood Spot Cards

PubMed Central

Bakhireva, Ludmila N.; Shrestha, Shikhar; Gutierrez, Hilda L.; Berry, Mike; Schmitt, Cheryl; Sarangarm, Dusadee

2016-01-01

Background The analysis of phosphatidylethanol, a promising direct ethanol metabolite, in dry blood spots (PEth-DBS) is advantageous due to ease of storage, transportation and minimal invasiveness of capillary blood collection. One potential application of PEth-DBS is to confirm prenatal alcohol exposure in newborns suspected of FASD; however, stability of PEth-DBS is largely unknown. Methods Phlebotomized samples from 31 adults with a history of alcoholism, admitted to the University of New Mexico Emergency Department, were analyzed for blood alcohol content and pipetted onto DBS cards (13 spots per patient). The first spot was analyzed within 2 weeks of collection for a baseline PEth; the remaining 12 spots were allocated into three temperature conditions (room temperature, 4°C, −80°C) for the repeated measures analysis. In addition, 5 newborn DBS samples with a baseline PEth>LOD were obtained from a prospective cohort at UNM and re-analyzed at 4 months after storage at −80°C. A mixed linear model was fitted to examine the effects of temperature, time and temperature–time interaction on PEth degradation over the first 9 months. Results The baseline PEth levels were 592.8 ± 86.7 ng/ml and 18.3 ± 4.8 ng/ml in adult and newborn samples, respectively. All DBS samples remained positive in successive samples in all temperature conditions. Results of mixed linear model demonstrated a significant effect of temperature (P < 0.001) on PEth degradation over 9 months. Conclusions PEth-DBS appears to be relatively stable, especially when stored at lower temperatures. These initial results are encouraging and highlight the PEth-DBS potential in retrospective assessment of alcohol exposure. PMID:26519350

Short-chain fatty acid sensing in rat duodenum

PubMed Central

Akiba, Yasutada; Inoue, Takuya; Kaji, Izumi; Higashiyama, Masaaki; Narimatsu, Kazuyuki; Iwamoto, Ken-ichi; Watanabe, Masahiko; Guth, Paul H; Engel, Eli; Kuwahara, Atsukazu; Kaunitz, Jonathan D

2015-01-01

Intraduodenal fatty acids (FA) and bacterial overgrowth, which generate short-chain FAs (SCFAs), have been implicated in the generation of functional dyspepsia symptoms. We studied the mechanisms by which luminal SCFA perfusion affects duodenal HCO3− secretion (DBS), a measure of mucosal neurohumoral activation. Free fatty acid receptor (FFAR) 1 (FFA1), which binds long-chain FA (LCFA), and SCFA receptors FFA2 and FFA3 were immunolocalised to duodenal enteroendocrine cells. FFA3 colocalised with glucagon-like peptide (GLP)-1, whereas FFA2 colocalised with 5-HT. Luminal perfusion of the SCFA acetate or propionate increased DBS, enhanced by dipeptidyl peptidase-IV (DPPIV) inhibition, at the same time as increasing GLP-2 portal blood concentrations. Acetate-induced DBS was partially inhibited by monocarboxylate/HCO3− exchanger inhibition without affecting GLP-2 release, implicating acetate absorption in the partial mediation of DBS. A selective FFA2 agonist dose-dependently increased DBS, unaffected by DPPIV inhibition or by cholecystokinin or 5-HT3 receptor antagonists, but was inhibited by atropine and a 5-HT4 antagonist. By contrast, a selective FFA1 agonist increased DBS accompanied by GLP-2 release, enhanced by DPPIV inhibition and inhibited by a GLP-2 receptor antagonist. Activation of FFA1 by LCFA and presumably FFA3 by SCFA increased DBS via GLP-2 release, whereas FFA2 activation stimulated DBS via muscarinic and 5-HT4 receptor activation. SCFA/HCO3− exchange also appears to be present in the duodenum. The presence of duodenal fatty acid sensing receptors that signal hormone release and possibly signal neural activation may be implicated in the pathogenesis of functional dyspepsia. PMID:25433076

Bilateral subthalamic deep brain stimulation initial impact on nonmotor and motor symptoms in Parkinson's disease

PubMed Central

Kurcova, Sandra; Bardon, Jan; Vastik, Miroslav; Vecerkova, Marketa; Frolova, Monika; Hvizdosova, Lenka; Nevrly, Martin; Mensikova, Katerina; Otruba, Pavel; Krahulik, David; Kurca, Egon; Sivak, Stefan; Zapletalova, Jana; Kanovsky, Petr

2018-01-01

Abstract Numerous studies document significant improvement in motor symptoms in patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN-DBS). However, little is known about the initial effects of STN-DBS on nonmotor domains. Our objective was to elucidate the initial effects of STN-DBS on non-motor and motor symptoms in PD patients in a 4-month follow-up. This open prospective study followed 24 patients with PD who underwent STN-DBS. The patients were examined using dedicated rating scales preoperatively and at 1 and 4 months following STN-DBS to determine initial changes in motor and nonmotor symptoms. Patients at month 1 after STN-DBS had significantly reduced the Parkinson's disease Questionnaire scores (P = .018) and Scales for Outcomes in Parkinson's disease – Autonomic scores (P = .002); these scores had increased at Month 4 after DBS-STN. Nonmotor Symptoms Scale for Parkinson's Disease had improved significantly at Month 1 (P < .001); at Month 4, it remained significantly lower than before stimulation (P = .036). There was no significant difference in The Parkinson's Disease Sleep Scaleat Month 1 and significant improvement at Month 4 (P = .026). There were no significant changes in The Female Sexual Function Index or International Index of Erectile Function. Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III scores show significant improvements at Month 1 (P < .001) and at Month 4 (P < .001). STN-DBS in patients with advanced PD clearly improves not only motor symptoms, but also several domains of nonmotor functions, namely sleep, autonomic functions and quality of life quickly following the start of stimulation. PMID:29384860

Evaluation of a manual DNA extraction protocol and an isothermal amplification assay for detecting HIV-1 DNA from dried blood spots for use in resource-limited settings.

PubMed

Jordan, Jeanne A; Ibe, Christine O; Moore, Miranda S; Host, Christel; Simon, Gary L

2012-05-01

In resource-limited settings (RLS) dried blood spots (DBS) are collected on infants and transported through provincial laboratories to a central facility where HIV-1 DNA PCR testing is performed using specialized equipment. Implementing a simpler approach not requiring such equipment or skilled personnel could allow the more numerous provincial laboratories to offer testing, improving turn-around-time to identify and treat infected infants sooner. Assess performances of a manual DNA extraction method and helicase-dependent amplification (HDA) assay for detecting HIV-1 DNA from DBS. 60 HIV-1 infected adults were enrolled, blood samples taken and DBS made. DBS extracts were assessed for DNA concentration and beta globin amplification using PCR and melt-curve analysis. These same extracts were then tested for HIV-1 DNA using HDA and compared to results generated by PCR and pyrosequencing. Finally, HDA limit of detection (LOD) studies were performed using DBS extracts prepared with known numbers of 8E5 cells. The manual extraction protocol consistently yielded high concentrations of amplifiable DNA from DBS. LOD assessment demonstrated HDA detected ∼470 copies/ml of HIV-1 DNA extracts in 4/4 replicates. No statistical difference was found using the McNemar's test when comparing HDA to PCR for detecting HIV-1 DNA from DBS. Using just a magnet, heat block and pipettes, the manual extraction protocol and HDA assay detected HIV-1 DNA from DBS at levels that would be useful for early infant diagnosis. Next steps will include assessing HDA for non-B HIV-1 subtypes recognition and comparison to Roche HIV-1 DNA v1.5 PCR assay. Copyright © 2012 Elsevier B.V. All rights reserved.

Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

PubMed Central

Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

2015-01-01

Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

Use of a commercial ELISA for the detection of measles-specific immunoglobulin G (IgG) in dried blood spots collected from children living in low-resource settings.

PubMed

Colson, K Ellicott; Potter, Alan; Conde-Glez, Carlos; Hernandez, Bernardo; Ríos-Zertuche, Diego; Zúñiga-Brenes, Paola; Iriarte, Emma; Mokdad, Ali H

2015-09-01

Seroepidemiological monitoring of population immunity to vaccine-preventable diseases is critical to prevent future outbreaks. Dried blood spots (DBS), drops of capillary blood dried on filter paper, are an affordable, minimally invasive alternative to venipuncture for collecting blood in field settings. However, few proven methods exist to analyze DBS for the presence of protective antibodies. This study validates a novel technique for measuring measles-specific immunoglobulin G (IgG) in capillary DBS using a commercial ELISA. The predictive performance of a new method for analyzing DBS was tested by comparing matched serum and DBS samples from 50 children. The accuracy, precision, and reliability of the procedure were evaluated, and the optimal cut points to classify positive and negative samples were determined. The method was then applied to 1,588 DBS collected during a large survey of children in Mexico and Nicaragua. Measles-specific IgG in serum samples were 62% negative, 10% equivocal, and 28% positive. In comparisons with matched serum, DBS results were 100% sensitive and 96 · 8% specific, and agreed in 46 of 50 (92%) cases. The inter-assay and intra-assay coefficients of variation from kit-provided controls were greater than desired (24.8% and 8.4%, respectively). However, in predictive simulations the average misclassification was only 3.9%. Procedures were found to be acceptable to surveyors and participants. Analyzing DBS collected in low-resources settings is a feasible and accurate means of measuring population immunity to measles and should be used to generate objective measures of health status and health system performance. © 2015 Wiley Periodicals, Inc.

Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome.

PubMed

Eddelman, Daniel; Wewel, Joshua; Wiet, R Mark; Metman, Leo V; Sani, Sepehr

2017-01-01

Patients with previously implanted cranial devices pose a special challenge in deep brain stimulation (DBS) surgery. We report the implantation of bilateral DBS leads in a patient with a cochlear implant. Technical nuances and long-term interdevice functionality are presented. A 70-year-old patient with advancing Parkinson's disease and a previously placed cochlear implant for sensorineural hearing loss was referred for placement of bilateral DBS in the subthalamic nucleus (STN). Prior to DBS, the patient underwent surgical removal of the subgaleal cochlear magnet, followed by stereotactic MRI, frame placement, stereotactic computed tomography (CT), and merging of imaging studies. This technique allowed for successful computational merging, MRI-guided targeting, and lead implantation with acceptable accuracy. Formal testing and programming of both the devices were successful without electrical interference. Successful DBS implantation with high resolution MRI-guided targeting is technically feasible in patients with previously implanted cochlear implants by following proper precautions.

Engineering the next generation of clinical deep brain stimulation technology.

PubMed

McIntyre, Cameron C; Chaturvedi, Ashutosh; Shamir, Reuben R; Lempka, Scott F

2015-01-01

Deep brain stimulation (DBS) has evolved into a powerful clinical therapy for a range of neurological disorders, but even with impressive clinical growth, DBS technology has been relatively stagnant over its history. However, enhanced collaborations between neural engineers, neuroscientists, physicists, neurologists, and neurosurgeons are beginning to address some of the limitations of current DBS technology. These interactions have helped to develop novel ideas for the next generation of clinical DBS systems. This review attempts collate some of that progress with two goals in mind. First, provide a general description of current clinical DBS practices, geared toward educating biomedical engineers and computer scientists on a field that needs their expertise and attention. Second, describe some of the technological developments that are currently underway in surgical targeting, stimulation parameter selection, stimulation protocols, and stimulation hardware that are being directly evaluated for near term clinical application. Copyright © 2015 Elsevier Inc. All rights reserved.

Deep brain stimulation for psychiatric disorders: Is there an impact on social functioning?

PubMed Central

Saleh, Christian; Hasler, Gregor

2017-01-01

Background: Deep brain stimulation (DBS) for refractory psychiatric disorders shows promising effects on symptom-reduction, however, little is known regarding the effects of DBS on social outcome. Methods: A PubMed search based on original studies of DBS for psychiatric disorders [treatment resistant depression (TRD), Gilles de la Tourette's syndrome (GTS), and obsessive compulsive disorder (OCD)] was conducted. Data on social outcome following surgery were extracted and analyzed. Results: Social functioning was not a primary outcome measure in the reviewed article. The literature is incomplete and inconclusive on this variable, however from the reported data, there is some evidence that DBS has the potential to improve social functioning. Conclusions: More systematic and detailed data gathering and reporting on social outcome with longer follow-ups are needed to evaluate more exhaustively the role of DBS in refractory psychiatric disorders. PMID:28781911

Monitoring the onset of neuromuscular blockade with double burst stimulation (DBS).

PubMed

Gorgias, N; Maidatsi, P; Zaralidou, A; Ourailoglou, V; Fakidou, A; Giala, M

1998-11-01

The present study was undertaken to evaluate the suitability of the DBS mode in the determination of the proper time to perform tracheal intubation following cisatracurium muscle relaxation. The DBS3.3 pattern was administered to the ulnar nerve at the wrist in 45 patients paralyzed with cisatracurium 0.15 mg.kg-1 and tracheal intubation was attempted immediately after the disappearance of both palpable contractions of the adductor pollicis. Intubation conditions were assessed with a standard four-graded scoring system and the onset time of the relaxant was determined. Forty-two patients (93%) exhibited acceptable intubation conditions as soon as both responses to DBS were absent and the estimated apparent onset time, according to the stimulation mode applied, was 114.68 +/- 13.2 sec. Our data suggest that disappearance of both palpable responses to DBS3.3 may be used as an accurate predictor of acceptable intubation conditions, following nondepolarizing relaxants such as cisatracurium.

Bio-heat transfer model of deep brain stimulation-induced temperature changes

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

2006-12-01

There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

Evolution of Deep Brain Stimulation: Human Electrometer and Smart Devices Supporting the Next Generation of Therapy

PubMed Central

Lee, Kendall H.; Blaha, Charles D.; Garris, Paul A.; Mohseni, Pedram; Horne, April E.; Bennet, Kevin E.; Agnesi, Filippo; Bledsoe, Jonathan M.; Lester, Deranda B.; Kimble, Chris; Min, Hoon-Ki; Kim, Young-Bo; Cho, Zang-Hee

2010-01-01

Deep Brain Stimulation (DBS) provides therapeutic benefit for several neuropathologies including Parkinson’s disease (PD), epilepsy, chronic pain, and depression. Despite well established clinical efficacy, the mechanism(s) of DBS remains poorly understood. In this review we begin by summarizing the current understanding of the DBS mechanism. Using this knowledge as a framework, we then explore a specific hypothesis regarding DBS of the subthalamic nucleus (STN) for the treatment of PD. This hypothesis states that therapeutic benefit is provided, at least in part, by activation of surviving nigrostriatal dopaminergic neurons, subsequent striatal dopamine release, and resumption of striatal target cell control by dopamine. While highly controversial, we present preliminary data that are consistent with specific predications testing this hypothesis. We additionally propose that developing new technologies, e.g., human electrometer and closed-loop smart devices, for monitoring dopaminergic neurotransmission during STN DBS will further advance this treatment approach. PMID:20657744

Microsample analyses via DBS: challenges and opportunities.

PubMed

Henion, Jack; Oliveira, Regina V; Chace, Donald H

2013-10-01

The use of DBS is an appealing approach to employing microsampling techniques for the bioanalysis of samples, as has been demonstrated for the past 50 years in the metabolic screening of metabolites and diseases. In addition to its minimally invasive sample collection procedures and its economical merits, DBS microsampling benefits from the very high sensitivity, selectivity and multianalyte capabilities of LC-MS, which has been especially well demonstrated in newborn screening applications. Only a few microliters of a biological fluid are required for analysis, which also translates to significantly reduced demands on clinical samples from patients or from animals. Recently, the pharmaceutical industry and other arenas have begun to explore the utility and practicality of DBS microsampling. This review discusses the basis for why DBS techniques are likely to be part of the future, as well as offering insights into where these benefits may be realized.

Differential effects of deep brain stimulation on verbal fluency.

PubMed

Ehlen, Felicitas; Schoenecker, Thomas; Kühn, Andrea A; Klostermann, Fabian

2014-07-01

We aimed at gaining insights into principles of subcortical lexical processing. Therefore, effects of deep brain stimulation (DBS) in different target structures on verbal fluency (VF) were tested. VF was assessed with active vs. inactivated DBS in 13 and 14 patients with DBS in the vicinity of the thalamic ventral intermediate nucleus (VIM) and, respectively, of the subthalamic nucleus (STN). Results were correlated to electrode localizations in postoperative MRI, and compared to those of 12 age-matched healthy controls. Patients' VF performance was generally below normal. However, while activation of DBS in the vicinity of VIM provoked marked VF decline, it induced subtle phonemic VF enhancement in the vicinity of STN. The effects correlated with electrode localizations in left hemispheric stimulation sites. The results show distinct dependencies of VF on DBS in the vicinity of VIM vs. STN. Particular risks for deterioration occur in patients with relatively ventromedial thalamic electrodes. Copyright © 2014 Elsevier Inc. All rights reserved.

Successful deep brain stimulation of the nucleus accumbens in severe alcohol dependence is associated with changed performance monitoring.

PubMed

Kuhn, Jens; Gründler, Theo O J; Bauer, Robert; Huff, Wolfgang; Fischer, Adrian G; Lenartz, Doris; Maarouf, Mohammad; Bührle, Christian; Klosterkötter, Joachim; Ullsperger, Markus; Sturm, Volker

2011-10-01

Following recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psychometric scores and electrophysiological measures of cognitive control. In our patient, DBS achieved normalization of addictive behavior and craving. An electrophysiological marker of error processing (the error-related negativity) linked to anterior mid-cingulate cortex (aMCC) functioning was altered through DBS, an effect that could be reversed by periods without stimulation. Thus, this case supports the hypothesis that DBS of the NAc could have a positive effect on addiction trough a normalization of craving associated with aMCC dysfunction. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

Star on the horizon: The emergence of the direct broadcast satellite in American mass communications

NASA Astrophysics Data System (ADS)

Thomas, J. H.

1984-12-01

The purpose of this thesis is to describe the concept of broadcasting from satellites directly to the viewer equipped with a small, inexpensive receiving antenna, and the evolution of this technology as a means of commercial broadcast. Emphasis is placed on the problems of developing a regulatory framework for DBS by the Federal Communications Commission. The opposition of the existing broadcasters to the unregulated development of direct broadcast satellite (DBS) is explored in light of the possible effect that DBS may have on the economic base, audience, and advertising revenue of existing broadcasters. The information for this study was obtained from government documents, legal journals, books and the popular press. Two basic conclusions are drawn from this study: First, that the existing broadcasters have opposed the marketplace development of DBS, and second, that DBS does not pose as great a threat, at least in the near term, as the broadcasters fear.

Medicare's "Global" terrorism: where is the pay for performance?

PubMed

Reed, R Lawrence; Luchette, Fred A; Esposito, Thomas J; Pyrz, Karen; Gamelli, Richard L

2008-02-01

Medicare and Medicaid Services (CMS) payment policies for surgical operations are based on a global package concept. CMS' physician fee schedule splits the global package into preoperative, intraoperative, and postoperative components of each procedure. We hypothesized that these global package component valuations were often lower than comparable evaluation and management (E&M) services and that billing for E&M services instead of the operation could often be more profitable. Our billing database and Trauma Registry were queried for the operative procedures and hospital lengths of stay for trauma patients during the past 5 years. Determinations of preoperative, intraoperative, and postoperative payments were calculated for 10-day and 90-day global packages, comparing them to CMS payments for comparable E&M codes. Of 90-day and 10-day Current Procedural Terminology codes, 88% and 100%, respectively, do not pay for the comprehensive history and physical that trauma patients usually receive, whereas 41% and 98%, respectively, do not even meet payment levels for a simple history and physical. Of 90-day global package procedures, 70% would have generated more revenue had comprehensive daily visits been billed instead of the operation ($3,057,500 vs. $1,658,058). For 10-day global package procedures, 56% would have generated more revenue with merely problem-focused daily visits instead of the operation ($161,855 vs. $156,318). Medicare's global surgical package underpays E&M services in trauma patients. In most cases, trauma surgeons would fare better by not billing for operations to receive higher reimbursement for E&M services that are considered "bundled" in the global package payment.

Discussion boards: boring no more!

PubMed

Adelman, Deborah S; Nogueras, Debra J

2013-01-01

Creating discussion boards (DBs) that capture student imaginations and contain meaningful interactions can be a difficult process. Traditional DBs use a question-and-answer format that often is boring for both the student and instructor. The authors present creative approaches to DBs that result in lively debates and student-to-student and student-to-faculty interactions, including role playing, blogging, wikis, and the use of voice.

Faculty Perceptions of Loughborough's Online Reading List System (LORLS) at Dublin Business School (DBS)

ERIC Educational Resources Information Center

O'Neill, Marie; Musto, Lara

2017-01-01

Using a mixed methods research approach this study explores faculty perceptions of LORLS at DBS. Data generated by the study will inform advocacy, marketing and training initiatives to promote the platform. The study concludes with a number of deductive and inductive findings. The first is that although DBS faculty are highly predisposed to using…

Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations.

PubMed

Ramirez-Zamora, Adolfo; Smith, Heather; Kumar, Vignessh; Prusik, Julia; Phookan, Sujoy; Pilitsis, Julie G

2016-01-01

Although thalamic deep brain stimulation (DBS) has been established as an effective therapy for refractory tremor in Parkinson's disease and essential tremor, reports investigating the efficacy of posterior subthalamic area (PSA) DBS for severe, debilitating tremors continue to emerge. However, questions regarding the optimal anatomical target, surgical approach, programming paradigms and effectiveness compared to other targets remain. In this report, we aimed to review the current literature to assess different stereotactic techniques, anatomical considerations, adverse effects and stimulation settings in PSA DBS. A comprehensive literature review was performed searching for articles discussing tremors and PSA stimulation. We performed a quantitative analysis comparing different DBS tremor targets. Tremor improvement is consistently documented in most reports with an average reduction in tremor of 79% depending on the specific tremor syndrome. Tremor benefit in patients with multiple sclerosis (MS) tremor was significantly higher than for other stimulation targets. Transient paresthesias, imbalance, dizziness and dysarthria are the most common side effects with PSA DBS. PSA DBS is an effective and safe treatment for tremor control and should be considered in patients with refractory tremors with associated cerebellar or dystonic features, proximal tremors and MS tremor. © 2016 S. Karger AG, Basel.

Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank

PubMed Central

Ramirez-Zamora, Adolfo; Giordano, James J.; Gunduz, Aysegul; Brown, Peter; Sanchez, Justin C.; Foote, Kelly D.; Almeida, Leonardo; Starr, Philip A.; Bronte-Stewart, Helen M.; Hu, Wei; McIntyre, Cameron; Goodman, Wayne; Kumsa, Doe; Grill, Warren M.; Walker, Harrison C.; Johnson, Matthew D.; Vitek, Jerrold L.; Greene, David; Rizzuto, Daniel S.; Song, Dong; Berger, Theodore W.; Hampson, Robert E.; Deadwyler, Sam A.; Hochberg, Leigh R.; Schiff, Nicholas D.; Stypulkowski, Paul; Worrell, Greg; Tiruvadi, Vineet; Mayberg, Helen S.; Jimenez-Shahed, Joohi; Nanda, Pranav; Sheth, Sameer A.; Gross, Robert E.; Lempka, Scott F.; Li, Luming; Deeb, Wissam; Okun, Michael S.

2018-01-01

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice. PMID:29416498

Quantification of sulfatides in dried blood and urine spots from metachromatic leukodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry.

PubMed

Barcenas, Mariana; Suhr, Teryn R; Scott, C Ronald; Turecek, Frantisek; Gelb, Michael H

2014-06-10

Treatments are being developed for metachromatic leukodystrophy (MLD), suggesting the need for eventual newborn screening. Previous studies have shown that sulfatide molecular species are increased in the urine of MLD patients compared to samples from non-MLD individuals, but there is no data using dried blood spots (DBS), the most common sample available for newborn screening laboratories. We used ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) to quantify sulfatides in DBS and dried urine spots from 14 MLD patients and 50 non-MLD individuals. Several sulfatide molecular species were increased in dried urine samples from all MLD samples compared to non-MLD samples. Sulfatides, especially low molecular species, were increased in DBS from MLD patients, but the sulfatide levels were relatively low. There was good separation in sulfatide levels between MLD and non-MLD samples when dried urine spots were used, but not with DBS, because DBS from non-MLD individuals have measurable levels of sulfatides. Sulfatide accumulation studies in urine, but not in DBS, emerges as the method of choice if newborn screening is to be proposed for MLD. Copyright © 2013 Elsevier B.V. All rights reserved.

Subthalamic nucleus deep brain stimulation improves deglutition in Parkinson's disease.

PubMed

Ciucci, Michelle R; Barkmeier-Kraemer, Julie M; Sherman, Scott J

2008-04-15

Relatively little is known about the role of the basal ganglia in human deglutition. Deep brain stimulation (DBS) 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 subthalamic nuclei (STN) DBS on the oral and pharyngeal stages of deglutition in individuals with Parkinson's Disease (PD). It was hypothesized that DBS would be associated with improved deglutition. Within participant, comparisons were made between DBS in the ON and OFF conditions using the dependent variables: pharyngeal transit time, maximal hyoid bone excursion, oral total composite score, and pharyngeal total composite score. Significant improvement occurred for the pharyngeal composite score and pharyngeal transit time in the DBS ON condition compared with DBS OFF. Stimulation of the STN may excite thalamocortical or brainstem targets to sufficiently overcome the bradykinesia/hypokinesia associated with PD and return some pharyngeal stage motor patterns to performance levels approximating those of "normal" deglutition. However, the degree of hyoid bone excursion and oral stage measures did not improve, suggesting that these motor acts may be under the control of different sensorimotor pathways within the basal ganglia. 2007 Movement Disorder Society

Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear

PubMed Central

Rodriguez-Romaguera, Jose; Do Monte, Fabricio H. M.; Quirk, Gregory J.

2012-01-01

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD. PMID:22586125

Mechanisms Underlying Decision-Making as Revealed by Deep-Brain Stimulation in Patients with Parkinson's Disease.

PubMed

Herz, Damian M; Little, Simon; Pedrosa, David J; Tinkhauser, Gerd; Cheeran, Binith; Foltynie, Tom; Bogacz, Rafal; Brown, Peter

2018-04-23

To optimally balance opposing demands of speed and accuracy during decision-making, we must flexibly adapt how much evidence we require before making a choice. Such adjustments in decision thresholds have been linked to the subthalamic nucleus (STN), and therapeutic STN deep-brain stimulation (DBS) has been shown to interfere with this function. Here, we performed continuous as well as closed-loop DBS of the STN while Parkinson's disease patients performed a perceptual decision-making task. Closed-loop STN DBS allowed temporally patterned STN stimulation and simultaneous recordings of STN activity. This revealed that DBS only affected patients' ability to adjust decision thresholds if applied in a specific temporally confined time window during deliberation. Only stimulation in that window diminished the normal slowing of response times that occurred on difficult trials when DBS was turned off. Furthermore, DBS eliminated a relative, time-specific increase in STN beta oscillations and compromised its functional relationship with trial-by-trial adjustments in decision thresholds. Together, these results provide causal evidence that the STN is involved in adjusting decision thresholds in distinct, time-limited processing windows during deliberation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank.

PubMed

Ramirez-Zamora, Adolfo; Giordano, James J; Gunduz, Aysegul; Brown, Peter; Sanchez, Justin C; Foote, Kelly D; Almeida, Leonardo; Starr, Philip A; Bronte-Stewart, Helen M; Hu, Wei; McIntyre, Cameron; Goodman, Wayne; Kumsa, Doe; Grill, Warren M; Walker, Harrison C; Johnson, Matthew D; Vitek, Jerrold L; Greene, David; Rizzuto, Daniel S; Song, Dong; Berger, Theodore W; Hampson, Robert E; Deadwyler, Sam A; Hochberg, Leigh R; Schiff, Nicholas D; Stypulkowski, Paul; Worrell, Greg; Tiruvadi, Vineet; Mayberg, Helen S; Jimenez-Shahed, Joohi; Nanda, Pranav; Sheth, Sameer A; Gross, Robert E; Lempka, Scott F; Li, Luming; Deeb, Wissam; Okun, Michael S

2017-01-01

The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.

Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.

PubMed

Picillo, Marina; Vincos, Gustavo B; Sammartino, Francesco; Lozano, Andres M; Fasano, Alfonso

2017-05-01

Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS). Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics. After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS. Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropsychological changes following deep brain stimulation surgery for Parkinson's disease: comparisons of treatment at pallidal and subthalamic targets versus best medical therapy.

PubMed

Rothlind, Johannes C; York, Michele K; Carlson, Kim; Luo, Ping; Marks, William J; Weaver, Frances M; Stern, Matthew; Follett, Kenneth; Reda, Domenic

2015-06-01

Deep brain stimulation (DBS) improves motor symptoms in Parkinson's disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. Neuropsychological functioning was assessed in patients with Parkinson's disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. NCT00056563 and NCT01076452. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses.

PubMed

Lange, Berit; Cohn, Jennifer; Roberts, Teri; Camp, Johannes; Chauffour, Jeanne; Gummadi, Nina; Ishizaki, Azumi; Nagarathnam, Anupriya; Tuaillon, Edouard; van de Perre, Philippe; Pichler, Christine; Easterbrook, Philippa; Denkinger, Claudia M

2017-11-01

Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV. We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias. For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%-99%) and 100% (95%CI:99-100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95-99) and 99% (CI95%:98-100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews. HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

Deep Brain Stimulation in Early Parkinson’s Disease: Enrollment Experience from a Pilot Trial

PubMed Central

Charles, PD; Dolhun, RM; Gill, CE; Davis, TL; Bliton, MJ; Tramontana, MG; Salomon, RM; Wang; Hedera, P; Phibbs, FT; Neimat, JS; Konrad, PE

2011-01-01

Background Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson’s disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression. Methods We are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events. Results 30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion. Conclusion This report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD. PMID:22104012

Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease.

PubMed

Fumagalli, Manuela; Marceglia, Sara; Cogiamanian, Filippo; Ardolino, Gianluca; Picascia, Marta; Barbieri, Sergio; Pravettoni, Gabriella; Pacchetti, Claudio; Priori, Alberto

2015-07-01

The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies.

PubMed

Wickremsinhe, Enaksha R; Perkins, Everett J

2015-03-01

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 μL blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animal-often to a single collection per mouse-thus necessitating dosing multiple mice to generate a pharmacokinetic profile in a sparse-sampling design. Compared with traditional methods, dried blood spot (DBS) analysis requires smaller volumes of blood (15 to 20 μL), thus supporting serial blood sampling and the generation of a complete pharmacokinetic profile from a single mouse. Here we compare plasma-derived data with DBS-derived data, explain how to adopt DBS sampling to support discovery mouse studies, and describe how to generate pharmacokinetic and pharmacodynamic data from a single mouse. Executing novel study designs that use DBS enhances the ability to identify and streamline better drug candidates during drug discovery. Implementing DBS sampling can reduce the number of mice needed in a drug discovery program. In addition, the simplicity of DBS sampling and the smaller numbers of mice needed translate to decreased study costs. Overall, DBS sampling is consistent with 3Rs principles by achieving reductions in the number of animals used, decreased restraint-associated stress, improved data quality, direct comparison of interanimal variability, and the generation of multiple endpoints from a single study.

Detection of Streptococcus pneumoniae and Haemophilus influenzae Type B by Real-Time PCR from Dried Blood Spot Samples among Children with Pneumonia: A Useful Approach for Developing Countries

PubMed Central

Selva, Laura; Benmessaoud, Rachid; Lanaspa, Miguel; Jroundi, Imane; Moraleda, Cinta; Acacio, Sozinho; Iñigo, Melania; Bastiani, Alien; Monsonis, Manuel; Pallares, Roman; Bassat, Quique; Muñoz-Almagro, Carmen

2013-01-01

Background Dried blood spot (DBS) is a reliable blood collection method for storing samples at room temperature and easily transporting them. We have previously validated a Real-Time PCR for detection of Streptococcus pneumoniae in DBS. The objective of this study was to apply this methodology for the diagnosis of S. pneumoniae and Haemophilus influenzae b (Hib) in DBS samples of children with pneumonia admitted to two hospitals in Mozambique and Morocco. Methods Ply and wzg genes of S. pneumoniae and bexA gene of Hib, were used as targets of Real-Time PCR. 329 DBS samples of children hospitalized with clinical diagnosis of pneumonia were tested. Results Real-Time PCR in DBS allowed for a significant increase in microbiological diagnosis of S. pneumoniae and Hib. When performing blood bacterial culture, only ten isolates of S. pneumoniae and none of Hib were detected (3·0% positivity rate, IC95% 1·4-5·5%). Real-Time PCR from DBS samples increased the detection yield by 4x fold, as 30 S. pneumoniae and 11 Hib cases were detected (12·4% positivity rate, IC95% 9·0-16·5%; P<0·001). Conclusion Real-Time PCR applied in DBS may be a valuable tool for improving diagnosis and surveillance of pneumonia caused by S. pneumoniae or Hib in developing countries. PMID:24116190

Deep brain stimulation for movement disorders. Considerations on 276 consecutive patients.

PubMed

Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Carella, Francesco; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekay, Edvin; Broggi, Giovanni

2011-10-01

The links between Stn DBS and advanced Parkinson disease, and between GPi DBS and dystonia are nearly universally accepted by the neurologists and neurosurgeons. Nevertheless, in some conditions, targets such as the ventral thalamus and the Zona Incerta may be considered to optimize the results and avoid the side effects. Positive and negative aspects of current DBS treatments justify the research of new targets, new stimulation programs and new hardware. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. 276 patients were affected by movement disorders. The DBS targets included Stn, GPi, Voa, Vop, Vim, CM-pf, cZi, IC. The long-term follow-up is reported and related to the chosen target. DBS gave a new therapeutic option to patients affected by severe movement disorders, and in some cases resolved life-threatening pathological conditions that would otherwise result in the death of the patient, such as in status dystonicus, and post-stroke hemiballismus. Nevertheless, the potential occurrence of severe complications still limit a wider use of DBS. At today, the use of DBS in severe movement disorders is strongly positive even if further investigations and studies are needed to unveil potential new applications, and to refine the selection criteria for the actual indications and targets. The experience of different targets may be useful to guide and tailor the target choice to the individual clinical condition.

The effect of deep brain stimulation on the non-motor symptoms of Parkinson’s disease: a critical review of the current evidence

PubMed Central

Kurtis, Mónica M; Rajah, Thadshani; Delgado, Luisa F; Dafsari, Haidar S

2017-01-01

The benefit of deep brain stimulation (DBS) in controlling the motor symptoms of Parkinson’s disease is well established, however, the impact on the non-motor symptoms (NMS) remains to be elucidated, although the growing investigative efforts are promising. This article reviews the reported data and considers the level of evidence available with regard to the effect of DBS on NMS total burden and on the cognitive, neuropsychiatric, sleep, pain, dysautonomic, and weight domains. Multiple case series suggest that DBS improves the burden of NMS by reducing prevalence, intensity, and non-motor fluctuations. There is level I evidence on the effect of DBS on cognition and mood. Slight cognitive decline has been reported in most class I studies, although the functional effect is probably minimal. Two randomized prospective studies reported no change in depression while improvement of anxiety has been reported by a class I trial. Prospective cohort studies point to improvement of hyperdopaminergic behaviors, such as impulse control disorders, while others report that hypodopaminergic states, like apathy, can appear after DBS. There is only class III evidence supporting the benefit of DBS on other NMS such as nocturnal sleep, pain, dysautonomia (urinary, gastrointestinal, cardiovascular, and sweating), and weight loss. Although preliminary results are promising, randomized prospectively controlled trials with NMS as primary end points are necessary to further explore the effect of DBS on these often invalidating symptoms and offer conclusions about efficacy. PMID:28725706

The effect of deep brain stimulation on the non-motor symptoms of Parkinson's disease: a critical review of the current evidence.

PubMed

Kurtis, Mónica M; Rajah, Thadshani; Delgado, Luisa F; Dafsari, Haidar S

2017-01-01

The benefit of deep brain stimulation (DBS) in controlling the motor symptoms of Parkinson's disease is well established, however, the impact on the non-motor symptoms (NMS) remains to be elucidated, although the growing investigative efforts are promising. This article reviews the reported data and considers the level of evidence available with regard to the effect of DBS on NMS total burden and on the cognitive, neuropsychiatric, sleep, pain, dysautonomic, and weight domains. Multiple case series suggest that DBS improves the burden of NMS by reducing prevalence, intensity, and non-motor fluctuations. There is level I evidence on the effect of DBS on cognition and mood. Slight cognitive decline has been reported in most class I studies, although the functional effect is probably minimal. Two randomized prospective studies reported no change in depression while improvement of anxiety has been reported by a class I trial. Prospective cohort studies point to improvement of hyperdopaminergic behaviors, such as impulse control disorders, while others report that hypodopaminergic states, like apathy, can appear after DBS. There is only class III evidence supporting the benefit of DBS on other NMS such as nocturnal sleep, pain, dysautonomia (urinary, gastrointestinal, cardiovascular, and sweating), and weight loss. Although preliminary results are promising, randomized prospectively controlled trials with NMS as primary end points are necessary to further explore the effect of DBS on these often invalidating symptoms and offer conclusions about efficacy.

Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease.

PubMed

Cury, Rubens G; Galhardoni, Ricardo; Teixeira, Manoel J; Dos Santos Ghilardi, Maria G; Silva, Valquiria; Myczkowski, Martin L; Marcolin, Marco A; Barbosa, Egberto R; Fonoff, Erich T; Ciampi de Andrade, Daniel

2016-12-01

Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

Mechanisms and targets of deep brain stimulation in movement disorders.

PubMed

Johnson, Matthew D; Miocinovic, Svjetlana; McIntyre, Cameron C; Vitek, Jerrold L

2008-04-01

Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

Using Dried Blood Spot Sampling to Improve Data Quality and Reduce Animal Use in Mouse Pharmacokinetic Studies

PubMed Central

Wickremsinhe, Enaksha R; Perkins, Everett J

2015-01-01

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 µL blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animal—often to a single collection per mouse—thus necessitating dosing multiple mice to generate a pharmacokinetic profile in a sparse-sampling design. Compared with traditional methods, dried blood spot (DBS) analysis requires smaller volumes of blood (15 to 20 µL), thus supporting serial blood sampling and the generation of a complete pharmacokinetic profile from a single mouse. Here we compare plasma-derived data with DBS-derived data, explain how to adopt DBS sampling to support discovery mouse studies, and describe how to generate pharmacokinetic and pharmacodynamic data from a single mouse. Executing novel study designs that use DBS enhances the ability to identify and streamline better drug candidates during drug discovery. Implementing DBS sampling can reduce the number of mice needed in a drug discovery program. In addition, the simplicity of DBS sampling and the smaller numbers of mice needed translate to decreased study costs. Overall, DBS sampling is consistent with 3Rs principles by achieving reductions in the number of animals used, decreased restraint-associated stress, improved data quality, direct comparison of interanimal variability, and the generation of multiple endpoints from a single study. PMID:25836959

Thalamic deep brain stimulation decelerates automatic lexical activation.

PubMed

Ehlen, Felicitas; Vonberg, Isabelle; Tiedt, Hannes O; Horn, Andreas; Fromm, Ortwin; Kühn, Andrea A; Klostermann, Fabian

2017-02-01

Deep Brain Stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) is a therapeutic option for patients with essential tremor. Despite a generally low risk of side effects, declines in verbal fluency (VF) have previously been reported. We aimed to specify effects of VIM-DBS on major cognitive operations needed for VF task performance, represented by clusters and switches. Clusters are word production spurts, thought to arise from automatic activation of associated information pertaining to a given lexical field. Switches are slow word-to-word transitions, presumed to indicate controlled operations for stepping from one lexical field to another. Thirteen essential tremor patients with VIM-DBS performed verbal fluency tasks in their VIM-DBS ON and OFF conditions. Clusters and switches were formally defined by mathematical criteria. All results were compared to those of fifteen healthy control subjects, and significant OFF-ON-change scores were correlated to stimulation parameters. Patients produced fewer words than healthy controls. DBS ON compared to DBS OFF aggravated this deficit by prolonging the intervals between words within clusters, whereas switches remained unaffected. This stimulation effect correlated with more anterior electrode positions. VIM-DBS seems to influence word output dynamics during verbal fluency tasks on the level of word clustering. This suggests a perturbation of automatic lexical co-activation by thalamic stimulation, particularly if delivered relatively anteriorly. The findings are discussed in the context of the hypothesized role of the thalamus in lexical processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Programming Deep Brain Stimulation for Parkinson's Disease: The Toronto Western Hospital Algorithms.

PubMed

Picillo, Marina; Lozano, Andres M; Kou, Nancy; Puppi Munhoz, Renato; Fasano, Alfonso

2016-01-01

Deep brain stimulation (DBS) is an established and effective treatment for Parkinson's disease (PD). After surgery, a number of extensive programming sessions are performed to define the most optimal stimulation parameters. Programming sessions mainly rely only on neurologist's experience. As a result, patients often undergo inconsistent and inefficient stimulation changes, as well as unnecessary visits. We reviewed the literature on initial and follow-up DBS programming procedures and integrated our current practice at Toronto Western Hospital (TWH) to develop standardized DBS programming protocols. We propose four algorithms including the initial programming and specific algorithms tailored to symptoms experienced by patients following DBS: speech disturbances, stimulation-induced dyskinesia and gait impairment. We conducted a literature search of PubMed from inception to July 2014 with the keywords "deep brain stimulation", "festination", "freezing", "initial programming", "Parkinson's disease", "postural instability", "speech disturbances", and "stimulation induced dyskinesia". Seventy papers were considered for this review. Based on the literature review and our experience at TWH, we refined four algorithms for: (1) the initial programming stage, and management of symptoms following DBS, particularly addressing (2) speech disturbances, (3) stimulation-induced dyskinesia, and (4) gait impairment. We propose four algorithms tailored to an individualized approach to managing symptoms associated with DBS and disease progression in patients with PD. We encourage established as well as new DBS centers to test the clinical usefulness of these algorithms in supplementing the current standards of care. Copyright © 2016 Elsevier Inc. All rights reserved.

Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients.

PubMed

Voges, Berthold R; Schmitt, Friedhelm C; Hamel, Wolfgang; House, Patrick M; Kluge, Christian; Moll, Christian K E; Stodieck, Stefan R

2015-08-01

In view of the regulatory function of the thalamus in the sleep-wake cycle, the impact of deep brain stimulation (DBS) of the anterior nucleus thalami (ANT) on sleep was assessed in a small consecutive cohort of epilepsy patients with standardized polysomnography (PSG). In nine patients treated with ANT-DBS (voltage 5 V, frequency 145 Hz, cyclic mode), the number of arousals during stimulation and nonstimulation periods, neuropsychiatric symptoms (npS), and seizure frequency were determined. Electroclinical arousals were triggered in 14.0 to 67.0% (mean 42.4 ± SD 16.8%) of all deep brain stimuli. Six patients reported npS. Nocturnal DBS voltages were reduced in eight patients (one patient without npS refused) and PSGs were repeated. Electroclinical arousals occurred between 1.4 and 6.7 (mean 3.3 ± 1.7) times more frequently during stimulation periods compared to nonstimulation periods; the number of arousals positively correlated with the level of DBS voltage (range 1 V to 5 V) (Spearman's rank coefficient 0.53121; p < 0.05). No patient experienced seizure deterioration and four patients reported remission of npS. This case-cohort study provides evidence that ANT-DBS interrupts sleep in a voltage-dependent manner, thus putatively resulting in an increase of npS. Reduction of nocturnal DBS voltage seems to lead to improvement of npS without hampering efficacy of ANT-DBS. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study.

PubMed

Witt, Karsten; Daniels, Christine; Reiff, Julia; Krack, Paul; Volkmann, Jens; Pinsker, Markus O; Krause, Martin; Tronnier, Volker; Kloss, Manja; Schnitzler, Alfons; Wojtecki, Lars; Bötzel, Kai; Danek, Adrian; Hilker, Rüdiger; Sturm, Volker; Kupsch, Andreas; Karner, Elfriede; Deuschl, Günther

2008-07-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. 156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohen's d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. German Federal Ministry of Education and Research (01GI0201).

Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease

PubMed Central

Zrinzo, L.; Martinez-Torres, I.; Frost, E.; Pinto, S.; Foltynie, T.; Holl, E.; Petersen, E.; Roughton, M.; Hariz, M.I.; Limousin, P.

2011-01-01

Objective: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change. Methods: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. Results: Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2% ± 20.15% off-medication and 16.9% ± 21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6% ± 5.5% and 4.5% ± 8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. Conclusion: The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. Classification of evidence: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy. PMID:21068426

The PROTICdb database for 2-DE proteomics.

PubMed

Langella, Olivier; Zivy, Michel; Joets, Johann

2007-01-01

PROTICdb is a web-based database mainly designed to store and analyze plant proteome data obtained by 2D polyacrylamide gel electrophoresis (2D PAGE) and mass spectrometry (MS). The goals of PROTICdb are (1) to store, track, and query information related to proteomic experiments, i.e., from tissue sampling to protein identification and quantitative measurements; and (2) to integrate information from the user's own expertise and other sources into a knowledge base, used to support data interpretation (e.g., for the determination of allelic variants or products of posttranslational modifications). Data insertion into the relational database of PROTICdb is achieved either by uploading outputs from Mélanie, PDQuest, IM2d, ImageMaster(tm) 2D Platinum v5.0, Progenesis, Sequest, MS-Fit, and Mascot software, or by filling in web forms (experimental design and methods). 2D PAGE-annotated maps can be displayed, queried, and compared through the GelBrowser. Quantitative data can be easily exported in a tabulated format for statistical analyses with any third-party software. PROTICdb is based on the Oracle or the PostgreSQLDataBase Management System (DBMS) and is freely available upon request at http://cms.moulon.inra.fr/content/view/14/44/.

Effect of temperature and initial dibutyl sulfide concentration in chloroform on its oxidation rate by ozone.

PubMed

Popiel, Stanisław; Nalepa, Tomasz; Dzierzak, Dorota; Stankiewicz, Romuald; Witkiewicz, Zygfryd

2008-09-15

A scheme of dibutyl sulfide (DBS) oxidation with ozone and generation of transitional products was determined in this study. The main identified intermediate product was dibutyl sulfoxide (DBSO), and the main end product of DBS oxidation was dibutyl sulfone (DBSO2). It was determined that for three temperatures: 0, 10 and 20 degrees C there was certain initial DBS concentration for which half-times observed in experimental conditions were equal and independent from temperature. Generation of phosgene and water as by-products was confirmed for the reaction of DBS with ozone in chloroform. Results of the described study allowed to present generalized mechanism of sulfide oxidation with ozone.

[Deep brain stimulation in parkinsonian patients with dopa intolerance].

PubMed

García-Ruiz, Pedro J; Feliz-Feliz, Cici; Ayerbe Gracia, Joaquín; Matías Arbelo, José; Salvador, Carlos; Val Fernández, Javier Del; García-Caldentey, Juan

2017-10-28

Deep brain stimulation (DBS) is at present, a useful treatment for patients with advanced Parkinson's disease and motor complications. The crucial step toward consistent DBS outcomes remains careful patient selection; several conditions must be fulfilled including excellent levo dopa response. We report two cases of early onset Parkinson's disease with severe intolerance to levo dopa but excellent and sustained response to DBS. DBS can be a useful alternative for parkinsonian patients with severe intolerance to levo dopa, provided a positive acute response to levo dopa or apomorphine is obtained. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

PubMed Central

Rossi, P. Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J.; Elias, W. Jeff; Rossi, Marvin A.; Butson, Christopher L.; Fox, Michael D.; McIntyre, Cameron C.; Pouratian, Nader; Swann, Nicole C.; de Hemptinne, Coralie; Gross, Robert E.; Chizeck, Howard J.; Tagliati, Michele; Lozano, Andres M.; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L.; Akbar, Umer; Gerhardt, Greg A.; Grill, Warren M.; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H.; Lang, Anthony E.; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y.; Molina, Rene; Opri, Enrico; Otto, Kevin J.; Oweiss, Karim G.; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A.; Shih, Ludy C.; Steinke, G. Karl; Tröster, Alexander I.; Vanegas, Nora; Zaghloul, Kareem A.; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D.; Okun, Michael S.

2016-01-01

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies. PMID:27092042

Utilizing a TDRS satellite for direct broadcast satellite-radio propagation experiments and demonstrations

NASA Technical Reports Server (NTRS)

Hollansworth, James E.

1993-01-01

The NASA/VOA Direct Broadcast Satellite-Radio (DBS-R) Program will be using a NASA Tracking Data Relay Satellite (TDRS) satellite at 62 deg. West longitude to conduct live satellite S-band propagation experiments and demonstrations of satellite sound broadcasting over the next two years (1993-1994). The NASA/VOA DBS-R program has applied intensive effort to garner domestic and international support for the DBS-R concept. An S-band DBS-R allocation was achieved for Region 2 at WARC-92 held in Spain. With this allocation, the DBS-R program now needs to conduct S-band propagation experiments and systems demonstrations that will assist in the development of planning approaches for the use of Broadcast Satellite Service (Sound) frequency bands prior to the planning conference called for by WARC-92. These activities will also support receiver concept development applied to qualities ranging from AM to Monophonic FM, Stereophonic FM, Monophonic CD, and Stereophonic CD quality.

Medical Management of Parkinson's Disease after Initiation of Deep Brain Stimulation.

PubMed

Fasano, Alfonso; Appel-Cresswell, Silke; Jog, Mandar; Zurowkski, Mateusz; Duff-Canning, Sarah; Cohn, Melanie; Picillo, Marina; Honey, Christopher R; Panisset, Michel; Munhoz, Renato Puppi

2016-09-01

In this review, we have gathered all the available evidence to guide medication management after deep brain stimulation (DBS) in Parkinson's disease (PD). Surprisingly, we found that almost no study addressed drug-based management in the postoperative period. Dopaminergic medications are usually reduced, but whether the levodopa or dopamine agonist is to be reduced is left to the personal preference of the treating physician. We have summarized the pros and cons of both approaches. No study on the management of cognitive problems after DBS has been done, and only a few studies have explored the pharmacological management of such DBS-resistant symptoms as voice (amantadine), balance (donepezil) or gait disorders (amantadine, methylphenidate). As for the psychiatric problems so frequently reported in PD patients, researchers have directed their attention to the complex interplay between stimulation and reduction of dopaminergic drugs only recently. In conclusion, studies addressing medical management following DBS are still needed and will certainly contribute to the ultimate success of DBS procedures.

Becoming more oneself? Changes in personality following DBS treatment for psychiatric disorders: Experiences of OCD patients and general considerations

PubMed Central

Rietveld, Erik; Stokhof, Martin; Denys, Damiaan

2017-01-01

Does DBS change a patient’s personality? This is one of the central questions in the debate on the ethics of treatment with Deep Brain Stimulation (DBS). At the moment, however, this important debate is hampered by the fact that there is relatively little data available concerning what patients actually experience following DBS treatment. There are a few qualitative studies with patients with Parkinson’s disease and Primary Dystonia and some case reports, but there has been no qualitative study yet with patients suffering from psychiatric disorders. In this paper, we present the experiences of 18 patients with Obsessive-Compulsive Disorder (OCD) who are undergoing treatment with DBS. We will also discuss the inherent difficulties of how to define and assess changes in personality, in particular for patients with psychiatric disorders. We end with a discussion of the data and how these shed new light on the conceptual debate about how to define personality. PMID:28426824

Direct broadcast satellite-radio market, legal, regulatory, and business considerations

NASA Technical Reports Server (NTRS)

Sood, Des R.

1991-01-01

A Direct Broadcast Satellite-Radio (DBS-R) System offers the prospect of delivering high quality audio broadcasts to large audiences at costs lower than or comparable to those incurred using the current means of broadcasting. The maturation of mobile communications technologies, and advances in microelectronics and digital signal processing now make it possible to bring this technology to the marketplace. Heightened consumer interest in improved audio quality coupled with the technological and economic feasibility of meeting this demand via DBS-R make it opportune to start planning for implementation of DBS-R Systems. NASA-Lewis and the Voice of America as part of their on-going efforts to improve the quality of international audio broadcasts, have undertaken a number of tasks to more clearly define the technical, marketing, organizational, legal, and regulatory issues underlying implementation of DBS-R Systems. The results and an assessment is presented of the business considerations underlying the construction, launch, and operation of DBS-R Systems.

Informed Consent Decision-Making in Deep Brain Stimulation.

PubMed

Mandarelli, Gabriele; Moretti, Germana; Pasquini, Massimo; Nicolò, Giuseppe; Ferracuti, Stefano

2018-05-11

Deep brain stimulation (DBS) has proved useful for several movement disorders (Parkinson’s disease, essential tremor, dystonia), in which first and/or second line pharmacological treatments were inefficacious. Initial evidence of DBS efficacy exists for refractory obsessive-compulsive disorder, treatment-resistant major depressive disorder, and impulse control disorders. Ethical concerns have been raised about the use of an invasive surgical approach involving the central nervous system in patients with possible impairment in cognitive functioning and decision-making capacity. Most of the disorders in which DBS has been used might present with alterations in memory, attention, and executive functioning, which may have an impact on the mental capacity to give informed consent to neurosurgery. Depression, anxiety, and compulsivity are also common in DBS candidate disorders, and could also be associated with an impaired capacity to consent to treatment or clinical research. Despite these issues, there is limited empirical knowledge on the decision-making levels of these patients. The possible informed consent issues of DBS will be discussed by focusing on the specific treatable diseases.

Embedded Carbide-derived Carbon (CDC) particles in polypyrrole (PPy) for linear actuator

NASA Astrophysics Data System (ADS)

Zondaka, Zane; Valner, Robert; Aabloo, Alvo; Tamm, Tarmo; Kiefer, Rudolf

2016-04-01

Conducting polymer linear actuators, for example sodium dodecylbenzenesulfonate (NaDBS) doped polypyrrole (PPy/DBS), have shown moderate strain and stress. The goal of this work was to increase the obtainable strain and stress by adding additional active material to PPy/DBS. In recent year's carbide-derived carbon (CDC)-based materials have been applied in actuators; however, the obtained displacement and actuation speed has been low comparing to conducting polymer based actuators. In the present work, a CDC-PPy hybrid was synthesized electrochemically and polyoxometalate (POM) - phosphotungstic acid - was used to attach charge to CDC particles. The CDC-POM served in the presence of NaDBS as an additional electrolyte. Cyclic voltammetry and chronopotentiometric electrochemomechanical deformation (ECMD) measurements were performed in Lithium bis(trifluoromethanesulfonyl)- imide (LiTFSI) aqueous electrolyte. The ECMD measurements revealed that the hybrid CDC-PPy material exhibited higher force and strain in comparison to PPy/DBS films. The new material was investigated by scanning electron microscopy (SEM) to evaluate CDC particle embedding in the polymer network.

An Overview of the Clinical Use of Filter Paper in the Diagnosis of Tropical Diseases

PubMed Central

Smit, Pieter W.; Elliott, Ivo; Peeling, Rosanna W.; Mabey, David; Newton, Paul N.

2014-01-01

Tropical infectious diseases diagnosis and surveillance are often hampered by difficulties of sample collection and transportation. Filter paper potentially provides a useful medium to help overcome such problems. We reviewed the literature on the use of filter paper, focusing on the evaluation of nucleic acid and serological assays for diagnosis of infectious diseases using dried blood spots (DBS) compared with recognized gold standards. We reviewed 296 eligible studies and included 101 studies evaluating DBS and 192 studies on other aspects of filter paper use. We also discuss the use of filter paper with other body fluids and for tropical veterinary medicine. In general, DBS perform with sensitivities and specificities similar or only slightly inferior to gold standard sample types. However, important problems were revealed with the uncritical use of DBS, inappropriate statistical analysis, and lack of standardized methodology. DBS have great potential to empower healthcare workers by making laboratory-based diagnostic tests more readily accessible, but additional and more rigorous research is needed. PMID:24366501

Direct broadcast satellite-radio market, legal, regulatory, and business considerations

NASA Astrophysics Data System (ADS)

Sood, Des R.

1991-03-01

A Direct Broadcast Satellite-Radio (DBS-R) System offers the prospect of delivering high quality audio broadcasts to large audiences at costs lower than or comparable to those incurred using the current means of broadcasting. The maturation of mobile communications technologies, and advances in microelectronics and digital signal processing now make it possible to bring this technology to the marketplace. Heightened consumer interest in improved audio quality coupled with the technological and economic feasibility of meeting this demand via DBS-R make it opportune to start planning for implementation of DBS-R Systems. NASA-Lewis and the Voice of America as part of their on-going efforts to improve the quality of international audio broadcasts, have undertaken a number of tasks to more clearly define the technical, marketing, organizational, legal, and regulatory issues underlying implementation of DBS-R Systems. The results and an assessment is presented of the business considerations underlying the construction, launch, and operation of DBS-R Systems.

Becoming more oneself? Changes in personality following DBS treatment for psychiatric disorders: Experiences of OCD patients and general considerations.

PubMed

de Haan, Sanneke; Rietveld, Erik; Stokhof, Martin; Denys, Damiaan

2017-01-01

Does DBS change a patient's personality? This is one of the central questions in the debate on the ethics of treatment with Deep Brain Stimulation (DBS). At the moment, however, this important debate is hampered by the fact that there is relatively little data available concerning what patients actually experience following DBS treatment. There are a few qualitative studies with patients with Parkinson's disease and Primary Dystonia and some case reports, but there has been no qualitative study yet with patients suffering from psychiatric disorders. In this paper, we present the experiences of 18 patients with Obsessive-Compulsive Disorder (OCD) who are undergoing treatment with DBS. We will also discuss the inherent difficulties of how to define and assess changes in personality, in particular for patients with psychiatric disorders. We end with a discussion of the data and how these shed new light on the conceptual debate about how to define personality.

Implementing DBS methodology for the determination of Compound A in monkey blood: GLP method validation and investigation of the impact of blood spreading on performance.

PubMed

Fan, Leimin; Lee, Jacob; Hall, Jeffrey; Tolentino, Edward J; Wu, Huaiqin; El-Shourbagy, Tawakol

2011-06-01

This article describes validation work for analysis of an Abbott investigational drug (Compound A) in monkey whole blood with dried blood spots (DBS). The impact of DBS spotting volume on analyte concentration was investigated. The quantitation range was between 30.5 and 10,200 ng/ml. Accuracy and precision of quality controls, linearity of calibration curves, matrix effect, selectivity, dilution, recovery and multiple stabilities were evaluated in the validation, and all demonstrated acceptable results. Incurred sample reanalysis was performed with 57 out of 58 samples having a percentage difference (versus the mean value) less than 20%. A linear relationship between the spotting volume and the spot area was drawn. The influence of spotting volume on concentration was discussed. All validation results met good laboratory practice acceptance requirements. Radial spreading of blood on DBS cards can be a factor in DBS concentrations at smaller spotting volumes.

Deep brain stimulation in the bed nucleus of the stria terminalis and medial forebrain bundle in a patient with major depressive disorder and anorexia nervosa.

PubMed

Blomstedt, Patric; Naesström, Matilda; Bodlund, Owe

2017-05-01

Deep brain stimulation (DBS) may be considered in severe cases of therapy-refractory major depressive disorder (MDD). However, DBS for MDD is still an experimental therapy. Therefore, it should only be administered in clinical studies driven by multidisciplinary teams, including surgeons with substantial experience of DBS in the treatment of other conditions.

Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

PubMed Central

Kent, Alexander R.; Grill, Warren M.

2012-01-01

Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

[Mental competence in the context of deep brain stimulation].

PubMed

Berghmans, R L P; De Wert, G M W R

2004-07-10

In a case of Parkinson's disease, the patient was treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). STN-DBS affected the mental competence of the patient and ethical questions were raised about the decision as to the direction of further treatment. The patient was asked for his opinion on the therapeutic options during a phase of non-stimulation and chose to be stimulated and admitted to a psychiatric hospital because of mental incompetence rather than remaining unstimulated, mentally competent but bedridden. Developments in the neurosciences (including STN-DBS) raise a number of different fundamental (theoretical and philosophical) as well as practical questions. STN-DBS can have various unintended (behavioural) effects. In the case presented, more weight was rightly given to the mental competence of the unstimulated patient, although comments can be made with regard to his decision making, as his choice was made in a phase of serious distress. Attention is paid to the relevance of a so-called self-binding directive. STN-DBS is not morally neutral and the case involves a tragic dilemma: a conflict between irreconcilable duties for the physician. The further development and proliferation of STN-DBS requires caution and moral deliberation. It remains important to search for alternative treatment strategies with less undesirable side effects.

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

PubMed Central

Nowak, Karl; Mix, Eilhard; Gimsa, Jan; Strauss, Ulf; Sriperumbudur, Kiran Kumar; Benecke, Reiner; Gimsa, Ulrike

2011-01-01

Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation. PMID:21603182

Swallowing Quality of Life After Zona Incerta Deep Brain Stimulation.

PubMed

Sundstedt, Stina; Nordh, Erik; Linder, Jan; Hedström, Johanna; Finizia, Caterina; Olofsson, Katarina

2017-02-01

The management of Parkinson's disease (PD) has been improved, but management of signs like swallowing problems is still challenging. Deep brain stimulation (DBS) alleviates the cardinal motor symptoms and improves quality of life, but its effect on swallowing is not fully explored. The purpose of this study was to examine self-reported swallowing-specific quality of life before and after caudal zona incerta DBS (cZI DBS) in comparison with a control group. Nine PD patients (2 women and 7 men) completed the self-report Swallowing Quality of Life questionnaire (SWAL-QOL) before and 12 months after cZI DBS surgery. The postoperative data were compared to 9 controls. Median ages were 53 years (range, 40-70 years) for patients and 54 years (range, 42-72 years) for controls. No significant differences were found between the pre- or postoperative scores. The SWAL-QOL total scores did not differ significantly between PD patients and controls. The PD patients reported significantly lower scores in the burden subscale and the symptom scale. Patients with PD selected for cZI DBS showed good self-reported swallowing-specific quality of life, in many aspects equal to controls. The cZI DBS did not negatively affect swallowing-specific quality of life in this study.

Criticisms biologically unwarranted and analytically irrelevant: Reply to Rominger et al.

USGS Publications Warehouse

Bender, L.C.; Weisenberger, M.E.

2009-01-01

The criticisms of Rominger et al. (2008) of our retrospective analysis of desert bighorn sheep (DBS; Ovis canadensis mexicana) dynamics in the San Andres Mountains of south-central New Mexico, USA, contained many biological errors and analytical oversights. Herein, we show that Rominger et al. (2008) 1) overstated both magnitude and potential effect of predator removal; 2) incorrectly claimed that our total precipitation (TP) model did not fit the data when TP correctly classed ???66 of subsequent population increases and declines (P ??? 0.063); 3) presented a necessary prerequisite of the exponential model (serial correlation between Nt and Nt1) as the key relationship in the DBS data, when it merely reflected that DBS are strongly K-selected and was irrelevant to our hypothesis tests specific to factors affecting the instantaneous rate of population increase (r); 4) greatly oversimplified relationships among precipitation, arid environments, and DBS; and 5) advocated a time for collection of lamb/female (L/F) ratio data that was unrelated to any meaningful period in the biological year of DBS and consequently presented L/F ratio data unrelated to observed dynamics of DBS. In contrast, the L/F ratios used in Bender and Weisenberger (2005) correctly predicted annual changes and were correlated with long-term population rates of change.

Deep brain stimulation of the nucleus accumbens shell attenuates cue-induced reinstatement of both cocaine and sucrose seeking in rats.

PubMed

Guercio, Leonardo A; Schmidt, Heath D; Pierce, R Christopher

2015-03-15

Stimuli previously associated with drug taking can become triggers that can elicit craving and lead to relapse of drug-seeking behavior. Here, we examined the influence of deep brain stimulation (DBS) in the nucleus accumbens shell on cue-induced reinstatement of cocaine seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.254 mg, i.v.) for 2 h daily for 21 days, with each infusion of cocaine being paired with a cue light. After 21 days of self-administration, cocaine-taking behavior was extinguished by replacing cocaine with saline in the absence of the cue light. Next, during the reinstatement phase, DBS was administered bilaterally into the nucleus accumbens shell through bipolar stainless steel electrodes immediately prior to re-exposure to cues previously associated with cocaine reinforcement. DBS continued throughout the 2 h reinstatement session. Parallel studies examined the influence of accumbens shell DBS on reinstatement induced by cues previously associated with sucrose reinforcement. Results indicated that DBS of the nucleus accumbens shell significantly attenuated cue-induced reinstatement of cocaine and sucrose seeking. Together, these results indicate that DBS of the accumbens shell disrupts cue-induced reinstatement associated with both a drug and a natural reinforcer. Copyright © 2014 Elsevier B.V. All rights reserved.

Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease

PubMed Central

Cantin, Léo; Prud'Homme, Michel; Langlois, Mélanie

2015-01-01

Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD. PMID:26558134

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

PubMed Central

Mace, Michael; Pavese, Nicola; Borisyuk, Roman; Bain, Peter

2017-01-01

Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit. PMID:28068428

Automated system for on-line desorption of dried blood spots applied to LC/MS/MS pharmacokinetic study of flurbiprofen and its metabolite.

PubMed

Déglon, Julien; Thomas, Aurélien; Daali, Youssef; Lauer, Estelle; Samer, Caroline; Desmeules, Jules; Dayer, Pierre; Mangin, Patrice; Staub, Christian

2011-01-25

This paper illustrates the development of an automated system for the on-line bioanalysis of dried blood spots (on-line DBS). In this way, a prototype was designed for integration into a conventional LC/MS/MS, allowing the successive extraction of 30 DBS toward the analytical system without any sample pretreatment. The developed method was assessed for the DBS analysis of flurbiprofen (FLB) and its metabolite 4-hydroxyflurbiprofen (OH-FLB) in human whole blood (i.e. 5 μL). The automated procedure was fully validated based on international criteria and showed good precision, trueness, and linearity over the expected concentration range (from 10 to 1000 ng/mL and 100 to 10,000 ng/mL for OH-FLB and FLB respectively). Furthermore, the prototype showed good results in terms of recovery and carry-over. Stability of both analytes on filter paper was also investigated and the results suggested that DBS could be stored at ambient temperature for over 1 month. The on-line DBS automated system was then successfully applied to a pharmacokinetic study performed on healthy male volunteers after oral administration of a single 50-mg dose of FLB. Additionally, a comparison between finger capillary DBS and classic venous plasma concentrations was investigated. A good correlation was observed, demonstrating the complementarity of both sampling forms. The automated system described in this article represents an efficient tool for the LC/MS/MS analysis of DBS samples in many bioanalytical applications. Copyright © 2010 Elsevier B.V. All rights reserved.

Mental Health-Related Healthcare Use Following Bilateral Deep Brain Stimulation For Parkinson's Disease.

PubMed

Westbay, Lauren C; Cao, Lishan; Burnett-Zeigler, Inger; Reizine, Natalie; Barton, Brandon; Ippolito, Dolores; Weaver, Frances M; Stroupe, Kevin T

2015-01-01

The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are both effective targets for deep brain stimulation (DBS) to relieve motor symptoms of Parkinson's disease. However, studies have reported varied effects on mental health-related adverse events and depressed mood following DBS. The current observational study sought to compare mental health healthcare utilization and costs for three years following STN or GPi DBS. For a cohort of Veterans (n = 161) with Parkinson's disease who participated in a larger multi-site randomized trial, we compared mental health outpatient visits, medication use, inpatient admissions, and associated costs by DBS target site (STN vs. GPi). Neither group nor time differences were significant for mental health outpatient or inpatient utilization following DBS. Overall costs associated with mental health visits and medications did not differ by time or by group. However, the percentage of patients with mental health medication use increased in the 6-month and 6 to 12 month periods post-surgery. The STN group had significantly greater increase in medication use at 6 to 12 months post-surgery compared to the GPi group (p <  0.05). Despite a brief increase in medication use following surgery, this study suggests that mental health healthcare use and costs are stable over time and similar between DBS targets. Prior research findings of mental health-related adverse events and mood following DBS did not translate to greater mental health service utilization in our cohort. The changes seen in the year following surgery may reflect temporary adjustments with stabilization over time.

A Computerized Microelectrode Recording to Magnetic Resonance Imaging Mapping System for Subthalamic Nucleus Deep Brain Stimulation Surgery.

PubMed

Dodani, Sunjay S; Lu, Charles W; Aldridge, J Wayne; Chou, Kelvin L; Patil, Parag G

2018-06-01

Accurate electrode placement is critical to the success of deep brain stimulation (DBS) surgery. Suboptimal targeting may arise from poor initial target localization, frame-based targeting error, or intraoperative brain shift. These uncertainties can make DBS surgery challenging. To develop a computerized system to guide subthalamic nucleus (STN) DBS electrode localization and to estimate the trajectory of intraoperative microelectrode recording (MER) on magnetic resonance (MR) images algorithmically during DBS surgery. Our method is based upon the relationship between the high-frequency band (HFB; 500-2000 Hz) signal from MER and voxel intensity on MR images. The HFB profile along an MER trajectory recorded during surgery is compared to voxel intensity profiles along many potential trajectories in the region of the surgically planned trajectory. From these comparisons of HFB recordings and potential trajectories, an estimate of the MER trajectory is calculated. This calculated trajectory is then compared to actual trajectory, as estimated by postoperative high-resolution computed tomography. We compared 20 planned, calculated, and actual trajectories in 13 patients who underwent STN DBS surgery. Targeting errors for our calculated trajectories (2.33 mm ± 0.2 mm) were significantly less than errors for surgically planned trajectories (2.83 mm ± 0.2 mm; P = .01), improving targeting prediction in 70% of individual cases (14/20). Moreover, in 4 of 4 initial MER trajectories that missed the STN, our method correctly indicated the required direction of targeting adjustment for the DBS lead to intersect the STN. A computer-based algorithm simultaneously utilizing MER and MR information potentially eases electrode localization during STN DBS surgery.

Rapid Modulation of Protein Expression in the Rat Hippocampus Following Deep Brain Stimulation of the Fornix.

PubMed

Gondard, Elise; Chau, Hien N; Mann, Amandeep; Tierney, Travis S; Hamani, Clement; Kalia, Suneil K; Lozano, Andres M

2015-01-01

The forniceal area is currently being evaluated as a target for deep brain stimulation (DBS) to improve cognitive function in patients with Alzheimer's disease. The molecular changes at downstream targets within the stimulated circuit are unknown. To analyze the modulation of hippocampal protein expression following 1 h of fornix DBS in the rat. Animals underwent bilateral forniceal DBS for 1 h and sacrificed at different time-points after the initiation of the stimulation (1 h, 2.5 h, 5 h, 25 h). Bilateral hippocampi were isolated for western blot analyses. Forniceal DBS led to a dramatic elevation of cFos post-stimulation, suggesting that forniceal DBS activates the hippocampus. There was also a significant increase in candidate proteins including several trophic factors, such as brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) but not glial cell-derived neurotrophic factor (GDNF). There was in addition, increased expression of the synaptic markers growth associated protein 43 (GAP-43), synaptophysin and α-synuclein. No changes were observed at the studied time-points in Alzheimer's-related proteins including amyloid precursor protein (APP), tau, phosphorylated tau (ptau), or selected chaperone proteins (HSP40, HSP70 and CHIP). Forniceal DBS triggers hippocampal activity and rapidly modulate the expression of neurotrophic factors and markers of synaptic plasticity known to play key roles in memory processing. The clinical effects of DBS of the fornix may, in part, be mediated by producing changes in the expression of these proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

PubMed

Phillips, Lara; Litcofsky, Kaitlyn A; Pelster, Michael; Gelfand, Matthew; Ullman, Michael T; Charles, P David

2012-01-01

Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated.

Computational modeling of pedunculopontine nucleus deep brain stimulation

NASA Astrophysics Data System (ADS)

Zitella, Laura M.; Mohsenian, Kevin; Pahwa, Mrinal; Gloeckner, Cory; Johnson, Matthew D.

2013-08-01

Objective. Deep brain stimulation (DBS) near the pedunculopontine nucleus (PPN) has been posited to improve medication-intractable gait and balance problems in patients with Parkinson's disease. However, clinical studies evaluating this DBS target have not demonstrated consistent therapeutic effects, with several studies reporting the emergence of paresthesia and oculomotor side effects. The spatial and pathway-specific extent to which brainstem regions are modulated during PPN-DBS is not well understood. Approach. Here, we describe two computational models that estimate the direct effects of DBS in the PPN region for human and translational non-human primate (NHP) studies. The three-dimensional models were constructed from segmented histological images from each species, multi-compartment neuron models and inhomogeneous finite element models of the voltage distribution in the brainstem during DBS. Main Results. The computational models predicted that: (1) the majority of PPN neurons are activated with -3 V monopolar cathodic stimulation; (2) surgical targeting errors of as little as 1 mm in both species decrement activation selectivity; (3) specifically, monopolar stimulation in caudal, medial, or anterior PPN activates a significant proportion of the superior cerebellar peduncle (up to 60% in the human model and 90% in the NHP model at -3 V) (4) monopolar stimulation in rostral, lateral or anterior PPN activates a large percentage of medial lemniscus fibers (up to 33% in the human model and 40% in the NHP model at -3 V) and (5) the current clinical cylindrical electrode design is suboptimal for isolating the modulatory effects to PPN neurons. Significance. We show that a DBS lead design with radially-segmented electrodes may yield improved functional outcome for PPN-DBS.

Characterization of oscillatory changes in hippocampus and amygdala after deep brain stimulation of the infralimbic prefrontal cortex.

PubMed

Cervera-Ferri, Ana; Teruel-Martí, Vicent; Barceló-Molina, Moises; Martínez-Ricós, Joana; Luque-García, Aina; Martínez-Bellver, Sergio; Adell, Albert

2016-07-01

Deep brain stimulation (DBS) is a new investigational therapy that has generated positive results in refractory depression. Although the neurochemical and behavioral effects of DBS have been examined, less attention has been paid to the influence of DBS on the network dynamics between different brain areas, which could contribute to its therapeutic effects. Herein, we set out to identify the effects of 1 h DBS in the infralimbic cortex (IL) on the oscillatory network dynamics between hippocampus and basolateral amygdala (BLA), two regions implicated in depression and its treatment. Urethane-anesthetized rats with bilaterally implanted electrodes in the IL were exposed to 1 h constant stimulation of 130 Hz of frequency, 60 μA of constant current intensity and biphasic pulse width of 80 μsec. After a period of baseline recording, local field potentials (LFP) were recorded with formvar-insulated stainless steel electrodes. DBS of the IL increased the power of slow wave (SW, <1.5 Hz) and theta (3-12 Hz) frequencies in the hippocampus and BLA Furthermore, IL DBS caused a precise coupling in different frequency bands between both brain structures. The increases in SW band synchronization in hippocampus and BLA after DBS suggest that these changes may be important for the improvement of depressive behavior. In addition, the augmentation in theta synchrony might contribute to improvement in emotional and cognitive processes. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Subthalamic Nucleus Deep Brain Stimulation Impacts Language in Early Parkinson's Disease

PubMed Central

Phillips, Lara; Litcofsky, Kaitlyn A.; Pelster, Michael; Gelfand, Matthew

2012-01-01

Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated. PMID:22880117

Perspective on the Economic Evaluation of Deep Brain Stimulation

PubMed Central

McIntosh, Emma Sarah

2011-01-01

Parkinson's disease (PD) is an example of a disease area experiencing increasing use of deep brain stimulation (DBS) to treat symptoms. PD is a major cause of morbidity and has a substantial economic impact on the patients, their caregivers, the health service, and broader social and community services. The PDSURG Collaborators Group reported that DBS surgery for patients with advanced PD improves motor function and quality of life that medical therapy alone at 1 year but there are surgery related side effects in a minority (Williams et al., 2010). The aim of this paper however is to build upon the knowledge generated from evaluating DBS in PD and to provide a detailed perspective on the economic evaluation of DBS more generally with a view to providing a framework for informative design of DBS economic evaluations. This perspective will outline the key categories of resource use pertinent to DBS beyond the surgical scenario and into the broader aspects of follow-up care, adverse events, repeat procedures, social and community care, patient and carer costs, and will explore the importance of handling capital costs of DBS equipment appropriately as well as including costs occurring in the future. In addition, this perspective article will outline the importance of capturing broader aspects of “outcome” or benefits as compared to those traditional clinical measures used. The key message is the importance of employing a broad “perspective” on the measurement and valuation of costs and benefits as well as the importance of adopting the appropriate time horizon for evaluating the costs and benefits of DBS. In order to do this effectively it may be that alternative methods of economic evaluation in health care to the commonly used cost-effectiveness analysis may have to be used, such as cost-benefit analysis (McIntosh et al., 2010). PMID:21779238

Molecular transport machinery involved in orchestrating luminal acid-induced duodenal bicarbonate secretion in vivo

PubMed Central

Singh, Anurag Kumar; Liu, Yongjian; Riederer, Brigitte; Engelhardt, Regina; Thakur, Basant Kumar; Soleimani, Manoocher; Seidler, Ursula

2013-01-01

The duodenal villus brush border membrane expresses several ion transporters and/or channels, including the solute carrier 26 anion transporters Slc26a3 (DRA) and Slc26a6 (PAT-1), the Na+/H+ exchanger isoform 3 (NHE3), as well as the anion channels cystic fibrosis transmembrane conductance regulator (CFTR) and Slc26a9. Using genetically engineered mouse models lacking Scl26a3, Slc26a6, Slc26a9 or Slc9a3 (NHE3), the study was carried out to assess the role of these transporters in mediating the protective duodenal bicarbonate secretory response (DBS-R) to luminal acid; and to compare it to their role in DBS-R elicited by the adenylyl cyclase agonist forskolin. While basal DBS was reduced in the absence of any of the three Slc26 isoforms, the DBS-R to forskolin was not altered. In contrast, the DBS-R to a 5 min exposure to luminal acid (pH 2.5) was strongly reduced in the absence of Slc26a3 or Slc26a9, but not Slc26a6. CFTR inhibitor [CFTR(Inh)-172] reduced the first phase of the acid-induced DBS-R, while NHE3 inhibition (or knockout) abolished the sustained phase of the DBS-R. Luminal acid exposure resulted in the activation of multiple intracellular signalling pathways, including SPAK, AKT and p38 phosphorylation. It induced a biphasic trafficking of NHE3, first rapidly into the brush border membrane, followed by endocytosis in the later stage. We conclude that the long-lasting DBS-R to luminal acid exposure activates multiple duodenocyte signalling pathways and involves changes in trafficking and/or activity of CFTR, Slc26 isoforms Slc26a3 and Slc26a9, and NHE3. PMID:24018950

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact.

PubMed

Kent, A R; Grill, W M

2012-06-01

The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease.

PubMed

Karimi, M; Golchin, N; Tabbal, S D; Hershey, T; Videen, T O; Wu, J; Usche, J W M; Revilla, F J; Hartlein, J M; Wernle, A R; Mink, J W; Perlmutter, J S

2008-10-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease

PubMed Central

Karimi, M.; Golchin, N.; Tabbal, S. D.; Hershey, T.; Videen, T. O.; Wu, J.; Usche, J. W. M.; Revilla, F. J.; Hartlein, J. M.; Wernle, A. R.; Mink, J. W.

2008-01-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (rs = –0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (rs = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (rs = –0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease. PMID:18697909

Dried blood spot HIV-1 RNA quantification: A useful tool for viral load monitoring among HIV-infected individuals in India

PubMed Central

Neogi, Ujjwal; Gupta, Soham; Rodridges, Rashmi; Sahoo, Pravat Nalini; Rao, Shwetha D.; Rewari, Bharat B.; Shastri, Suresh; De Costa, Ayesha; Shet, Anita

2012-01-01

Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (−0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally. PMID:23391790

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID:24074493

Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

PubMed

Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

2016-01-13

Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN-DBS with TMS at short (∼ 3 ms) and medium (∼ 23 ms) intervals increased cortical excitability that lasted for up to 45 min, whereas the control condition (fixed latency of 167 ms) had no effects on cortical excitability. This is the first demonstration of associative plasticity in the STN-M1 circuits in PD patients using this novel technique. The potential therapeutic effects of combining DBS and noninvasive cortical stimulation should be investigated further. Copyright © 2016 the authors 0270-6474/16/360397-09$15.00/0.

Study of cataclastic deformation in compressive tectonic regime of a sandstone from south central Pyrenees, Spain: Timing of deformation bands occurrence during burial history and comparison with geomechanical models.

NASA Astrophysics Data System (ADS)

Robert, Romain; Robion, Philippe; David, Christian; Souloumiac, Pauline; Saillet, Elodie

2017-04-01

In high porosity sandstone lithologies, deformation bands (DBs) are characterized by changes in micro-structural characteristics inducing a localized change in the petrophysical properties of the rock. These DBs, which are generally tabular structures from millimeters to few centimeters thick, can be used at the field scale to decipher extensional or compactional tectonic regime. However, numerous parameters in addition to the tectonic regime may affect development of DBs, and particularly the evolution of porosity during burial history. The aim of this work is to understand the relationship between the DBs occurrence in tectonic shortening regime and the timing of grain cementation that occurs during burial for an analogue to siliciclastic reservoir. For that purpose, we have focused our analysis on the Aren syn-tectonic sandstone formation, maastrichtian in age, localized on the front of the Boixols thrust, on the southern side of the Sant Corneli anticline, in the south central Pyrenees (Spain). The outcrops are localized in the Tremp-Graus basin, all along a 30 km East-West trend where 10 different sites, in which deformation bands are observable, have been investigated and sampled. The structural geometry of the basin is constrained with 3 serial N-S oriented cross sections showing an increase of the shortening from West to East. Our field work strategy was to, 1) measure the orientation of the DBs in each site, 2) take cores both within the DBs and the host rock to conduct systematic thin section investigations, and 3) take oriented cores in order to study the magnetic fabric giving informations on the internal deformation linked to a set of deformation band and regional N-S shortening. Field data show a minimum of two sets of DBs on each site with variation of orientations and densities. These DBs are perpendicular to the strata which prove their early occurrence, recording the initial stages of local deformation and evolution of the Boixols fold and thrust. At the microstructures scale, DBs are characterized by grain crushing with hertzian fractures associated with pore collapse. All these evidences allow us to define these structures as compaction bands. Further microscopical investigation, grain size distribution and initial porosity are determined by image analysis. These data are confronted to geomechanical models in order to investigate the relationship between the occurrences of DBs in the burial history and the diagenesis of the rock during the compressive event.

High Temperature Characteristics of Pt/TaSi2/Pt/W and Pt/Ti/W Diffusion Barrier Systems for Ohmic Contacts to 4H-SiC

NASA Technical Reports Server (NTRS)

Okojie, Robert S.; Lukco, Dorothy

2017-01-01

The degradation of ohmic contacts to 4H-SiC pressure sensors over time at high temperature is primarily due to two failure mechanisms: migrating bond pad Au and atmospheric O toward the ohmic contact SiC interface and the inter-metallic mixing between diffusion barrier systems (DBS) and the underlying ohmic contact metallization. We investigated the effectiveness of Pt/TaSi2/Pt/W (DBS-A) and Pt/Ti/W (DBS-B) in preventing Au and O diffusion through the underlying binary Ti/W or alloyed W50:Ni50 ohmic contacts to 4H-SiC and the DBS ohmic contact intermixing at temperature up to 700 C.

[Deep brain stimulation in the treatment of movement disorders].

PubMed

Goto, Satoshi

2007-11-01

The introduction of deep brain stimulation (DBS) was a historical step forward for the treatment of advanced and medically intractable movement disorders that include Parkinson's disease, dystonias, essential tremor, and Holmes' tremor. DBS is able to modulate the target region electrically in a reversible and adjustable fashion in contrast to an irreversible and destructive lesioning procedure. In the treatment of movement disorders, the potential targets are the thalamic ventral intermediate nucleus (Vim), globus pallidus internus (GPi), subthalamic nucleus (STN), pedunculopontine nucleus (PPN), and thalamic Vo-complex nucleus. With the development of DBS technology and stereotactic neurosurgical techniques, its therapeutic efficacy has been increased while reducing surgical complications. DBS has become an established therapy for disabling movement disorders and is currently being used to treat neuropsychiatric disorders.

Correction for the Hematocrit Bias in Dried Blood Spot Analysis Using a Nondestructive, Single-Wavelength Reflectance-Based Hematocrit Prediction Method.

PubMed

Capiau, Sara; Wilk, Leah S; De Kesel, Pieter M M; Aalders, Maurice C G; Stove, Christophe P

2018-02-06

The hematocrit (Hct) effect is one of the most important hurdles currently preventing more widespread implementation of quantitative dried blood spot (DBS) analysis in a routine context. Indeed, the Hct may affect both the accuracy of DBS methods as well as the interpretation of DBS-based results. We previously developed a method to determine the Hct of a DBS based on its hemoglobin content using noncontact diffuse reflectance spectroscopy. Despite the ease with which the analysis can be performed (i.e., mere scanning of the DBS) and the good results that were obtained, the method did require a complicated algorithm to derive the total hemoglobin content from the DBS's reflectance spectrum. As the total hemoglobin was calculated as the sum of oxyhemoglobin, methemoglobin, and hemichrome, the three main hemoglobin derivatives formed in DBS upon aging, the reflectance spectrum needed to be unmixed to determine the quantity of each of these derivatives. We now simplified the method by only using the reflectance at a single wavelength, located at a quasi-isosbestic point in the reflectance curve. At this wavelength, assuming 1-to-1 stoichiometry of the aging reaction, the reflectance is insensitive to the hemoglobin degradation and only scales with the total amount of hemoglobin and, hence, the Hct. This simplified method was successfully validated. At each quality control level as well as at the limits of quantitation (i.e., 0.20 and 0.67) bias, intra- and interday imprecision were within 10%. Method reproducibility was excellent based on incurred sample reanalysis and surpassed the reproducibility of the original method. Furthermore, the influence of the volume spotted, the measurement location within the spot, as well as storage time and temperature were evaluated, showing no relevant impact of these parameters. Application to 233 patient samples revealed a good correlation between the Hct determined on whole blood and the predicted Hct determined on venous DBS. The bias obtained with Bland and Altman analysis was -0.015 and the limits of agreement were -0.061 and 0.031, indicating that the simplified, noncontact Hct prediction method even outperforms the original method. In addition, using caffeine as a model compound, it was demonstrated that this simplified Hct prediction method can effectively be used to implement a Hct-dependent correction factor to DBS-based results to alleviate the Hct bias.

Association of Deep Brain Stimulation Washout Effects With Parkinson Disease Duration

PubMed Central

Cooper, Scott E.; McIntyre, Cameron C.; Fernandez, Hubert H.; Vitek, Jerrold L.

2016-01-01

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves symptoms of Parkinson disease (PD), including bradykinesia. When stimulation ceases abruptly, bradykinesia returns gradually. The duration of the gradual, slow washout varies across patients, and although the origin of this variability is unclear, it is hypothesized to be related to 1 or more clinical characteristics of patients. Objective To determine if a correlation exists between clinical characteristics of patients with Parkinson disease (age, age at disease onset, disease severity, disease duration, medication dose, or time since surgery) and the washout rate for bradykinesia when STN DBS is discontinued. Design Serial quantitative assessments of bradykinesia were performed during a defined period following cessation of STN DBS. Setting Academic research. Patients Twenty-four patients with Parkinson disease who underwent STN DBS were enrolled in the study. Patients were assessed while off medication (medication had been discontinued 10½ to 16½ hours before testing), and stimulator settings were unchanged for a mean (median) of 20 (14) months. Main Outcome Measures We measured bradykinesia in the dominant hand by assessing finger tapping (item 23 on the Unified Parkinson Disease Rating Scale), which was quantified using an angular velocity transducer strapped on the index finger. Finger tapping was assessed every 2 minutes for 20 seconds at a time. This was performed during a 20-minute period with DBS on (baseline period), during a 50-minute period following discontinuation of STN DBS for the dominant hand, and again during a 20-minute period after turning on the device. Results When STN DBS was turned off, an initial fast but partial loss of benefit was observed, which was followed by a further slow washout of the residual therapeutic effect. The half-life of the slow washout phase varied significantly across patients, and this variation was strongly related to disease duration: patients with shorter disease duration experienced slower washout, while patients with longer disease duration experienced faster washout. Conclusions Washout of STN DBS effects varies with Parkinson disease duration. Estimates of proper washout time based on one patient population may not apply to populations with different disease durations. In DBS clinical trials, washout intervals should be chosen conservatively or adjusted for individual variation in the rate at which washout occurs. PMID:23070397

Dried blood spots for the enzymatic diagnosis of lysosomal storage diseases in dogs and cats.

PubMed

Sewell, Adrian C; Haskins, Mark E; Giger, Urs

2012-12-01

In people, lysosomal storage diseases (LSD) can be diagnosed by assaying enzyme activities in dried blood spots (DBS). The aim of this study was to evaluate the feasibility of using DBS samples from dogs and cats to measure lysosomal enzymatic activities and diagnose LSD. Drops of fresh whole blood collected in EDTA from dogs and cats with known or suspected LSD and from clinically healthy dogs and cats were placed on neonatal screening cards, dried, and mailed to the Metabolic Laboratory, University Children's Hospital, Frankfurt, Germany. Activities of selected lysosomal enzymes were measured using fluorescent substrates in a 2-mm diameter disk (~2.6 μL blood) punched from the DBS. Results were expressed as nmol substrate hydrolyzed per mL of blood per minute or hour. Reference values were established for several lysosomal enzyme activities in DBS from dogs and cats; for most enzymes, activities were higher than those published for human samples. Activities of β-glucuronidase, N-acetylglucosamine-4-sulfatase (arylsulfatase B), α-mannosidase, α-galactosidase, α-fucosidase, and hexosaminidase A were measureable in DBS from healthy cats and dogs; α-iduronidase activity was measureable only in cats. In samples from animals with LSD, markedly reduced activity of a specific enzyme was found. In contrast, in samples from cats affected with mucolipidosis II, activities of lysosomal enzymes were markedly increased. Measurement of lysosomal enzyme activities in DBS provides an inexpensive, simple, and convenient method to screen animals for suspected LSD and requires only a small sample volume. For diseases in which the relevant enzyme activity can be measured in DBS, a specific diagnosis can be made. © 2012 American Society for Veterinary Clinical Pathology.

An algorithm for management of deep brain stimulation battery replacements: devising a web-based battery estimator and clinical symptom approach.

PubMed

Montuno, Michael A; Kohner, Andrew B; Foote, Kelly D; Okun, Michael S

2013-01-01

Deep brain stimulation (DBS) is an effective technique that has been utilized to treat advanced and medication-refractory movement and psychiatric disorders. In order to avoid implanted pulse generator (IPG) failure and consequent adverse symptoms, a better understanding of IPG battery longevity and management is necessary. Existing methods for battery estimation lack the specificity required for clinical incorporation. Technical challenges prevent higher accuracy longevity estimations, and a better approach to managing end of DBS battery life is needed. The literature was reviewed and DBS battery estimators were constructed by the authors and made available on the web at http://mdc.mbi.ufl.edu/surgery/dbs-battery-estimator. A clinical algorithm for management of DBS battery life was constructed. The algorithm takes into account battery estimations and clinical symptoms. Existing methods of DBS battery life estimation utilize an interpolation of averaged current drains to calculate how long a battery will last. Unfortunately, this technique can only provide general approximations. There are inherent errors in this technique, and these errors compound with each iteration of the battery estimation. Some of these errors cannot be accounted for in the estimation process, and some of the errors stem from device variation, battery voltage dependence, battery usage, battery chemistry, impedance fluctuations, interpolation error, usage patterns, and self-discharge. We present web-based battery estimators along with an algorithm for clinical management. We discuss the perils of using a battery estimator without taking into account the clinical picture. Future work will be needed to provide more reliable management of implanted device batteries; however, implementation of a clinical algorithm that accounts for both estimated battery life and for patient symptoms should improve the care of DBS patients. © 2012 International Neuromodulation Society.

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact

PubMed Central

Kent, A R; Grill, W M

2012-01-01

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the selection of stimulus parameters is a clinical burden and often yields sub-optimal outcomes for patients. Measurement of electrically evoked compound action potentials (ECAPs) during DBS could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulus parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1,000 to 5,000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 μs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters. PMID:22510375

Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum.

PubMed

Mazzone, Paolo; Vilela Filho, Osvaldo; Viselli, Fabio; Insola, Angelo; Sposato, Stefano; Vitale, Flora; Scarnati, Eugenio

2016-07-01

The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region.

External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

PubMed

Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

2012-01-01

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

Skin complications in deep brain stimulation for Parkinson's disease: frequency, time course, and risk factors.

PubMed

Sixel-Döring, Friederike; Trenkwalder, Claudia; Kappus, Christoph; Hellwig, Dieter

2010-02-01

Deep brain stimulation (DBS) has been recognized as an efficacious treatment for movement disorders. Its beneficial effects however may be lost due to skin complications such as erosions or infections over the implanted foreign material. We sought to document skin complications in the entire Parkinson's disease patient population who received a DBS system at the Marburg/Kassel implantation centre since the start of our DBS program in January 2002 to analyze frequency, time course, and possible risk factors. We investigated 85 consecutive patients with Parkinson's disease (PD) from a single center/single surgeon DBS series for the occurrence of skin complications and analyzed localization, time course, and possible risk factors. Mean follow-up was 3 years (range 1-7 years). In total, 21/85 patients (24.7%) suffered a total of 30 single skin complications. Sixty percent of all incidents occurred within the first post-operative year. Forty percent of all incidents occurred later than the first year following primary implantation. Complications involved the burr hole cap in 37%, the course of the cables in 33%, and the impulse generator (IPG) site in 30%. Six of 21 patients suffered recurring skin complications. Eight patients permanently lost their DBS system. Factor analysis for age, gender, disease duration, disease severity, the incidence of hypertension or diabetes as well as a 2-day period with externalized electrodes for continuous test stimulation did not have any statistically significant impact on skin complications. We conclude that (1) PD patients have a risk for skin complications after DBS as long as the system remains in situ and (2) there are at present no identifiable risk factors for skin complications after DBS, other than PD itself.

Deep brain stimulation of the inferior colliculus: a possible animal model to study paradoxical kinesia observed in some parkinsonian patients?

PubMed

Melo-Thomas, Liana; Thomas, Uwe

2015-02-15

The inferior colliculus (IC) plays an important role in the normal processing of the acoustic message and is also involved in the filtering of acoustic stimuli of aversive nature. The neural substrate of the IC can also influence haloperidol-induced catalepsy. Considering that (i) paradoxical kinesia, observed in some parkinsonian patients, seems to be dependent of their emotional state and (ii) deep brain stimulation (DBS) represents an alternative therapeutic route for the relief of parkinsonian symptoms, the present study investigated the consequence of DBS at the IC on the catalepsy induced by haloperidol in rats. Additionally, we investigated if DBS of the IC can elicit motor responses in anesthetized rats and whether DBS elicits distinct neural firing patterns of activity at the dorsal cortex (DCIC) or central nucleus (CNIC) of the IC. A significant reduction of the catalepsy response was seen in rats previously given haloperidol and receiving DBS at the IC. In addition, electrical stimulation to the ventral part of the CNIC induced immediate motor responses in anesthetized rats. The neuronal spontaneous activity was higher at the ventral part of the CNIC than the dorsal part. DBS to the ventral part but not to the dorsal part of the CNIC increased the spike rate at neurons a few hundred microns away from the stimulation site. It is possible that the IC plays a role in the sensorimotor gating activated by emotional stimuli, and that DBS at the IC can be a promising new animal model to study paradoxical kinesia in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Mass Spectrometry Method to Measure Membrane Proteins in Dried Blood Spots for the Detection of Blood Doping Practices in Sport.

PubMed

Cox, Holly D; Eichner, Daniel

2017-09-19

The dried blood spot (DBS) matrix has significant utility for applications in the field where venous blood collection and timely shipment of labile blood samples is difficult. Unfortunately, protein measurement in DBS is hindered by high abundance proteins and matrix interference that increases with hematocrit. We developed a DBS method to enrich for membrane proteins and remove soluble proteins and matrix interference. Following a wash in a series of buffers, the membrane proteins are digested with trypsin and quantitated by parallel reaction monitoring mass spectrometry methods. The DBS method was applied to the quantification of four cell-specific cluster of differentiation (CD) proteins used to count cells by flow cytometry, band 3 (CD233), CD71, CD45, and CD41. We demonstrate that the DBS method counts low abundance cell types such as immature reticulocytes as well as high abundance cell types such as red blood cells, white blood cells, and platelets. When tested in 82 individuals, counts obtained by the DBS method demonstrated good agreement with flow cytometry and automated hematology analyzers. Importantly, the method allows longitudinal monitoring of CD protein concentration and calculation of interindividual variation which is difficult by other methods. Interindividual variation of band 3 and CD45 was low, 6 and 8%, respectively, while variation of CD41 and CD71 was higher, 18 and 78%, respectively. Longitudinal measurement of CD71 concentration in DBS over an 8-week period demonstrated intraindividual variation 17.1-38.7%. Thus, the method may allow stable longitudinal measurement of blood parameters currently monitored to detect blood doping practices.

Multiplexed Quantitation of Endogenous Proteins in Dried Blood Spots by Multiple Reaction Monitoring - Mass Spectrometry

PubMed Central

Chambers, Andrew G.; Percy, Andrew J.; Yang, Juncong; Camenzind, Alexander G.; Borchers, Christoph H.

2013-01-01

Dried blood spot (DBS) sampling, coupled with multiple reaction monitoring mass spectrometry (MRM-MS), is a well-established approach for quantifying a wide range of small molecule biomarkers and drugs. This sampling procedure is simpler and less-invasive than those required for traditional plasma or serum samples enabling collection by minimally trained personnel. Many analytes are stable in the DBS format without refrigeration, which reduces the cost and logistical challenges of sample collection in remote locations. These advantages make DBS sample collection desirable for advancing personalized medicine through population-wide biomarker screening. Here we expand this technology by demonstrating the first multiplexed method for the quantitation of endogenous proteins in DBS samples. A panel of 60 abundant proteins in human blood was targeted by monitoring proteotypic tryptic peptides and their stable isotope-labeled analogs by MRM. Linear calibration curves were obtained for 40 of the 65 peptide targets demonstrating multiple proteins can be quantitatively extracted from DBS collection cards. The method was also highly reproducible with a coefficient of variation of <15% for all 40 peptides. Overall, this assay quantified 37 proteins spanning a range of more than four orders of magnitude in concentration within a single 25 min LC/MRM-MS analysis. The protein abundances of the 33 proteins quantified in matching DBS and whole blood samples showed an excellent correlation, with a slope of 0.96 and an R2 value of 0.97. Furthermore, the measured concentrations for 80% of the proteins were stable for at least 10 days when stored at −20 °C, 4 °C and 37 °C. This work represents an important first step in evaluating the integration of DBS sampling with highly-multiplexed MRM for quantitation of endogenous proteins. PMID:23221968

Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever.

PubMed

Page-Sharp, Madhu; Coward, Jonathan; Moore, Brioni R; Salman, Sam; Marshall, Lewis; Davis, Timothy M E; Batty, Kevin T; Manning, Laurens

2017-08-01

Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and >1 month at -20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD. Copyright © 2017 American Society for Microbiology.

Lack of benefit of accumbens/capsular deep brain stimulation in a patient with both tics and obsessive-compulsive disorder.

PubMed

Burdick, Adam; Foote, Kelly D; Goodman, Wayne; Ward, Herbert E; Ricciuti, Nicola; Murphy, Tanya; Haq, Ihtsham; Okun, Michael S

2010-08-01

LAY SUMMARY: This case report illustrates lack of clinical efficacy of deep brain stimulation (DBS) for control of tics in a case of mild Tourette syndrome (TS) with severe comorbid obsessive-compulsive disorder (OCD). The brain target for stimulation was the anterior limb internal capsule (ALIC). To investigate the effect of anterior limb of internal capsule/nucleus accumbens (ALIC-NA) DBS on mild motor and vocal tics in a Tourette syndrome (TS) patient with severe OCD. The optimum target to address symptoms of TS with DBS remains unknown. Earlier lesional therapy utilized thalamic targets and also the ALIC for select cases which had been diagnosed with other psychiatric disorders. Evidence regarding the efficacy of DBS for the symptoms of TS may aid in better defining a brain target's suitability for use. We report efficacy data on ALIC-NA DBS in a patient with severe OCD and mild TS. A 33-year-old man underwent bilateral ALIC-NA DBS. One month following implantation, a post-operative CT scan was obtained to verify lead locations. Yale Global Tic Severity Scales (YGTSS) and modified Rush Videotape Rating scales (MRVRS) were obtained throughout the first 6 months, as well as careful clinical examinations by a specialized neurology and psychiatry team. The patient has been followed for 30 months. YGTSS scores worsened by 17% during the first 6 months. MRVRS scores also worsened over 30 total months of follow-up. There was a lack of clinically significant tic reduction although subjectively the patient felt tics improved mildly. DBS in the ALIC-NA failed to effectively address mild vocal and motor tics in a patient with TS and severe comorbid OCD.

Deep Brain Stimulation in Anorexia Nervosa: Hope for the Hopeless or Exploitation of the Vulnerable? The Oxford Neuroethics Gold Standard Framework

PubMed Central

Park, Rebecca J.; Singh, Ilina; Pike, Alexandra C.; Tan, Jacinta O. A.

2017-01-01

Neurosurgical interventions for psychiatric disorders have a long and troubled history (1, 2) but have become much more refined in the last few decades due to the rapid development of neuroimaging and robotic technologies (2). These advances have enabled the design of less invasive techniques, which are more focused, such as deep brain stimulation (DBS) (3). DBS involves electrode insertion into specific neural targets implicated in pathological behavior, which are then repeatedly stimulated at adjustable frequencies. DBS has been used for Parkinson’s disease and movement disorders since the 1960s (4–6) and over the last decade has been applied to treatment-refractory psychiatric disorders, with some evidence of benefit in obsessive–compulsive disorder (OCD), major depressive disorder, and addictions (7). Recent consensus guidelines on best practice in psychiatric neurosurgery (8) stress, however, that DBS for psychiatric disorders remains at an experimental and exploratory stage. The ethics of DBS—in particular for psychiatric conditions—is debated (1, 8–10). Much of this discourse surrounds the philosophical implications of competence, authenticity, personality, or identity change following neurosurgical interventions, but there is a paucity of applied guidance on neuroethical best practice in psychiatric DBS, and health-care professionals have expressed that they require more (11). This paper aims to redress this balance by providing a practical, applied neuroethical gold standard framework to guide research ethics committees, researchers, and institutional sponsors. We will describe this as applied to our protocol for a particular research trial of DBS in severe and enduring anorexia nervosa (SE-AN) (https://clinicaltrials.gov/ct2/show/NCT01924598, unique identifier NCT01924598), but believe it may have wider application to DBS in other psychiatric disorders. PMID:28373849

Quantitative determination of opioids in whole blood using fully automated dried blood spot desorption coupled to on-line SPE-LC-MS/MS.

PubMed

Verplaetse, Ruth; Henion, Jack

2016-01-01

Opioids are well known, widely used painkillers. Increased stability of opioids in the dried blood spot (DBS) matrix compared to blood/plasma has been described. Other benefits provided by DBS techniques include point-of-care collection, less invasive micro sampling, more economical shipment, and convenient storage. Current methodology for analysis of micro whole blood samples for opioids is limited to the classical DBS workflow, including tedious manual punching of the DBS cards followed by extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalysis. The goal of this study was to develop and validate a fully automated on-line sample preparation procedure for the analysis of DBS micro samples relevant to the detection of opioids in finger prick blood. To this end, automated flow-through elution of DBS cards was followed by on-line solid-phase extraction (SPE) and analysis by LC-MS/MS. Selective, sensitive, accurate, and reproducible quantitation of five representative opioids in human blood at sub-therapeutic, therapeutic, and toxic levels was achieved. The range of reliable response (R(2)  ≥0.997) was 1 to 500 ng/mL whole blood for morphine, codeine, oxycodone, hydrocodone; and 0.1 to 50 ng/mL for fentanyl. Inter-day, intra-day, and matrix inter-lot accuracy and precision was less than 15% (even at lower limits of quantitation (LLOQ) level). The method was successfully used to measure hydrocodone and its major metabolite norhydrocodone in incurred human samples. Our data support the enormous potential of DBS sampling and automated analysis for monitoring opioids as well as other pharmaceuticals in both anti-doping and pain management regimens. Copyright © 2015 John Wiley & Sons, Ltd.

Novel fingerprinting method characterises the necessary and sufficient structural connectivity from deep brain stimulation electrodes for a successful outcome

NASA Astrophysics Data System (ADS)

Fernandes, Henrique M.; Van Hartevelt, Tim J.; Boccard, Sandra G. J.; Owen, Sarah L. F.; Cabral, Joana; Deco, Gustavo; Green, Alex L.; Fitzgerald, James J.; Aziz, Tipu Z.; Kringelbach, Morten L.

2015-01-01

Deep brain stimulation (DBS) is a remarkably effective clinical tool, used primarily for movement disorders. DBS relies on precise targeting of specific brain regions to rebalance the oscillatory behaviour of whole-brain neural networks. Traditionally, DBS targeting has been based upon animal models (such as MPTP for Parkinson’s disease) but has also been the result of serendipity during human lesional neurosurgery. There are, however, no good animal models of psychiatric disorders such as depression and schizophrenia, and progress in this area has been slow. In this paper, we use advanced tractography combined with whole-brain anatomical parcellation to provide a rational foundation for identifying the connectivity ‘fingerprint’ of existing, successful DBS targets. This knowledge can then be used pre-surgically and even potentially for the discovery of novel targets. First, using data from our recent case series of cingulate DBS for patients with treatment-resistant chronic pain, we demonstrate how to identify the structural ‘fingerprints’ of existing successful and unsuccessful DBS targets in terms of their connectivity to other brain regions, as defined by the whole-brain anatomical parcellation. Second, we use a number of different strategies to identify the successful fingerprints of structural connectivity across four patients with successful outcomes compared with two patients with unsuccessful outcomes. This fingerprinting method can potentially be used pre-surgically to account for a patient’s individual connectivity and identify the best DBS target. Ultimately, our novel fingerprinting method could be combined with advanced whole-brain computational modelling of the spontaneous dynamics arising from the structural changes in disease, to provide new insights and potentially new targets for hitherto impenetrable neuropsychiatric disorders.

Neurotransmitter activity is linked to outcome following subthalamic deep brain stimulation in Parkinson's disease.

PubMed

O'Gorman Tuura, Ruth L; Baumann, Christian R; Baumann-Vogel, Heide

2018-05-01

While the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's Disease (PD) are not yet fully understood, DBS appears to exert a wide range of neurochemical effects on the network level, thought to arise from activation of inhibitory and excitatory pathways. The activity within the primary inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmitter systems may therefore play an important role in the therapeutic efficacy of DBS in PD. The purpose of this study was to investigate abnormalities in GABA-ergic and glutamatergic neurotransmission in PD, and to examine the link between neurotransmitter levels and outcome following DBS. Magnetic resonance spectra were acquired from the pons and basal ganglia in sixteen patients with PD and sixteen matched control participants. GABA and glutamate levels were quantified with LCModel, an automated spectral fitting package. Fourteen patients subsequently underwent DBS, and PD symptoms were evaluated with the MDS-UPDRS at baseline and six months after surgery. The efficacy of DBS treatment was evaluated from the percentage improvement in MDS-UPDRS scores. Basal ganglia GABA levels were significantly higher in PD patients relative to control participants (p < 0.01), while pontine glutamate + glutamine (Glx) levels were significantly lower in patients with PD (p < 0.05). While GABA levels were not significantly related to outcome post-surgery, basal ganglia glutamate levels emerged as a significant predictor of outcome, suggesting a possible role for glutamatergic neurotransmission in the therapeutic mechanism of DBS. GABAergic and glutamatergic neurotransmission is altered in PD, and glutamatergic activity in particular may influence outcome post-surgery. Copyright © 2018 Elsevier Ltd. All rights reserved.

The epistemology of Deep Brain Stimulation and neuronal pathophysiology

PubMed Central

Montgomery, Erwin B.

2012-01-01

Deep Brain Stimulation (DBS) is a remarkable therapy succeeding where all manner of pharmacological manipulations and brain transplants fail. The success of DBS has resurrected the relevance of electrophysiology and dynamics on the order of milliseconds. Despite the remarkable effects of DBS, its mechanisms of action are largely unknown. There has been an expanding catalogue of various neuronal and neural responses to DBS or DBS-like stimulation but no clear conceptual encompassing explanatory scheme has emerged despite the technological prowess and intellectual sophistication of the scientists involved. Something is amiss. If the scientific observations are sound, then why has there not been more progress? The alternative is that it may be the hypotheses that frame the questions are at fault as well as the methods of inference (logic) used to validate the hypotheses. An analysis of the past and current notions of the DBS mechanisms of action is the subject in order to identify the presuppositions (premises) and logical fallacies that may be at fault. The hope is that these problems will be avoided in the future so the DBS can realize its full potential quickly. In this regard, the discussion of the methods of inference and presuppositions that underlie many current notions is no different then a critique of experimental methods common in scientific discussions and consequently, examinations of the epistemology and logic are appropriate. This analysis is in keeping with the growing appreciation among scientists and philosophers of science, the scientific observations (data) to not “speak for themselves” nor is the scientific method self-evidently true and that consideration of the underlying inferential methods is necessary. PMID:23024631

Lubiprostone stimulates duodenal bicarbonate secretion in rats.

PubMed

Mizumori, Misa; Akiba, Yasutada; Kaunitz, Jonathan D

2009-10-01

Lubiprostone, a bicyclic fatty acid, is used for the treatment of chronic constipation. No published study has addressed the effect of lubiprostone on intestinal ion secretion in vivo. The aim of this study was to test the hypothesis that lubiprostone augments duodenal HCO(3) (-) secretion (DBS). Rat proximal duodenal loops were perfused with pH 7.0 Krebs, control vehicle (medium-chain triglycerides), or lubiprostone (0.1-10 microM). We measured DBS with flow-through pH and CO(2) electrodes, perfusate [Cl(-)] with a Cl(-) electrode, and water flux using a non-absorbable ferrocyanide marker. Some rats were pretreated with a potent, selective CFTR antagonist, CFTR(inh)-172 (1 mg/kg, ip), 1 h before experiments. Perfusion of lubiprostone concentration dependently increased DBS, whereas net Cl(-) output and net water output were only increased at 0.1 microM, compared with vehicle. CFTR(inh)-172 reduced lubiprostone (10 microM)-induced DBS increase, whereas net Cl(-) output was also unchanged. Nevertheless, CFTR(inh)-172 reduced basal net water output, which was reversed by lubiprostone. Furthermore, lubiprostone-induced DBS was inhibited by EP4 receptor antagonist, not by an EP1/2 receptor antagonist or by indomethacin pretreatment. In this first study of the effect of lubiprostone on intestinal ion secretion in vivo, lubiprostone stimulated CFTR-dependent DBS without changing net Cl(-) secretion. This effect supports the hypothesis that Cl(-) secreted by CFTR is recycled across the apical membrane by anion exchangers. Recovery of water output during CFTR inhibition suggests that lubiprostone may improve the intestinal phenotype in CF patients. Furthermore, increased DBS suggests that lubiprostone may protect the duodenum from acid-induced injury via EP4 receptor activation.

Effects of Subthalamic Stimulation on Olfactory Function in Parkinson Disease.

PubMed

Cury, Rubens Gisbert; Carvalho, Margarete de Jesus; Lasteros, Fernando Jeyson Lopez; Dias, Alice Estevo; Dos Santos Ghilardi, Maria Gabriela; Paiva, Anderson Rodrigues Brandão; Coutinho, Artur Martins; Buchpiguel, Carlos Alberto; Teixeira, Manoel J; Barbosa, Egberto Reis; Fonoff, Erich Talamoni

2018-06-01

Olfactory dysfunction is a nonmotor symptom of Parkinson disease (PD) associated with reduction in quality of life. There is no evidence on whether improvements in olfaction after subthalamic deep brain stimulation (STN-DBS) may be directly attributable to motor improvement or whether this reflects a direct effect of DBS on olfactory brain areas. The aim of the present study was to evaluate the effect of DBS on olfactory function in PD, as well as to explore the correlation between these changes and changes in motor symptoms and brain metabolism. Thirty-two patients with PD were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. Primary outcome was the change in olfactory function (Sniffin' Sticks odor-identification test [SST]) after surgery among the patients with hyposmia at baseline. Secondary outcomes included the relationship between motor outcomes and olfactory changes and [ 18 F]fluorodeoxyglucose-positron emission tomography analysis between subgroups with improvement versus no improvement of smell. STN-DBS improved SST after surgery (preoperative SST, median 7.3 ± 2.4 vs. postoperative SST, median 8.2 ± 2.1; P = 0.045) in a subset of patients among 29 of 32 patients who presented with hyposmia at baseline. The improvement in SST was correlated with DBS response (r = 0.424; P = 0.035). There was also an increase in glucose metabolism in the midbrain, cerebellum, and right frontal lobe in patients with SST improvement (P < 0.001). STN-DBS improves odor identification in a subset of patients with PD. Motor improvement together with changes in the brain metabolism may be linked to this improvement. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuropsychological function before and after subcallosal cingulate deep brain stimulation in patients with treatment-resistant depression.

PubMed

Moreines, Jared L; McClintock, Shawn M; Kelley, Mary E; Holtzheimer, Paul E; Mayberg, Helen S

2014-08-01

Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD. Patients with TRD (N = 17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm. Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable. Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function. © 2014 Wiley Periodicals, Inc.

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease.

PubMed

Maruo, Tomoyuki; Saitoh, Youichi; Hosomi, Koichi; Kishima, Haruhiko; Shimokawa, Toshio; Hirata, Masayuki; Goto, Tetsu; Morris, Shayne; Harada, Yu; Yanagisawa, Takufumi; Aly, Mohamed M; Yoshimine, Toshiki

2011-04-01

Patients with Parkinson's disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P<.001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P<.02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P<.02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

NEUROPSYCHOLOGICAL FUNCTION BEFORE AND AFTER SUBCALLOSAL CINGULATE DEEP BRAIN STIMULATION IN PATIENTS WITH TREATMENT-RESISTANT DEPRESSION

PubMed Central

Moreines, Jared L.; McClintock, Shawn M.; Kelley, Mary E.; Holtzheimer, Paul E.; Mayberg, Helen S.

2014-01-01

Background Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD. Methods Patients with TRD (N =17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm. Results Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable. Conclusions Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function. PMID:24753183

Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial.

PubMed

Wharen, Robert E; Okun, Michael S; Guthrie, Barton L; Uitti, Ryan J; Larson, Paul; Foote, Kelly; Walker, Harrison; Marshall, Frederick J; Schwalb, Jason; Ford, Blair; Jankovic, Joseph; Simpson, Richard; Dashtipour, Khashayar; Phibbs, Fenna; Neimat, Joseph S; Stewart, R Malcolm; Peichel, DeLea; Pahwa, Rajesh; Ostrem, Jill L

2017-07-01

This study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET). A prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications. The primary outcome measure was a rater-blinded assessment of the change in the target limb tremor score in the stimulation-on versus stimulation-off state six months following surgery. Multiple secondary outcomes were assessed at one-year follow-up, including motor, mood, and quality-of-life measures. 127 patients were implanted with VIM DBS. The blinded, primary outcome variable (n = 76) revealed a mean improvement of 1.25 ± 1.26 points in the target limb tremor rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary outcome variables at one year revealed significant improvements (p ≤ 0.001) in quality of life, depression symptoms, and ADL scores. Forty-seven patients had a second contralateral VIM-DBS, and this group demonstrated reduction in second-sided tremor at 180 days (p < 0.001). Serious adverse events related to the surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device explantation (n = 3). Unilateral and bilateral constant-current VIM DBS significantly improves upper extremity tremor, ADL, quality of life, and depression in patients with severe ET. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quantification of Rifapentine, a Potent Antituberculosis Drug, from Dried Blood Spot Samples Using Liquid Chromatographic-Tandem Mass Spectrometric Analysis

PubMed Central

Parsons, Teresa L.; Marzinke, Mark A.; Hoang, Thuy; Bliven-Sizemore, Erin; Weiner, Marc; Mac Kenzie, William R.; Dorman, Susan E.

2014-01-01

The quantification of antituberculosis drug concentrations in multinational trials currently requires the collection of modest blood volumes, centrifugation, aliquoting of plasma, freezing, and keeping samples frozen during shipping. We prospectively enrolled healthy individuals into the Tuberculosis Trials Consortium Study 29B, a phase I dose escalation study of rifapentine, a rifamycin under evaluation in tuberculosis treatment trials. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying rifapentine in whole blood on dried blood spots (DBS) to facilitate pharmacokinetic/pharmacodynamic analyses in clinical trials. Paired plasma and whole-blood samples were collected by venipuncture, and whole blood was spotted on Whatman protein saver 903 cards. The methods were optimized for plasma and then validated for DBS. The analytical measuring range for quantification of rifapentine and its metabolite was 50 to 80,000 ng/ml in whole-blood DBS. The analyte was stable on the cards for 11 weeks with a desiccant at room temperature and protected from light. The method concordance for paired plasma and whole-blood DBS samples was determined after correcting for participant hematocrit or population-based estimates of bias from Bland-Altman plots. The application of either correction factor resulted in acceptable correlation between plasma and whole-blood DBS (Passing-Bablok regression corrected for hematocrit; y = 0.98x + 356). Concentrations of rifapentine may be determined from whole-blood DBS collected via venipuncture after normalization in order to account for the dilutional effects of red blood cells. Additional studies are focused on the application of this methodology to capillary blood collected by finger stick. The simplicity of processing, storage, shipping, and low blood volume makes whole-blood DBS attractive for rifapentine pharmacokinetic evaluations, especially in international and pediatric trials. PMID:25182637

Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice

PubMed Central

Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J.; Curry, Daniel J.; Samaco, Rodney C.; Zoghbi, Huda Y.; Tang, Jianrong

2016-01-01

Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnestic rats have demonstrated that DBS targeted to the fimbria-fornix1-3, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory3-5. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder (IDD). IDDs are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We hypothesized that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett Syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP26, RTT appears by the second year of life, causing profound impairment in cognitive, motor, and social skills along with an array of neurological features7; RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity8-11. Here we show that forniceal DBS in RTT mice rescued contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restored in vivo hippocampal long-term potentiation (LTP) and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053

Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus.

PubMed

Lentz, Linnea; Zhao, Yan; Kelly, Matthew T; Schindeldecker, William; Goetz, Steven; Nelson, Dwight E; Raike, Robert S

2015-11-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia. Copyright © 2015 Elsevier Inc. All rights reserved.

[Early Experience with the Vercise^TM DBS System in the Treatment of Dystonic Tremor].

PubMed

Miyagi, Yasushi

2017-03-01

Six cases of dystonic tremor were treated with the Vercise^TM deep brain stimulation(DBS)system, which has the multiple independent current control(MICC)technology. The mean preoperative score of Burke-Fahn-Marsden dystonia rating scale was 16.2±9.4, which was reduced to 6.1±4.6 at 5 months postoperatively. A 65-year-old male presented an intractable dystonic tremor of the jaw, neck, and shoulders due to tardive syndrome. He experienced the successful tremor relief after unipolar DBS in the globus pallidus internus(GPi)with Vercise^TM but complained of dysarthria. Steering the current ventrally induced nausea without alleviating dysarthria, while steering the current dorsally alleviated dysarthria but a further dorsal current induced mandibular dyskinesia. The current steering with MICC enabled the simulation field in GPi with successful balance, maximizing tremor suppression, and minimizing the adverse effects. In a second case, 61-year-old male in whom cervical dystonia with rotatory tremor had been successfully treated with interleaving stimulation of GPi-DBS had needed to repeat the replacement of a non-rechargeable pulse generator in only 15-month interval. After the substitution of Vercise^TM, the interleaving stimulation of 9.5mA in total was replaced by 8.5mA with the current steering of MICC, while the patient's symptomatic control was unchanged. The microlesion effects after lead implantation are unclear and therapeutic effects are often delayed in cases of dystonia;therefore, the submaximal stimulation intensities must be frequently applied in the early phase following the implantation of DBS. A fine current steering of Vercise^TM DBS is very useful in both, the early and late phases of GPi-DBS for dystonic syndrome.

Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior.

PubMed

Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Ami-Ad, Lavi; Yaka, Rami; Yadid, Gal

2010-11-01

The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25-1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5-20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABA(A)β, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA. Copyright © 2010 Elsevier Ltd. All rights reserved.

Penicillin Dried Blood Spot Assay for Use in Patients Receiving Intramuscular Benzathine Penicillin G and Other Penicillin Preparations To Prevent Rheumatic Fever

PubMed Central

Page-Sharp, Madhu; Coward, Jonathan; Moore, Brioni R.; Marshall, Lewis; Batty, Kevin T.

2017-01-01

ABSTRACT Rheumatic heart disease (RHD) remains an important global health challenge. Administration of benzathine penicillin (BPG) every 3 to 4 weeks is recommended as a secondary prophylaxis to prevent recurrent episodes of acute rheumatic fever and subsequent RHD. Following intramuscular injection, BPG is hydrolyzed to penicillin G (benzylpenicillin). However, little is known of the pharmacokinetics (PK) of BPG in pediatric populations at high risk of RHD or of the pharmacokinetic-pharmacodynamic relationship between penicillin exposure and clinically relevant outcomes. Dried blood spot (DBS) assays can facilitate PK studies in situations where frequent venous blood sampling is logistically difficult. A liquid chromatography-mass spectroscopy assay for penicillin G in plasma and DBS was developed and validated. Application of the DBS assay for PK studies was confirmed using samples from adult patients receiving penicillin as part of an infection management plan. The limit of quantification for penicillin G in DBS was 0.005 mg/liter. Penicillin G is stable in DBS for approximately 12 h at room temperature (22°C), 6 days at 4°C, and >1 month at −20°C. Plasma and DBS penicillin G concentrations for patients receiving BPG and penicillin G given via bolus doses correlated well and had comparable time-concentration profiles. There was poor correlation for patients receiving penicillin via continuous infusions, perhaps as a result of the presence of residual penicillin in the peripherally inserted central catheter, from which the plasma samples were collected. The present DBS penicillin G assay can be used as a surrogate for plasma concentrations to provide valid PK data for studies of BPG and other penicillin preparations developed to prevent rheumatic fever and RHD. PMID:28559267

Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior

PubMed Central

Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Ami-Ad, Lavi; Yaka, Rami; Yadid, Gal

2010-01-01

The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25–1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5–20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABAAβ, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA. PMID:20600170

Analysis of benzodiazepines and their metabolites using DBS cards and LC-MS/MS.

PubMed

Lee, Heesang; Park, Yujin; Jo, Jiyeong; In, Sangwhan; Park, Yonghoon; Kim, Eunmi; Pyo, Jaesung; Choe, Sanggil

2015-10-01

Dried Blood Spot (DBS) has been used a blood extraction method for inherited metabolic disorder screening since 1960s. With introduction of LC-MS/MS, not only DBS could be used to analysis drugs in small blood volume, but in various fields, such as toxicology, drug therapeutic monitoring, drug diagnostic screening, and illicit drugs. In toxicology field, many drugs (e.g. benzodiazepines, acetaminophen, small molecule drugs) have been tested with DBS. Compared with earlier blood extraction methods (SPE and LLE), DBS has lots of advantages; lower blood volume (less than 50μL), shorter analysis time caused by a more concise analysis procedure and lower cost. We optimized the DBS procedure and LC-MS/MS conditions for 18 benzodiazepines, seven benzodiazepine metabolites, and one z-drug (zolpidem) analysis in blood. 30μL of whole blood was spotted on FTA DMPK card C and dried for 2h in a desiccator. A 6-mm disk was punched and vortexed for 1min in a centrifuge tube with 300μL methanol/acetonitrile mixture (1:1, v/v). After evaporation, redissolved in 100μL mobile phase of LC-MS/MS and 5μL was injected. In the analysis for 26 target compounds in blood, all of the method validation parameters - LLOD, LLOQ, accuracy (intra- and inter-assay), and precision (intra- and inter-assay) - were satisfied with method validation criteria, within 15%. The results of matrix effect, recovery, and process efficiency were good. We developed a fast and reliable sample preparation method using DBS for 26 benzodiazepines, benzodiazepine metabolites, and z-drug (zolpidem). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of Hemoglobin A1c from Dried Blood Spot Samples with the Tina-quant® II Immunoturbidimetric Method

PubMed Central

Jones, Trevor G.; Warber, Kimbrough D.; Roberts, Billy D.

2010-01-01

Background Hemoglobin A1c (HbA1c) has been endorsed as a tool for the diagnosis of diabetes. This test requires instrumentation that may not be available in underdeveloped areas. Dried blood spot (DBS) samples collected by finger stick procedures offer a mechanism to transport samples to laboratories that do measure HbA1c. Methods Whole blood (ethylenediaminetetraacetic acid) was applied to Ahlstrom 226 filter paper. These DBS samples were compared to whole blood samples using the Roche Tina-quant® II immunoturbidometric assay. Hemoglobin A1c stability on DBS was assessed at three temperatures—4, 25, and 40°C—for up to 9 days. A 44-day study was also done for DBS at 20–25°C. Results The Tina-quant® II DBS method showed excellent agreement with whole blood HbA1c results (r2 = 0.99) with a slight positive mean bias of 0.08 ± 0.04% HbA1c (95% confidence interval). The variation in HbA1c on DBS samples subjected to different temperatures and times did not exceed 5.6%. Conclusions Dried blood spot samples represent an alternative to whole blood for HbA1c by measurement when transporting whole blood is not feasible. PMID:20307383

Deep Brain Stimulation for Early Stage Parkinson's Disease: An Illustrative Case

PubMed Central

Gill, Chandler E.; Allen, Laura A.; Konrad, Peter E.; Davis, Thomas L.; Bliton, Mark J.; Finder, Stuart G.; Tramontana, Michael G.; Kao, C. Chris; Remple, Michael S.; Bradenham, Courtney H.; Charles, P. David

2011-01-01

Objectives Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective intervention in advanced Parkinson's Disease (PD), but its efficacy and safety in early PD are unknown. Our team is conducting a randomized pilot trial investigating DBS in early PD. This report describes one participant who received bilateral STN-DBS. Materials/Methods Thirty subjects have been randomized to either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from the STN and substantia nigra (SN) are collected at implantation. The Unified Parkinson's Disease Rating Scale Motor Subscale (UPDRS-III) is administered in the ON and OFF states semi-annually and neuropsychological function and quality of life are assessed annually. We describe a 54-year-old man with a two-year history of PD who was randomized to DBS + ODT and followed for two years. Results The subject showed a lower STN to SN ratio of neuronal activity than advanced PD patients, and higher firing rate than non-PD patients. The subject's ON total UPDRS and UPDRS-III scores improved during the two-year follow-up, while his OFF UPDRS-III score and levodopa equivalent daily dose (LEDD) increased. Quality of life, verbal fluency and verbal learning improved. He did not experience any serious adverse events. Conclusions This report details the first successful application of bilateral STN DBS for early stage PD during a clinical trial. PMID:21939467

2D Doppler backscattering using synthetic aperture microwave imaging of MAST edge plasmas

NASA Astrophysics Data System (ADS)

Thomas, D. A.; Brunner, K. J.; Freethy, S. J.; Huang, B. K.; Shevchenko, V. F.; Vann, R. G. L.

2016-02-01

Doppler backscattering (DBS) is already established as a powerful diagnostic; its extension to 2D enables imaging of turbulence characteristics from an extended region of the cut-off surface. The Synthetic Aperture Microwave Imaging (SAMI) diagnostic has conducted proof-of-principle 2D DBS experiments of MAST edge plasma. SAMI actively probes the plasma edge using a wide (±40° vertical and horizontal) and tuneable (10-34.5 GHz) beam. The Doppler backscattered signal is digitised in vector form using an array of eight Vivaldi PCB antennas. This allows the receiving array to be focused in any direction within the field of view simultaneously to an angular range of 6-24° FWHM at 10-34.5 GHz. This capability is unique to SAMI and is a novel way of conducting DBS experiments. In this paper the feasibility of conducting 2D DBS experiments is explored. Initial observations of phenomena previously measured by conventional DBS experiments are presented; such as momentum injection from neutral beams and an abrupt change in power and turbulence velocity coinciding with the onset of H-mode. In addition, being able to carry out 2D DBS imaging allows a measurement of magnetic pitch angle to be made; preliminary results are presented. Capabilities gained through steering a beam using a phased array and the limitations of this technique are discussed.

Subthalamic deep brain stimulation in Parkinson׳s disease has no significant effect on perceptual timing in the hundreds of milliseconds range

PubMed Central

Cope, Thomas E.; Grube, Manon; Mandal, Arnab; Cooper, Freya E.; Brechany, Una; Burn, David J.; Griffiths, Timothy D.

2014-01-01

Bilateral, high-frequency stimulation of the basal ganglia (STN-DBS) is in widespread use for the treatment of the motor symptoms of Parkinson׳s disease (PD). We present here the first psychophysical investigation of the effect of STN-DBS upon perceptual timing in the hundreds of milliseconds range, with both duration-based (absolute) and beat-based (relative) tasks; 13 patients with PD were assessed with their STN-DBS ‘on’, ‘off’, and then ‘on’ again. Paired parametric analyses revealed no statistically significant differences for any task according to DBS status. We demonstrate, from the examination of confidence intervals, that any functionally relevant effect of STN-DBS on relative perceptual timing is statistically unlikely. For absolute, duration-based timing, we demonstrate that the activation of STN-DBS may either worsen performance or have no effect, but that it is unlikely to lead to significant improvement. Although these results are negative they have important implications for our understanding of perceptual timing and its relationship to motor functions within the timing network of the brain. They imply that the mechanisms involved in the perceptual processing of temporal information are likely to be functionally independent from those that underpin movement. Further, they suggest that the connections between STN and the subtantia nigra and globus pallidus are unlikely to be critical to beat-based perceptual timing. PMID:24613477

Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture.

PubMed

Elwassif, Maged M; Datta, Abhishek; Rahman, Asif; Bikson, Marom

2012-08-01

There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

Deep brain stimulation: a return journey from psychiatry to neurology.

PubMed

Ashkan, Keyoumars; Shotbolt, Paul; David, Anthony S; Samuel, Michael

2013-06-01

Deep brain stimulation (DBS) has emerged as an effective neurosurgical tool to treat a range of conditions. Its use in movement disorders such as Parkinson's disease, tremor and dystonia is now well established and has been approved by the National Institute of Clinical Excellence (NICE). The NICE does, however, emphasise the need for a multidisciplinary team to manage these patients. Such a team is traditionally composed of neurologists, neurosurgeons and neuropsychologists. Neuropsychiatrists, however, are increasingly recognised as essential members given many psychiatric considerations that may arise in patients undergoing DBS. Patient selection, assessment of competence to consent and treatment of postoperative psychiatric disease are just a few areas where neuropsychiatric input is invaluable. Partly driven by this close team working and partly based on the early history of DBS for psychiatric disorders, there is increasing interest in re-exploring the potential of neurosurgery to treat patients with psychiatric disease, such as depression and obsessive-compulsive disorder. Although the clinical experience and evidence with DBS in this group of patients are steadily increasing, many questions remain unanswered. Yet, the characteristics of optimal surgical candidates, the best choice of DBS target, the most effective stimulating parameters and the extent of postoperative improvement are not clear for most psychiatric conditions. Further research is therefore required to define how DBS can be best utilised to improve the quality of life of patients with psychiatric disease.

Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

PubMed

Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg; Sunde, Niels Aagaard; Johansen, Lars Gottfried; Beniczky, Sándor; Østergaard, Karen

2017-07-01

Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. The differentiated effect suggests differences in the effect mechanisms of the two treatments. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Hemispheric dissociation of reward processing in humans: insights from deep brain stimulation.

PubMed

Palminteri, Stefano; Serra, Giulia; Buot, Anne; Schmidt, Liane; Welter, Marie-Laure; Pessiglione, Mathias

2013-01-01

Rewards have various effects on human behavior and multiple representations in the human brain. Behaviorally, rewards notably enhance response vigor in incentive motivation paradigms and bias subsequent choices in instrumental learning paradigms. Neurally, rewards affect activity in different fronto-striatal regions attached to different motor effectors, for instance in left and right hemispheres for the two hands. Here we address the question of whether manipulating reward-related brain activity has local or general effects, with respect to behavioral paradigms and motor effectors. Neuronal activity was manipulated in a single hemisphere using unilateral deep brain stimulation (DBS) in patients with Parkinson's disease. Results suggest that DBS amplifies the representation of reward magnitude within the targeted hemisphere, so as to affect the behavior of the contralateral hand specifically. These unilateral DBS effects on behavior include both boosting incentive motivation and biasing instrumental choices. Furthermore, using computational modeling we show that DBS effects on incentive motivation can predict DBS effects on instrumental learning (or vice versa). Thus, we demonstrate the feasibility of causally manipulating reward-related neuronal activity in humans, in a manner that is specific to a class of motor effectors but that generalizes to different computational processes. As these findings proved independent from therapeutic effects on parkinsonian motor symptoms, they might provide insight into DBS impact on non-motor disorders, such as apathy or hypomania. Copyright © 2013 Elsevier Ltd. All rights reserved.

Wide-bore 1.5 T MRI-guided deep brain stimulation surgery: initial experience and technique comparison.

PubMed

Sillay, Karl A; Rusy, Deborah; Buyan-Dent, Laura; Ninman, Nancy L; Vigen, Karl K

2014-12-01

We report results of the initial experience with magnetic resonance image (MRI)-guided implantation of subthalamic nucleus (STN) deep brain stimulating (DBS) electrodes at the University of Wisconsin after having employed frame-based stereotaxy with previously available MR imaging techniques and microelectrode recording for STN DBS surgeries. Ten patients underwent MRI-guided DBS implantation of 20 electrodes between April 2011 and March 2013. The procedure was performed in a purpose-built intraoperative MRI suite configured specifically to allow MRI-guided DBS, using a wide-bore (70 cm) MRI system. Trajectory guidance was accomplished with commercially available system consisting of an MR-visible skull-mounted aiming device and a software guidance system processing intraoperatively acquired iterative MRI scans. A total of 10 patients (5 male, 5 female)-representative of the Parkinson Disease (PD) population-were operated on with standard technique and underwent 20 electrode placements under MRI-guided bilateral STN-targeted DBS placement. All patients completed the procedure with electrodes successfully placed in the STN. Procedure time improved with experience. Our initial experience confirms the safety of MRI-guided DBS, setting the stage for future investigations combining physiology and MRI guidance. Further follow-up is required to compare the efficacy of the MRI-guided surgery cohort to that of traditional frame-based stereotaxy. Copyright © 2014 Elsevier B.V. All rights reserved.

Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships.

PubMed

Geevarghese, Ruben; Lumsden, Daniel E; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

2016-01-01

Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.

Bimanual Force Coordination in Parkinson’s Disease Patients with Bilateral Subthalamic Deep Brain Stimulation

PubMed Central

Gorniak, Stacey L.; McIntyre, Cameron C.; Alberts, Jay L.

2013-01-01

Objective Studies of bimanual actions similar to activities of daily living (ADLs) are currently lacking in evaluating fine motor control in Parkinson’s disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS) patients. Methods Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition. Results The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition. Conclusion While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination. PMID:24244388

Deep Brain Stimulation Frequency—A Divining Rod for New and Novel Concepts of Nervous System Function and Therapy

PubMed Central

Montgomery, Erwin B.; He, Huang

2016-01-01

The efficacy of Deep Brain Stimulation (DBS) for an expanding array of neurological and psychiatric disorders demonstrates directly that DBS affects the basic electroneurophysiological mechanisms of the brain. The increasing array of active electrode configurations, stimulation currents, pulse widths, frequencies, and pulse patterns provides valuable tools to probe electroneurophysiological mechanisms. The extension of basic electroneurophysiological and anatomical concepts using sophisticated computational modeling and simulation has provided relatively straightforward explanations of all the DBS parameters except frequency. This article summarizes current thought about frequency and relevant observations. Current methodological and conceptual errors are critically examined in the hope that future work will not replicate these errors. One possible alternative theory is presented to provide a contrast to many current theories. DBS, conceptually, is a noisy discrete oscillator interacting with the basal ganglia–thalamic–cortical system of multiple re-entrant, discrete oscillators. Implications for positive and negative resonance, stochastic resonance and coherence, noisy synchronization, and holographic memory (related to movement generation) are presented. The time course of DBS neuronal responses demonstrates evolution of the DBS response consistent with the dynamics of re-entrant mechanisms. Finally, computational modeling demonstrates identical dynamics as seen by neuronal activities recorded from human and nonhuman primates, illustrating the differences of discrete from continuous harmonic oscillators and the power of conceptualizing the nervous system as composed on interacting discrete nonlinear oscillators. PMID:27548234

Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Datta, Abhishek; Rahman, Asif; Bikson, Marom

2012-08-01

There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

Simulation of cortico-basal ganglia oscillations and their suppression by closed loop deep brain stimulation.

PubMed

Grant, Peadar F; Lowery, Madeleine M

2013-07-01

A new model of deep brain stimulation (DBS) is presented that integrates volume conduction effects with a neural model of pathological beta-band oscillations in the cortico-basal ganglia network. The model is used to test the clinical hypothesis that closed-loop control of the amplitude of DBS may be possible, based on the average rectified value of beta-band oscillations in the local field potential. Simulation of closed-loop high-frequency DBS was shown to yield energy savings, with the magnitude of the energy saved dependent on the strength of coupling between the subthalamic nucleus and the remainder of the cortico-basal ganglia network. When closed-loop DBS was applied to a strongly coupled cortico-basal ganglia network, the stimulation energy delivered over a 480 s period was reduced by up to 42%. Greater energy reductions were observed for weakly coupled networks, as the stimulation amplitude reduced to zero once the initial desynchronization had occurred. The results provide support for the application of closed-loop high-frequency DBS based on electrophysiological biomarkers.

Acoustic Analysis of PD Speech

PubMed Central

Chenausky, Karen; MacAuslan, Joel; Goldhor, Richard

2011-01-01

According to the U.S. National Institutes of Health, approximately 500,000 Americans have Parkinson's disease (PD), with roughly another 50,000 receiving new diagnoses each year. 70%–90% of these people also have the hypokinetic dysarthria associated with PD. Deep brain stimulation (DBS) substantially relieves motor symptoms in advanced-stage patients for whom medication produces disabling dyskinesias. This study investigated speech changes as a result of DBS settings chosen to maximize motor performance. The speech of 10 PD patients and 12 normal controls was analyzed for syllable rate and variability, syllable length patterning, vowel fraction, voice-onset time variability, and spirantization. These were normalized by the controls' standard deviation to represent distance from normal and combined into a composite measure. Results show that DBS settings relieving motor symptoms can improve speech, making it up to three standard deviations closer to normal. However, the clinically motivated settings evaluated here show greater capacity to impair, rather than improve, speech. A feedback device developed from these findings could be useful to clinicians adjusting DBS parameters, as a means for ensuring they do not unwittingly choose DBS settings which impair patients' communication. PMID:21977333

Some Clinically Useful Information that Neuropsychology Provides Patients, Carepartners, Neurologists, and Neurosurgeons About Deep Brain Stimulation for Parkinson's Disease

PubMed Central

Tröster, Alexander I

2017-01-01

Abstract Deep brain stimulation (DBS) is an effective (but non-curative) treatment for some of the motor symptoms and treatment complications associated with dopaminergic agents in Parkinson's disease (PD). DBS can be done relatively safely and is associated with quality of life gains. In most DBS centers, neuropsychological evaluations are performed routinely before surgery, and sometimes after surgery. The purpose of such evaluation is not to decide solely on its results whether or not to offer DBS to a given candidate, but to provide the patient and treatment team with the best available information to make reasonable risk-benefit assessments. This review provides information relevant to the questions often asked by patients and their carepartners, neurologists, and neurosurgeons about neuropsychological outcomes of DBS, including neuropsychological adverse event rates, magnitude of cognitive changes, outcomes after unilateral versus bilateral surgery directed at various targets, impact of mild cognitive impairment (MCI) on outcome, factors implicated in neurobehavioral outcomes, and safety of newer interventions or techniques such as asleep surgery and current steering. PMID:29077802

Assessment of the within- and between-lot variability of Whatman™ FTA(®) DMPK and 903(®) DBS papers and their suitability for the quantitative bioanalysis of small molecules.

PubMed

Luckwell, Jacquelynn; Denniff, Philip; Capper, Stephen; Michael, Paul; Spooner, Neil; Mallender, Philip; Johnson, Barry; Clegg, Sarah; Green, Mark; Ahmad, Sheelan; Woodford, Lynsey

2013-11-01

To ensure that PK data generated from DBS samples are of the highest quality, it is important that the paper substrate is uniform and does not unduly contribute to variability. This study investigated any within and between lot variations for four cellulose paper types: Whatman™ FTA(®) DMPK-A, -B and -C, and 903(®) (GE Healthcare, Buckinghamshire, UK). The substrates were tested to demonstrate manufacturing reproducibility (thickness, weight, chemical coating concentration) and its effect on the size of the DBS produced, and the quantitative data derived from the bioanalysis of human DBS samples containing six compounds of varying physicochemical properties. Within and between lot variations in paper thickness, mass and chemical coating concentration were within acceptable manufacturing limits. No variation in the spot size or bioanalytical data was observed. Bioanalytical results obtained for DBS samples containing a number of analytes spanning a range of chemical space are not affected by the lot used or by the location within a lot.

Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease.

PubMed

Hickey, Patrick; Stacy, Mark

2016-01-01

Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management.

Parkinson's Disease

MedlinePlus

... of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work ... of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work ...

Thalamic Deep Brain Stimulation for Writer's Cramp.

PubMed

Cho, Chul Bum; Park, Hae Kwan; Lee, Kyung Jin; Rha, Hyoung Kyun

2009-07-01

Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. There has been renewed interest in neurosurgical procedures for the treatment of dystonia over the past several years. In particular, deep brain stimulation (DBS) has received increasing attention as a therapeutic option for patients with dystonia. However, to date, limited reporters made investigations into DBS in relation to the Writer's cramp. In this case, unilateral Ventro-oralis complex (Vo) DBS resulted in a major improvement in patient's focal dystonic movement disorders. Her post-operative Burke-Fahn-Marsden Dystonia Rating (BFMDR) scale demonstrated 1 compared with pre-operative BFMDR scale 4. We conclude that thalamic Vo complex DBS may be an important neurosurgical therapeutic option for Writer's cramp.

[The role of neurologists in deep brain stimulation for Parkinson disease: a neurosurgical perspective].

PubMed

Umemura, Atsushi

2012-01-01

Deep brain stimulation (DBS) has been accepted as an effective treatment for medically refractory Parkinson disease (PD). Appropriate patient selection, safe and precise surgery, and proper postoperative adjustment of stimulation and medication, are essential for the success of DBS. Patient selection is the most important role for the neurologist in DBS treatment. Neurologists treating PD should understand the correct indications and contraindications for DBS, and introduce it in a timely manner to patients who can be expected to benefit substantially from it. For long term treatment of PD, ideally the neurologist in charge of the patient should adjust both the stimulation parameters and medication. Neurologists engaged in this treatment should also have a comprehensive understanding of the probable complications and how to avoid them.

Stuttering in Parkinson's disease after deep brain stimulation: A note on dystonia and low-frequency stimulation.

PubMed

Mendonça, Marcelo D; Barbosa, Raquel; Seromenho-Santos, Alexandra; Reizinho, Carla; Bugalho, Paulo

2018-04-01

Stuttering, a speech fluency disorder, is a rare complication of Deep Brain Stimulation (DBS) in Parkinson's Disease (PD). We report a 61 years-old patient with PD, afflicted by severe On and Off dystonia, treated with Subthalamic Nucleus DBS that developed post-DBS stuttering while on 130 Hz stimulation. Stuttering reduction was noted when frequency was changed to 80 Hz, but the previously observed dystonia improvement was lost. There are no reports in literature on patients developing stuttering with low-frequency stimulation. We question if low-frequency stimulation could have a role for managing PD's post-DBS stuttering, and notice that stuttering improvement was associated with dystonia worsening suggesting that they are distinct phenomena. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pathway Tools version 13.0: integrated software for pathway/genome informatics and systems biology

PubMed Central

Paley, Suzanne M.; Krummenacker, Markus; Latendresse, Mario; Dale, Joseph M.; Lee, Thomas J.; Kaipa, Pallavi; Gilham, Fred; Spaulding, Aaron; Popescu, Liviu; Altman, Tomer; Paulsen, Ian; Keseler, Ingrid M.; Caspi, Ron

2010-01-01

Pathway Tools is a production-quality software environment for creating a type of model-organism database called a Pathway/Genome Database (PGDB). A PGDB such as EcoCyc integrates the evolving understanding of the genes, proteins, metabolic network and regulatory network of an organism. This article provides an overview of Pathway Tools capabilities. The software performs multiple computational inferences including prediction of metabolic pathways, prediction of metabolic pathway hole fillers and prediction of operons. It enables interactive editing of PGDBs by DB curators. It supports web publishing of PGDBs, and provides a large number of query and visualization tools. The software also supports comparative analyses of PGDBs, and provides several systems biology analyses of PGDBs including reachability analysis of metabolic networks, and interactive tracing of metabolites through a metabolic network. More than 800 PGDBs have been created using Pathway Tools by scientists around the world, many of which are curated DBs for important model organisms. Those PGDBs can be exchanged using a peer-to-peer DB sharing system called the PGDB Registry. PMID:19955237

Evaluation of a novel dried blood spot collection device (HemaSpot™) to test blood samples collected from dogs for antibodies to Leishmania infantum.

PubMed

Rosypal, Alexa C; Pick, Leanne D; Hernandez, Jaime O Esquivel; Lindsay, David S

2014-09-15

Collection of blood samples from veterinary and wildlife patients is often challenging because the samples have to be collected on farm or in the wild under various environmental conditions. This poses many technical problems associated with venipuncture materials, their safe use and disposal, transportation and processing of collected samples. Dried blood spot (DBS) sample collection techniques offer a simple and practical alternative to traditional blood collection methods to obtain blood samples from animals for parasite antibody evaluation. The DBS collection devices are compact, simple to use, and are particularly useful for large number of samples. Additionally, DBS samples take up less space and they are easier to transport than traditional venipuncture-collected blood samples. Visceral leishmaniasis (VL) is a potentially fatal parasitic disease of dogs and humans and it is frequently diagnosed by antibody tests. Immunochromatographic tests (ICT) for antibodies to Leishmania infantum are commercially available for dogs and they produce qualitative results in minutes. Measurement of canine antibodies to L. infantum with the ICT using traditional venipuncture has been validated previously, but the use of DBS samples has not been evaluated using this method. The purpose of the present study was to determine the ability of DBS samples to detect antibodies to L. infantum in dogs using a commercial ICT assay. One hundred plasma samples from dogs experimentally infected with the LIVT-1 strain of L. infantum were collected by venipuncture and frozen. Individual samples were thawed, and then 80 μl plasma (2 drops) was aliquotted onto the 8-spoked disk pad on individual DBS sample collection devices (HemaSpot™, Spot-On Sciences, Austin, TX), dried, and stored in the dark at room temperature. After one month and six months, respectively, 2 spokes of the 8 spokes of the disk pad of each DBS sample were removed and eluted in 200 μl PBS. The eluate was used to test for antibodies in the ICT and compared to ICT results using thawed plasma (same initial source). Sensitivity and specificity of the ICT using DBS were determined by using ICT results from traditional blood collection samples for comparison. After 1 month, DBS samples showed 100% sensitivity and specificity when compared to ICT results on thawed plasma samples collected by traditional venipuncture. After six months storage at room temperature, DBS samples demonstrated 79% sensitivity and 100% specificity compared to traditional blood collection. Results from this study indicate that dried blood spot collection may be a useful tool for screening dogs for antibodies to L. infantum with the ICT assay. Copyright © 2014 Elsevier B.V. All rights reserved.

47 CFR 101.1440 - MVDDS protection of DBS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... along with main beam azimuth and altitude orientation information, and description of the antenna... responsible for providing information they deem necessary for those entities who install all future DBS...

Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture.

PubMed

Iroh Tam, Pui-Ying; Hernandez-Alvarado, Nelmary; Schleiss, Mark R; Hassan-Hanga, Fatimah; Onuchukwu, Chuma; Umoru, Dominic; Obaro, Stephen K

2016-01-01

Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4-90.1%) and 62.5% (95% CI 24.5-91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens.

Fully automated determination of nicotine and its major metabolites in whole blood by means of a DBS online-SPE LC-HR-MS/MS approach for sports drug testing.

PubMed

Tretzel, Laura; Thomas, Andreas; Piper, Thomas; Hedeland, Mikael; Geyer, Hans; Schänzer, Wilhelm; Thevis, Mario

2016-05-10

Dried blood spots (DBS) represent a sample matrix collected under minimal-invasive, straightforward and robust conditions. DBS specimens have been shown to provide appropriate test material for different analytical disciplines, e.g., preclinical drug development, therapeutic drug monitoring, forensic toxicology and diagnostic analysis of metabolic disorders in newborns. However, the sample preparation has occasionally been reported as laborious and time consuming. In order to minimize the manual workload and to substantiate the suitability of DBS for high sample-throughput, the automation of sample preparation processes is of paramount interest. In the current study, the development and validation of a fully automated DBS extraction method coupled to online solid-phase extraction using the example of nicotine, its major metabolites nornicotine, cotinine and trans-3'-hydroxycotinine and the tobacco alkaloids anabasine and anatabine is presented, based on the rationale that the use of nicotine-containing products for performance-enhancing purposes has been monitored by the World Anti-Doping Agency (WADA) for several years. Automation-derived DBS sample extracts were directed online to liquid chromatography high resolution/high mass accuracy tandem mass spectrometry, and target analytes were determined with support of four deuterated internal standards. Validation of the method yielded precise (CV <7.5% for intraday and <12.3% for interday measurements) and linear (r(2)>0.998) results. The limit of detection was established at 5 ng mL(-1) for all studied compounds, the extraction recovery ranged from 25 to 44%, and no matrix effects were observed. To exemplify the applicability of the DBS online-SPE LC-MS/MS approach for sports drug testing purposes, the method was applied to authentic DBS samples obtained from smokers, snus users, and e-cigarette users. Statistical evaluation of the obtained results indicated differences in metabolic behavior depending on the route of administration (inhalative versus buccal absorption) in terms of the ratio of nicotine and nornicotine. Copyright © 2016 Elsevier B.V. All rights reserved.

Deep-Brain Stimulation for Basal Ganglia Disorders.

PubMed

Wichmann, Thomas; Delong, Mahlon R

2011-07-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

Selective distillation phenomenon in two-species Bose-Einstein condensates in open boundary optical lattices.

PubMed

Bai, Xiao-Dong; Zhang, Mei; Xiong, Jun; Yang, Guo-Jian; Deng, Fu-Guo

2015-11-24

We investigate the formation of discrete breathers (DBs) and the dynamics of the mixture of two-species Bose-Einstein condensates (BECs) in open boundary optical lattices using the discrete nonlinear Schrödinger equations. The results show that the coupling of intra- and interspecies interaction can lead to the existence of pure single-species DBs and symbiotic DBs (i.e., two-species DBs). Furthermore, we find that there is a selective distillation phenomenon in the dynamics of the mixture of two-species BECs. One can selectively distil one species from the mixture of two-species BECs and can even control dominant species fraction by adjusting the intra- and interspecies interaction in optical lattices. Our selective distillation mechanism may find potential application in quantum information storage and quantum information processing based on multi-species atoms.

Selective distillation phenomenon in two-species Bose-Einstein condensates in open boundary optical lattices

PubMed Central

Bai, Xiao-Dong; Zhang, Mei; Xiong, Jun; Yang, Guo-Jian; Deng, Fu-Guo

2015-01-01

We investigate the formation of discrete breathers (DBs) and the dynamics of the mixture of two-species Bose-Einstein condensates (BECs) in open boundary optical lattices using the discrete nonlinear Schrödinger equations. The results show that the coupling of intra- and interspecies interaction can lead to the existence of pure single-species DBs and symbiotic DBs (i.e., two-species DBs). Furthermore, we find that there is a selective distillation phenomenon in the dynamics of the mixture of two-species BECs. One can selectively distil one species from the mixture of two-species BECs and can even control dominant species fraction by adjusting the intra- and interspecies interaction in optical lattices. Our selective distillation mechanism may find potential application in quantum information storage and quantum information processing based on multi-species atoms. PMID:26597592

Direct broadcast satellite-audio, portable and mobile reception tradeoffs

NASA Technical Reports Server (NTRS)

Golshan, Nasser

1992-01-01

This paper reports on the findings of a systems tradeoffs study on direct broadcast satellite-radio (DBS-R). Based on emerging advanced subband and transform audio coding systems, four ranges of bit rates: 16-32 kbps, 48-64 kbps, 96-128 kbps and 196-256 kbps are identified for DBS-R. The corresponding grades of audio quality will be subjectively comparable to AM broadcasting, monophonic FM, stereophonic FM, and CD quality audio, respectively. The satellite EIRP's needed for mobile DBS-R reception in suburban areas are sufficient for portable reception in most single family houses when allowance is made for the higher G/T of portable table-top receivers. As an example, the variation of the space segment cost as a function of frequency, audio quality, coverage capacity, and beam size is explored for a typical DBS-R system.

Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

PubMed

Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

2014-06-01

In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Self-Report and Dry Blood Spot Measurement of Antiretroviral Medications as Markers of Adherence in Pregnant Women in Rural South Africa.

PubMed

Alcaide, Maria L; Ramlagan, Shandir; Rodriguez, Violeta J; Cook, Ryan; Peltzer, Karl; Weiss, Stephen M; Sifunda, Sibusiso; Jones, Deborah L

2017-07-01

Antiretroviral (ARV) adherence is essential to prevent mother-to-child transmission of HIV. This study compared self-reported adherence versus ARV detection in dried blood spots (DBS) among N = 392 HIV-infected pregnant women in South Africa (SA). Women completed two self-reported adherence measures [visual analog scale (VAS), AIDS Clinical Trials Group Adherence (ACTG)]. Adherence was 89% (VAS), 80% (ACTG), and 74% (DBS). Self-report measures marginally agreed with DBS (VAS: Kappa = 0.101, Area under the ROC curve (AUROC) = 0.543; ACTG: Kappa  = 0.081, AUROC = 0.538). Self-reported adherence was overestimated and agreement with DBS was poor. Validation of self-reported ARV adherence among pregnant HIV+ women in SA is needed.

Teens and Research.

PubMed

Neuhaus, Carolyn Plunkett

2016-10-01

On seeing promising results in a small number of patients, some researchers are conducting trials to determine whether deep brain stimulation (DBS) is an effective treatment for anorexia nervosa (AN). This article asks whether we should open enrollment in trials of DBS for AN to adolescents. Despite concerns about informed consent, parental consent, and unforeseeable psychological sequelae, the article concludes that the risks to anorexic adolescents associated with participation in trials of DBS are reasonable considering the substantial risks of not enrolling teens with AN in research on DBS. The seriousness of AN, its high incidence in teens, and serious shortfalls in the AN treatment literature point to the need for improved, evidence-based treatments for teens with AN. This unmet need generates an obligation on the part of researchers and physicians to promote and conduct research on AN in adolescents.

Use of Dried Blood Spots to Elucidate Full-Length Transmitted/Founder HIV-1 Genomes

PubMed Central

Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Tully, Damien C.; Ogilvie, Colin B.; Learn, Gerald H.; Allen, Todd M.; Heath, Sonya L.; Goepfert, Paul; Bar, Katharine J.

2016-01-01

Background Identification of HIV-1 genomes responsible for establishing clinical infection in newly infected individuals is fundamental to prevention and pathogenesis research. Processing, storage, and transportation of the clinical samples required to perform these virologic assays in resource-limited settings requires challenging venipuncture and cold chain logistics. Here, we validate the use of dried-blood spots (DBS) as a simple and convenient alternative to collecting and storing frozen plasma. Methods We performed parallel nucleic acid extraction, single genome amplification (SGA), next generation sequencing (NGS), and phylogenetic analyses on plasma and DBS. Results We demonstrated the capacity to extract viral RNA from DBS and perform SGA to infer the complete nucleotide sequence of the transmitted/founder (TF) HIV-1 envelope gene and full-length genome in two acutely infected individuals. Using both SGA and NGS methodologies, we showed that sequences generated from DBS and plasma display comparable phylogenetic patterns in both acute and chronic infection. SGA was successful on samples with a range of plasma viremia, including samples as low as 1,700 copies/ml and an estimated ∼50 viral copies per blood spot. Further, we demonstrated reproducible efficiency in gp160 env sequencing in DBS stored at ambient temperature for up to three weeks or at -20°C for up to five months. Conclusions These findings support the use of DBS as a practical and cost-effective alternative to frozen plasma for clinical trials and translational research conducted in resource-limited settings. PMID:27819061

Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

PubMed Central

Israelashvili, Michal; Loewenstern, Yocheved

2015-01-01

Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

Verbal Memory Decline following DBS for Parkinson’s Disease: Structural Volumetric MRI Relationships

PubMed Central

Geevarghese, Ruben; Lumsden, Daniel E.; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

2016-01-01

Background Parkinson’s disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Objectives Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. Methods A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. Results A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Conclusion Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes. PMID:27557088

Swallowing and deep brain stimulation in Parkinson's disease: a systematic review.

PubMed

Troche, Michelle S; Brandimore, Alexandra E; Foote, Kelly D; Okun, Michael S

2013-09-01

The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson's disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. "on" vs. "off", pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Swallowing and deep brain stimulation in Parkinson’s disease: A systematic review

PubMed Central

Troche, Michelle S.; Brandimore, Alexandra E.; Foote, Kelly D.; Okun, Michael S.

2013-01-01

The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson’s disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. “on” vs. “off”, pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. PMID:23726461

Hardware-related infections after deep brain stimulation surgery: review of incidence, severity and management in 212 single-center procedures in the first year after implantation.

PubMed

Piacentino, Massimo; Pilleri, Manuela; Bartolomei, Luigi

2011-12-01

Device-related infection is a common occurrence after deep brain stimulation (DBS) surgery, and may result in additional interventions and a loss of efficacy of therapy. This retrospective review aimed to evaluate the incidence, severity and management of device-related infections in 212 DBS procedures performed in our institute. Data on 106 patients, in whom 212 DBS procedures were performed between 2001 and 2011 at our institute by a single neurosurgeon (M.P.), were reviewed to assess the incidence, severity, management and clinical characteristics of infections in the first year after the implantation of a DBS system. Infections occurred in 8.5% of patients and 4.2% of procedures. Of the nine infections, eight involved the neurostimulator and extensions, and one the whole system. The infections occurred 30.7 days after implantation: 7 within 30 days and 2 within 6 months. Infected and uninfected patients were comparable in terms of age, sex, indication for DBS implantation and neurostimulator location. In eight cases, the system components involved were removed and re-implanted after 3 months, while in one case the complete hardware was removed and not re-implanted. The overall incidence of postoperative infections after DBS system implantation was 4.2%; this rate decreased over time. All infections required further surgery. Correct and timely management of partial infections may result in successful salvage of part of the system.

Anatomic Connections of the Subgenual Cingulate Region.

PubMed

Vergani, Francesco; Martino, Juan; Morris, Christopher; Attems, Johannes; Ashkan, Keyoumars; DellʼAcqua, Flavio

2016-09-01

The subgenual cingulate gyrus (SCG) has been proposed as a target for deep brain stimulation (DBS) in neuropsychiatric disorders, mainly major depression. Despite promising clinical results, the mechanism of action of DBS in this region is poorly understood. Knowledge of the connections of the SCG can elucidate the network involved by DBS in this area and can help refine the targeting for DBS electrode placement. To investigate the anatomic connections of the SCG region. An anatomic study of the connections of the SCG was performed on postmortem specimens and in vivo with MR diffusion imaging tractography. Postmortem dissections were performed according to the Klingler technique. Specimens were fixed in 10% formalin and frozen at -15°C for 2 weeks. After thawing, dissection was performed with blunt dissectors. Whole brain tractography was performed using spherical deconvolution tractography. Four main connections were found: (1) fibers of the cingulum, originating at the level of the SCG and terminating at the medial aspect of the temporal lobe (parahippocampal gyrus); (2) fibers running toward the base of the frontal lobe, connecting the SCG with frontopolar areas; (3) fibers running more laterally, converging onto the ventral striatum (nucleus accumbens); (4) fibers of the uncinate fasciculus, connecting the orbitofrontal with the anterior temporal region. The SCG shows a wide range of white matter connections with limbic, prefrontal, and mesiotemporal areas. These findings can help to explain the role of the SCG in DBS for psychiatric disorders. DBS, deep brain stimulationSCG, subgenual cingulate gyrus.

Subthalamic deep brain stimulation in Parkinson׳s disease has no significant effect on perceptual timing in the hundreds of milliseconds range.

PubMed

Cope, Thomas E; Grube, Manon; Mandal, Arnab; Cooper, Freya E; Brechany, Una; Burn, David J; Griffiths, Timothy D

2014-05-01

Bilateral, high-frequency stimulation of the basal ganglia (STN-DBS) is in widespread use for the treatment of the motor symptoms of Parkinson׳s disease (PD). We present here the first psychophysical investigation of the effect of STN-DBS upon perceptual timing in the hundreds of milliseconds range, with both duration-based (absolute) and beat-based (relative) tasks; 13 patients with PD were assessed with their STN-DBS 'on', 'off', and then 'on' again. Paired parametric analyses revealed no statistically significant differences for any task according to DBS status. We demonstrate, from the examination of confidence intervals, that any functionally relevant effect of STN-DBS on relative perceptual timing is statistically unlikely. For absolute, duration-based timing, we demonstrate that the activation of STN-DBS may either worsen performance or have no effect, but that it is unlikely to lead to significant improvement. Although these results are negative they have important implications for our understanding of perceptual timing and its relationship to motor functions within the timing network of the brain. They imply that the mechanisms involved in the perceptual processing of temporal information are likely to be functionally independent from those that underpin movement. Further, they suggest that the connections between STN and the subtantia nigra and globus pallidus are unlikely to be critical to beat-based perceptual timing. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Deep brain stimulation and spinal cord stimulation for vegetative state and minimally conscious state.

PubMed

Yamamoto, Takamitsu; Katayama, Yoichi; Obuchi, Toshiki; Kobayashi, Kazutaka; Oshima, Hideki; Fukaya, Chikashi

2013-01-01

On the basis of the findings of the electrophysiological evaluation of vegetative state (VS) and minimally conscious state (MCS), the effect of deep brain stimulation (DBS) was examined according to long-term follow-up results. The results of spinal cord stimulation (SCS) on MCS was also examined and compared with that of DBS. One hundred seven patients in VS and 21 patients in MCS were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury. Among the 107 VS patients, 21 were treated by DBS. Among the 21 MCS patients, 5 were treated by DBS and 10 by SCS. Eight of the 21 patients recovered from VS and were able to follow verbal instructions. These eight patients showed desynchronization on continuous electroencephalographic frequency analysis. The Vth wave of the auditory brainstem response and N20 of somatosensory evoked potential were recorded even with a prolonged latency, and pain-related P250 was recorded with an amplitude of more than 7 μV. In addition, DBS and SCS induced a marked functional recovery in MCS patients who satisfied the electrophysiological inclusion criteria. DBS for VS and MCS patients and SCS for MCS patients may be useful, when the candidates are selected on the basis of the electrophysiological inclusion criteria. Only 16 (14.9%) of the 107 VS patients and 15 (71.4%) of the 21 MCS patients satisfied the electrophysiological inclusion criteria. Copyright © 2013 Elsevier Inc. All rights reserved.

Optimized DNA extraction from neonatal dried blood spots: application in methylome profiling

PubMed Central

2014-01-01

Background Neonatal dried blood spots (DBS) represent an inexpensive method for long-term biobanking worldwide and are considered gold mines for research for several human diseases, including those of metabolic, infectious, genetic and epigenetic origin. However, the utility of DBS is restricted by the limited amount and quality of extractable biomolecules (including DNA), especially for genome wide profiling. Degradation of DNA in DBS often occurs during storage and extraction. Moreover, amplifying small quantities of DNA often leads to a bias in subsequent data, particularly in methylome profiles. Thus it is important to develop methodologies that maximize both the yield and quality of DNA from DBS for downstream analyses. Results Using combinations of in-house-derived and modified commercial extraction kits, we developed a robust and efficient protocol, compatible with methylome studies, many of which require stringent bisulfite conversion steps. Several parameters were tested in a step-wise manner, including blood extraction, cell lysis, protein digestion, and DNA precipitation, purification and elution. DNA quality was assessed based on spectrophotometric measurements, DNA detectability by PCR, and DNA integrity by gel electrophoresis and bioanalyzer analyses. Genome scale Infinium HumanMethylation450 and locus-specific pyrosequencing data generated using the refined DBS extraction protocol were of high quality, reproducible and consistent. Conclusions This study may prove useful to meet the increased demand for research on prenatal, particularly epigenetic, origins of human diseases and for newborn screening programs, all of which are often based on DNA extracted from DBS. PMID:24980254

Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

PubMed

Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

2017-02-01

Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

Panic and fear induced by deep brain stimulation.

PubMed

Shapira, N A; Okun, M S; Wint, D; Foote, K D; Byars, J A; Bowers, D; Springer, U S; Lang, P J; Greenberg, B D; Haber, S N; Goodman, W K

2006-03-01

Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region. To investigate panic and fear resulting from DBS. Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions. DBS at the distal (0) contact (cathode 0-, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off condition DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks.

Ultra-high magnetic resonance imaging (MRI): a potential examination for deep brain stimulation devices and the limitation study concerning MRI-related heating injury.

PubMed

Chen, Ying-Chuan; Li, Jun-Ju; Zhu, Guan-Yu; Shi, Lin; Yang, An-Chao; Jiang, Yin; Zhang, Xin; Zhang, Jian-Guo

2017-03-01

Nowadays, the patients with deep brain stimulation (DBS) devices are restricted to undertake 1.5T magnetic resonance imaging (MRI) according to the guideline. Nevertheless, we conducted an experiment to test pathological change near the leads in different field-strength MRI. Twenty-four male New Zealand rabbits were assigned to Group 1 (G1, n = 6, 7.0T, DBS), Group 2 (G2, n = 6, 3.0T, DBS), Group 3 (G3, n = 6, 1.5T, DBS), and Group 4 (G4, n = 6, 1.5T, paracentesis). DBS leads were implanted in G1, G2 and G3, targeting left nucleus ventralis posterior thalami. Paracentesis was performed in G4. 24 h after MRI scan, all animals were killed for examining pathological alternation (at different distance from lead) via transmission electron microscopy. Our results suggest that the severity of tissue injury correlates with the distance to electrode instead of field strength of MRI. Up to now, the reason for the restriction of MRI indicated no significantly different pathological change.

Surgery for Dystonia and Tremor.

PubMed

Crowell, Jason L; Shah, Binit B

2016-03-01

Surgical procedures for dystonia and tremor have evolved over the past few decades, and our understanding of risk, benefit, and predictive factors has increased substantially in that time. Deep brain stimulation (DBS) is the most utilized surgical treatment for dystonia and tremor, though lesioning remains an effective option in appropriate patients. Dystonic syndromes that have shown a substantial reduction in severity secondary to DBS are isolated dystonia, including generalized, cervical, and segmental, as well as acquired dystonia such as tardive dystonia. Essential tremor is quite amenable to DBS, though the response of other forms of postural and kinetic tremor is not nearly as robust or consistent based on available evidence. Regarding targeting, DBS lead placement in the globus pallidus internus has shown marked efficacy in dystonia reduction. The subthalamic nucleus is an emerging target, and increasing evidence suggests that this may be a viable target in dystonia as well. The ventralis intermedius nucleus of the thalamus is the preferred target for essential tremor, though targeting the subthalamic zone/caudal zona incerta has shown promise and may emerge as another option in essential tremor and possibly other tremor disorders. In the carefully selected patient, DBS and lesioning procedures are relatively safe and effective for the management of dystonia and tremor.

Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS?

PubMed

Taylor, Joseph J; Krystal, John H; D'Souza, Deepak C; Gerrard, Jason Lee; Corlett, Philip R

2018-05-01

The debilitating and refractory nature of auditory hallucinations (AH) in schizophrenia and other psychiatric disorders has stimulated investigations into neuromodulatory interventions that target the aberrant neural networks associated with them. Internal or invasive forms of brain stimulation such as deep brain stimulation (DBS) are currently being explored for treatment-refractory schizophrenia. The process of developing and implementing DBS is limited by symptom clustering within psychiatric constructs as well as a scarcity of causal tools with which to predict response, refine targeting or guide clinical decisions. Transcranial magnetic stimulation (TMS), an external or non-invasive form of brain stimulation, has shown some promise as a therapeutic intervention for AH but remains relatively underutilized as an investigational probe of clinically relevant neural networks. In this editorial, we propose that TMS has the potential to inform DBS by adding individualized causal evidence to an evaluation processes otherwise devoid of it in patients. Although there are significant limitations and safety concerns regarding DBS, the combination of TMS with computational modeling of neuroimaging and neurophysiological data could provide critical insights into more robust and adaptable network modulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Microwave-assisted on-spot derivatization for gas chromatography-mass spectrometry based determination of polar low molecular weight compounds in dried blood spots.

PubMed

Sadones, Nele; Van Bever, Elien; Archer, John R H; Wood, David M; Dargan, Paul I; Van Bortel, Luc; Lambert, Willy E; Stove, Christophe P

2016-09-23

Dried blood spot (DBS) sampling and analysis is increasingly being applied in bioanalysis. Although the use of DBS has many advantages, it is also associated with some challenges. E.g. given the limited amount of available material, highly sensitive detection techniques are often required to attain sufficient sensitivity. In gas chromatography coupled to mass spectrometry (GC-MS), derivatization can be helpful to achieve adequate sensitivity. Because this additional sample preparation step is considered as time-consuming, we introduce a new derivatization procedure, i.e. "microwave-assisted on-spot derivatization", to minimize sample preparation of DBS. In this approach the derivatization reagents are directly applied onto the DBS and derivatization takes place in a microwave instead of via conventional heating. In this manuscript we evaluated the applicability of this new concept of derivatization for the determination of two polar low molecular weight molecules, gamma-hydroxybutyric acid (GHB) and gabapentin, in DBS using a standard GC-MS configuration. The method was successfully validated for both compounds, with imprecision and bias values within acceptance criteria (<20% at LLOQ, <15% at 3 other QC levels). Calibration lines were linear over the 10-100μg/mL and 1-30μg/mL range for GHB and gabapentin, respectively. Stability studies revealed no significant decrease of gabapentin and GHB in DBS upon storage at room temperature for at least 84 days. Furthermore, DBS-specific parameters, including hematocrit and volume spotted, were evaluated. As demonstrated by the analysis of GHB and gabapentin positive samples, "microwave-assisted on-spot derivatization" proved to be reliable, fast and applicable in routine toxicology. Moreover, other polar low molecular weight compounds of interest in clinical and/or forensic toxicology, including vigabatrin, beta-hydroxybutyric acid, propylene glycol, diethylene glycol, 1,4-butanediol and 1,2-butanediol, can also be detected using this method. Copyright © 2016 Elsevier B.V. All rights reserved.

A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease.

PubMed

Kumaravelu, Karthik; Brocker, David T; Grill, Warren M

2016-04-01

Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG.

Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

PubMed

Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

2016-01-01

Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.

Thalamic deep brain stimulation for writer's cramp.

PubMed

Fukaya, Chikashi; Katayama, Yoichi; Kano, Toshikazu; Nagaoka, Takafumi; Kobayashi, Kazutaka; Oshima, Hideki; Yamamoto, Takamitsu

2007-11-01

Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. In this report, the authors describe the clinical outcome after thalamic deep brain stimulation (DBS) therapy in patients with writer's cramp and present an illustrative case with which they compare the effects of pallidal and thalamic stimulation. In addition to these results for the clinical effectiveness, they also examine the best point and pattern for therapeutic stimulation of the motor thalamus, including the nucleus ventrooralis (VO) and the ventralis intermedius nucleus (VIM), for writer's cramp. The authors applied thalamic DBS in five patients with writer's cramp. The inclusion criteria for the DBS trial in this disorder were a diagnosis of idiopathic writer's cramp and the absence of a positive response to medication. The exclusion criteria included significant cognitive dysfunction, active psychiatric symptoms, and evidence of other central nervous system diseases or other medical disorders. In one of the cases, DBS leads were implanted into both the globus pallidus internus and the VO/VIM, and test stimulation was performed for 1 week. The authors thus had an opportunity to compare the effects of pallidal and thalamic stimulation in this patient. Immediately after the initiation of thalamic stimulation, the neurological deficits associated with writer's cramp were improved in all five cases. Postoperatively all preoperative scale scores indicating the seriousness of the writer's cramp were significantly lower (p < 0.001). In the patient in whom two DBS leads were implanted, the clinical effect of thalamic stimulation was better than that of pallidal stimulation. During the thalamic stimulation, the maximum effect was obtained when stimulation was applied to both the VO and the VIM widely, compared with being applied only within the VO. The authors successfully treated patients with writer's cramp by thalamic DBS. Insofar as they are aware, this is the first series in which writer's cramp has been treated with DBS. Thalamic stimulation appears to be a safe and valuable therapeutic option for writer's cramp.

Quantification of phosphatidylethanol 16:0/18:1, 18:1/18:1, and 16:0/16:0 in venous blood and venous and capillary dried blood spots from patients in alcohol withdrawal and control volunteers.

PubMed

Kummer, Natalie; Ingels, Ann-Sofie; Wille, Sarah M R; Hanak, Catherine; Verbanck, Paul; Lambert, Willy E E; Samyn, Nele; Stove, Christophe P

2016-01-01

Phosphatidylethanol species (PEths) are promising biomarkers of alcohol consumption. Here, we report on the set-up, validation, and application of a novel UHPLC-ESI-MS/MS method for the quantification of PEth 16:0/18:1, PEth 18:1/18:1, and PEth 16:0/16:0 in whole blood (30 μL) and in venous (V, 30 μL) or capillary (C, 3 punches (3 mm)) dried blood spots (DBS). The methods were linear from 10 (LLOQ) to 2000 ng/mL for PEth 16:0/18:1, from 10 (LLOQ) to 1940 ng/mL for PEth 18:1/18:1, and from 19 (LLOQ) to 3872 ng/mL for PEth 16:0/16:0. Extraction efficiencies were higher than 55% (RSD < 18%) and matrix effects compensated for by IS were between 77 and 125% (RSD < 10%). Accuracy, repeatability, and intermediate precision fulfilled acceptance criteria (bias and RSD below 13%). Validity of the procedure for determination of PEth 16:0/18:1 in blood was demonstrated by the successful participation in a proficiency test. The quantification of PEths in C-DBS was not significantly influenced by the hematocrit, punch localization, or spot volume. The stability of PEths in V-DBS stored at room temperature was demonstrated up to 6 months. The method was applied to authentic samples (whole blood, V-DBS, and C-DBS) from 50 inpatients in alcohol withdrawal and 50 control volunteers. Applying a cut-off value to detect inpatients at 221 ng/mL for PEth 16:0/18:1 provided no false positive results and a good sensitivity (86%). Comparison of quantitative results (Bland-Altman plot, Passing-Bablok regression, and Wilcoxon signed rank test) revealed that V-DBS and C-DBS were valid alternatives to venous blood for the detection of alcohol consumption.

Simultaneous determination of pentoxifylline, metabolites M1 (lisofylline), M4 and M5, and caffeine in plasma and dried blood spots for pharmacokinetic studies in preterm infants and neonates.

PubMed

Page-Sharp, Madhu; Strunk, Tobias; Salman, Sam; Hibbert, Julie; Patole, Sanjay K; Manning, Laurens; Batty, Kevin T

2017-11-30

Advances in bioanalytical methods are facilitating micro-volume and dried blood spot (DBS) analysis of drugs in biological matrices for pharmacokinetic studies in children and neonates. We sought to develop a UPLC-MS/MS assay for simultaneous measurement of caffeine, pentoxifylline (PTX) and three metabolites of PTX in both plasma and DBS. Caffeine, PTX, the metabolites M1 (lisofylline), M4 and M5, and the internal standards (caffeine-d 9 and PTX-d 6 ) were separated using a Waters Aquity T3 UPLC C 18 column and gradient mobile phase (water-methanol-formic acid). Retention times for caffeine, M5, M4, PTX and M1 were 1.6, 1.7, 1.9, 2.0 and 2.1min, respectively, with a run time of 5min. The precision (≤10%) and accuracy (≤15%) across the concentration range 0.1-50mg/L for caffeine, PTX and the three metabolites in plasma and DBS were within accepted limits, as were the limits of quantification (100μg/L for caffeine and 10μg/L for PTX, M1, M4 and M5). Caffeine, PTX and the metabolites were stable in DBS for >34days at room and refrigerated temperatures. Plasma and DBS samples were obtained from 24 preterm infants recruited into a clinical pharmacokinetic study of PTX. Paired analysis indicated that DBS concentrations were 9% lower than concurrent plasma concentrations for caffeine, 7% lower for PTX (consistent with the blood:plasma ratio) and 13% lower for M1 (lisofylline). The validated UPLC-MS/MS method is suitable for micro-volume plasma and DBS analysis of caffeine, PTX and its metabolites for pharmacokinetic studies in paediatric patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effect of Uni- and Bilateral Thalamic Deep Brain Stimulation on Speech in Patients With Essential Tremor: Acoustics and Intelligibility.

PubMed

Becker, Johannes; Barbe, Michael T; Hartinger, Mariam; Dembek, Till A; Pochmann, Jil; Wirths, Jochen; Allert, Niels; Mücke, Doris; Hermes, Anne; Meister, Ingo G; Visser-Vandewalle, Veerle; Grice, Martine; Timmermann, Lars

2017-04-01

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is performed to suppress medically-resistant essential tremor (ET). However, stimulation induced dysarthria (SID) is a common side effect, limiting the extent to which tremor can be suppressed. To date, the exact pathogenesis of SID in VIM-DBS treated ET patients is unknown. We investigate the effect of inactivated, uni- and bilateral VIM-DBS on speech production in patients with ET. We employ acoustic measures, tempo, and intelligibility ratings and patient's self-estimated speech to quantify SID, with a focus on comparing bilateral to unilateral stimulation effects and the effect of electrode position on speech. Sixteen German ET patients participated in this study. Each patient was acoustically recorded with DBS-off, unilateral-right-hemispheric-DBS-on, unilateral-left-hemispheric-DBS-on, and bilateral-DBS-on during an oral diadochokinesis task and a read German standard text. To capture the extent of speech impairment, we measured syllable duration and intensity ratio during the DDK task. Naïve listeners rated speech tempo and speech intelligibility of the read text on a 5-point-scale. Patients had to rate their "ability to speak". We found an effect of bilateral compared to unilateral and inactivated stimulation on syllable durations and intensity ratio, as well as on external intelligibility ratings and patients' VAS scores. Additionally, VAS scores are associated with more laterally located active contacts. For speech ratings, we found an effect of syllable duration such that tempo and intelligibility was rated worse for speakers exhibiting greater syllable durations. Our data confirms that SID is more pronounced under bilateral compared to unilateral stimulation. Laterally located electrodes are associated with more severe SID according to patient's self-ratings. We can confirm the relation between diadochokinetic rate and SID in that listener's tempo and intelligibility ratings can be predicted by measured syllable durations from DDK tasks. © 2017 International Neuromodulation Society.

Bilateral globus pallidus internus deep brain stimulation for dyskinetic cerebral palsy supports success of cochlear implantation in a 5-year old ex-24 week preterm twin with absent cerebellar hemispheres.

PubMed

Lin, Jean-Pierre; Kaminska, Margaret; Perides, Sarah; Gimeno, Hortensia; Baker, Lesley; Lumsden, Daniel E; Britz, Anzell; Driver, Sandra; Fitzgerald-O'Connor, Alec; Selway, Richard

2017-01-01

Early onset dystonia (dyskinesia) and deafness in childhood pose significant challenges for children and carers and are the cause of multiple disability. It is particularly tragic when the child cannot make use of early cochlear implantation (CI) technology to relieve deafness and improve language and communication, because severe cervical and truncal dystonia brushes off the magnetic amplifier behind the ears. Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) neuromodulation can reduce dyskinesia, thus supporting CI neuromodulation success. We describe the importance of the order of dual neuromodulation surgery for dystonia and deafness. First with bilateral GPi DBS using a rechargeable ACTIVA-RC neurostimulator followed 5 months later by unilateral CI with a Harmony (BTE) Advanced Bionics Hi Res 90 K cochlear device. This double neuromodulation was performed in series in a 12.5 kg 5 year-old ex-24 week gestation-born twin without a cerebellum. Relief of dyskinesia enabled continuous use of the CI amplifier. Language understanding and communication improved. Dystonic storms abated. Tolerance of sitting increased with emergence of manual function. Status dystonicus ensued 10 days after ACTIVA-RC removal for infection-erosion at 3 years and 10 months. He required intensive care and DBS re-implantation 3 weeks later together with 8 months of hospital care. Today he is virtually back to the level of functioning before the DBS removal in 2012 and background medication continues to be slowly weaned. This case illustrates that early neuromodulation with DBS for dystonic cerebral palsy followed by CI for deafness is beneficial. Both should be considered early i.e. under the age of five years. The DBS should precede the CI to maximise dystonia reduction and thus benefits from CI. This requires close working between the paediatric DBS and CI services. Copyright © 2016. Published by Elsevier Ltd.

Economic Analysis of Deep Brain Stimulation in Parkinson Disease: Systematic Review of the Literature.

PubMed

Becerra, Jaime Eduardo; Zorro, Oscar; Ruiz-Gaviria, Rafael; Castañeda-Cardona, Camilo; Otálora-Esteban, Margarita; Henao, Sara; Navarrete, Sergio; Acevedo, Juan Carlos; Rosselli, Diego

2016-09-01

Parkinson disease (PD) is a chronic multifaceted neurodegenerative disorder of adult onset that affects quality of life and places a burden on patients, caregivers, and society. In early disease, dopaminergic therapy improves motor symptoms, but as the disease progresses, symptoms tend to increase in frequency and severity, even with best medical treatment (BMT). Deep brain stimulation (DBS) becomes an option for certain patients, but cost becomes an important issue. We performed a systematic review of the literature of economic studies of the use of DBS in patients with PD, including costs studies or economic evaluations expressed as cost per improvement in quality life, decrease in dose of pharmacological treatments, and the decrease of caregiver burden. We reviewed the following databases: Medline/PubMed, Embase, Cochrane Database of Systematic Reviews, LILACS, Cochrane Central Register of Controlled Trials, WHO International Clinical Trials Registry Platform ICTRP portal and ClinicalTrials.gov from 1980 to 2015. Costs have been converted or adjusted to 2016 US dollars (US$). Nine studies were identified. The average cost of DBS for a patient with PD in 5 years is US$186,244. The quality-adjusted life year was higher in DBS compared with BMT after at least 2 years of treatment, with an average incremental cost utility ratio of US$41,932 per additional quality-adjusted life year gained. Costs in the first year are higher with DBS because of direct costs related to the surgical procedure, the device, and the more frequent controls. Studies show better results with a longer time horizon (up to 5 years). DBS is a cost-effective intervention for patients with advanced PD, but it has a high initial cost compared with BMT. However, DBS reduces pharmacologic treatment costs and should also reduce direct, indirect, and social costs of PD on the long term. Copyright © 2016 Elsevier Inc. All rights reserved.

Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease.

PubMed

Drapier, Sophie; Raoul, Sylvie; Drapier, Dominique; Leray, Emmanuelle; Lallement, François; Rivier, Isabelle; Sauleau, Paul; Lajat, Youen; Edan, Gilles; Vérin, Marc

2005-05-01

The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown. To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease. The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS. Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved. Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.

Stability and Application of Reactive Nitrogen and Oxygen Species-Induced Hemoglobin Modifications in Dry Blood Spots As Analyzed by Liquid Chromatography Tandem Mass Spectrometry.

PubMed

Chen, Hauh-Jyun Candy; Fan, Chih-Huang; Yang, Ya-Fen

2016-12-19

Dried blood spot (DBS) is an emerging microsampling technique for the bioanalysis of small molecules, including fatty acids, metabolites, drugs, and toxicants. DBS offers many advantages as a sample format including easy sample collection and cheap sample shipment. Hemoglobin adducts have been recognized as a suitable biomarker for monitoring chemical exposure. We previously reported that certain modified peptides in hemoglobin derived from reactive chlorine, nitrogen, and oxygen species are associated with factors including smoking, diabetes mellitus, and aging. However, the stability of these oxidation-induced modifications of hemoglobin remains unknown and whether they can be formed artifactually during storage of DBS. To answer these questions, globin extracted from the DBS cards was analyzed, and the stability of the modifications was evaluated. After storage of the DBS cards at 4 °C or room temperature up to 7 weeks, we isolated globin from a quarter of the spot every week. The extents of 11 sites and types of post-translational modifications (PTMs), including nitration and nitrosylation of tyrosine and oxidation of cysteine and methionine residues, in human hemoglobin were measured in the trypsin digest by nanoflow liquid chromatography-nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS) using selected reaction monitoring. The extents of all these PTMs are stable within 14 days when stored on DBS at room temperature and at 4 °C, while those from direct extraction of fresh blood are stable for at least 8 weeks when stored as an aqueous solution at -20 °C. Extraction of globin from a DBS card is of particular importance for hemolytic blood samples. To our knowledge, this is the first report on the stability of oxidative modifications of hemoglobin on DBSs, which are stable for 14 days under ambient conditions (room temperature, in air). Therefore, it is feasible and convenient to analyze these hemoglobin modifications from DBSs in studies involving large populations.

Transverse discrete breathers in unstrained graphene

NASA Astrophysics Data System (ADS)

Barani, Elham; Lobzenko, Ivan P.; Korznikova, Elena A.; Soboleva, Elvira G.; Dmitriev, Sergey V.; Zhou, Kun; Marjaneh, Aliakbar Moradi

2017-02-01

Discrete breathers (DB) are spatially localized vibrational modes of large amplitude in defect-free nonlinear lattices. The search for DBs in graphene is of high importance, taking into account that this one atom thick layer of carbon is promising for a number of applications. There exist several reports on successful excitation of DBs in graphene, based on molecular dynamics and ab initio simulations. In a recent work by Hizhnyakov with co-authors the possibility to excite a DB with atoms oscillating normal to the graphene sheet has been reported. In the present study we use a systematic approach for finding initial conditions to excite transverse DBs in graphene. The approach is based on the analysis of the frequency-amplitude dependence for a delocalized, short-wavelength vibrational mode. This mode is a symmetry-dictated exact solution to the dynamic equations of the atomic motion, regardless the mode amplitude and regardless the type of interatomic potentials used in the simulations. It is demonstrated that if the AIREBO potential is used, the mode frequency increases with the amplitude bifurcating from the upper edge of the phonon spectrum for out-of-plane phonons. Then a bell-shaped function is superimposed on this delocalized mode to obtain a spatially localized vibrational mode, i.e., a DB. Placing the center of the bell-shaped function at different positions with respect to the lattice sites, three different DBs are found. Typically, the degree of spatial localization of DBs increases with the DB amplitude, but the transverse DBs in graphene reported here demonstrate the opposite trend. The results are compared to those obtained with the use of the Savin interatomic potential and no transverse DBs are found in this case. The results of this study contribute to a better understanding of the nonlinear dynamics of graphene and they call for the ab initio simulations to verify which of the two potentials used in this study is more precise.

Brain stimulation in posttraumatic stress disorder

PubMed Central

Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A.B.; Mindes, Janet; A.Golier, Julia; Yehuda, Rachel

2011-01-01

Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. PMID:22893803

Psychometric Evaluation of the HIV Disclosure Belief Scale: A Rasch Model Approach.

PubMed

Hu, Jinxiang; Serovich, Julianne M; Chen, Yi-Hsin; Brown, Monique J; Kimberly, Judy A

2017-01-01

This study provides psychometric assessment of an HIV disclosure belief scale (DBS) among men who have sex with men (MSM). This study used baseline data from a clinical trial evaluating the effectiveness of an HIV serostatus disclosure intervention of 338 HIV-positive MSM. The Rasch model was used after unidimensionality and local independence assumptions were tested for application of the model. Results suggest that there was only one item that did not fit the model well. After removing the item, the DBS showed good model-data fit and high item and person reliabilities. This instrument showed measurement invariance across two different age groups, but some items showed differential item functioning between Caucasian and other minority groups. The findings suggest that the DBS is suitable for measuring the HIV disclosure beliefs, but it should be cautioned when the DBS is used to compare the disclosure beliefs between different racial/ethnic groups.

Deep-Brain Stimulation for Basal Ganglia Disorders

PubMed Central

Wichmann, Thomas; DeLong, Mahlon R.

2011-01-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders. PMID:21804953

Automated DBS microsampling, microscale automation and microflow LC-MS for therapeutic protein PK.

PubMed

Zhang, Qian; Tomazela, Daniela; Vasicek, Lisa A; Spellman, Daniel S; Beaumont, Maribel; Shyong, BaoJen; Kenny, Jacqueline; Fauty, Scott; Fillgrove, Kerry; Harrelson, Jane; Bateman, Kevin P

2016-04-01

Reduce animal usage for discovery-stage PK studies for biologics programs using microsampling-based approaches and microscale LC-MS. We report the development of an automated DBS-based serial microsampling approach for studying the PK of therapeutic proteins in mice. Automated sample preparation and microflow LC-MS were used to enable assay miniaturization and improve overall assay throughput. Serial sampling of mice was possible over the full 21-day study period with the first six time points over 24 h being collected using automated DBS sample collection. Overall, this approach demonstrated comparable data to a previous study using single mice per time point liquid samples while reducing animal and compound requirements by 14-fold. Reduction in animals and drug material is enabled by the use of automated serial DBS microsampling for mice studies in discovery-stage studies of protein therapeutics.

Surgical treatment of Parkinson’s disease: Past, present, and future

PubMed Central

Duker, Andrew P.; Espay, Alberto J.

2013-01-01

Advances in functional neurosurgery have expanded the treatment of Parkinson’s disease (PD), from early lesional procedures to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients with Parkinson’s disease (PD) and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Outcomes for DBS targeting the two major studied targets in PD, the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi), appear to be broadly similar and the choice is best made based on individual patient factors and surgeon preference. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus (PPN) stimulation for treatment of freezing and falls, the utilization of pathologic oscillations in the beta band to construct an adaptive “closed-loop” DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations. PMID:23896506

Dried blood spots analysis with mass spectrometry: Potentials and pitfalls in therapeutic drug monitoring.

PubMed

Antunes, Marina Venzon; Charão, Mariele Feiffer; Linden, Rafael

2016-09-01

Therapeutic drug monitoring (TDM) relays in the availability of specialized laboratory assays, usually available in reference centers that are not accessible to all patients. In this context, there is a growing interest in the use of dried blood spot (DBS) sampling, usually obtained from finger pricks, which allows simple and cost-effective logistics in many settings, particularly in Developing Countries. The use of DBS assays to estimate plasma concentrations is highly dependent on the hematocrit of the blood, as well as the particular characteristics of the measured analyte. DBS assays require specific validation assays, most of them are related to hematocrit effects. In the present manuscript, the application of mass spectrometric assays for determination of drugs for TDM purposes in the last ten years is reviewed, as well as the particular validation assays for new DBS methods. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Successful deep brain stimulation surgery with intraoperative magnetic resonance imaging on a difficult neuroacanthocytosis case: case report.

PubMed

Lim, Thien Thien; Fernandez, Hubert H; Cooper, Scott; Wilson, Kathryn Mary K; Machado, Andre G

2013-07-01

Chorea acanthocytosis is a progressive hereditary neurodegenerative disorder characterized by hyperkinetic movements, seizures, and acanthocytosis in the absence of any lipid abnormality. Medical treatment is typically limited and disappointing. We report on a 32-year-old patient with chorea acanthocytosis with a failed attempt at awake deep brain stimulation (DBS) surgery due to intraoperative seizures and postoperative intracranial hematoma. He then underwent a second DBS operation, but under general anesthesia and with intraoperative magnetic resonance imaging guidance. Marked improvement in his dystonia, chorea, and overall quality of life was noted 2 and 8 months postoperatively. DBS surgery of the bilateral globus pallidus pars interna may be useful in controlling the hyperkinetic movements in neuroacanthocytosis. Because of the high propensity for seizures in this disorder, DBS performed under general anesthesia, with intraoperative magnetic resonance imaging guidance, may allow successful implantation while maintaining accurate target localization.

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

PubMed

Nora, Tommi; Heinonen, Hanna; Tenhunen, Mirja; Rainesalo, Sirpa; Järvenpää, Soila; Lehtimäki, Kai; Peltola, Jukka

2018-01-01

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

Deep brain stimulation for disorders of consciousness: Systematic review of cases and ethics.

PubMed

Vanhoecke, Jonathan; Hariz, Marwan

A treatment for patients suffering from prolonged severely altered consciousness is not available. The success of Deep Brain Stimulation (DBS) in diseases such as Parkinson's, dystonia and essential tremor provided a renewed impetus for its application in Disorders of Consciousness (DoC). To evaluate the rationale for DBS in patients with DoC, through systematic review of literature containing clinical data and ethical considerations. Articles from PubMed, Embase, Medline and Web of Science were systematically reviewed. The outcomes of 78 individual patients reported in 19 articles from 1968 onwards were pooled and elements of ethical discussions were compared. There is no clear clinical evidence that DBS is a treatment for DoC that can restore both consciousness and the ability to communicate. In patients who benefitted, the outcome of DBS is often confounded by the time frame of spontaneous recovery from DoC. Difficult ethical considerations remain, such as the risk of increasing self-awareness of own limitations, without improving overall wellbeing, and the issues of proxy consent. DBS is far from being evident as a possible future therapeutic avenue for patients with DoC. Double-blind studies are lacking, and many clinical and ethical issues have to be addressed. In the rare cases when DBS for patients with DoC is considered, this needs to be evaluated meticulously on a case by case basis, with comprehensive overall outcome measures including psychological and quality-of-life assessments, and with the guidance of an ethical and interdisciplinary panel, especially in relation to proxy consent. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator.

PubMed

Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Min, Hoon-Ki; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

2013-06-01

To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0-T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5 T and, at both field strengths, in a phantom. At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in vivo heating differed from those obtained in the phantom. The 3.0-T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46 °C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0-T MRI in patients with DBS. Copyright © 2013 Elsevier Inc. All rights reserved.

Dried blood spot measurement of pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin (β-hCG) from a low-resource setting.

PubMed

Browne, J L; Schielen, P C J I; Belmouden, I; Pennings, J L A; Klipstein-Grobusch, K

2015-06-01

The objectives of the article is to compare pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin (β-hCG) concentrations in dried blood spots (DBSs) with serum of samples obtained from a public hospital in a low-resource setting and to evaluate their stability. Serum and DBS samples were obtained by venipuncture and finger prick from 50 pregnant participants in a cohort study in a public hospital in Accra, Ghana. PAPP-A and β-hCG concentrations from serum and DBS were measured with an AutoDELFIA® (PerkinElmer, PerkinElmer, Turku, Finland) automatic immunoassay. Correlation and Passing-Bablok regression analyses were performed to compare marker levels. High correlation (>0.9) was observed for PAPP-A and β-hCG levels between various sampling techniques. The β-hCG concentration was stable between DBS and serum, PAPP-A concentration consistently lower in DBS. Our findings suggest that β-hCG can be reliably collected from DBS in low-resource tropical settings. The exact conditions of the clinical workflow necessary for reliable PAPP-A measurement in these settings need to be further developed in the future. These findings could have implications for prenatal screening programs feasibility in low-income and middle-income countries, as DBS provides an alternative minimally invasive sampling method, with advantages in sampling technique, stability, logistics, and potential application in low-resource settings. © 2015 John Wiley & Sons, Ltd.

Comparison of imaging modalities and source-localization algorithms in locating the induced activity during deep brain stimulation of the STN.

PubMed

Mideksa, K G; Singh, A; Hoogenboom, N; Hellriegel, H; Krause, H; Schnitzler, A; Deuschl, G; Raethjen, J; Schmidt, G; Muthuraman, M

2016-08-01

One of the most commonly used therapy to treat patients with Parkinson's disease (PD) is deep brain stimulation (DBS) of the subthalamic nucleus (STN). Identifying the most optimal target area for the placement of the DBS electrodes have become one of the intensive research area. In this study, the first aim is to investigate the capabilities of different source-analysis techniques in detecting deep sources located at the sub-cortical level and validating it using the a-priori information about the location of the source, that is, the STN. Secondly, we aim at an investigation of whether EEG or MEG is best suited in mapping the DBS-induced brain activity. To do this, simultaneous EEG and MEG measurement were used to record the DBS-induced electromagnetic potentials and fields. The boundary-element method (BEM) have been used to solve the forward problem. The position of the DBS electrodes was then estimated using the dipole (moving, rotating, and fixed MUSIC), and current-density-reconstruction (CDR) (minimum-norm and sLORETA) approaches. The source-localization results from the dipole approaches demonstrated that the fixed MUSIC algorithm best localizes deep focal sources, whereas the moving dipole detects not only the region of interest but also neighboring regions that are affected by stimulating the STN. The results from the CDR approaches validated the capability of sLORETA in detecting the STN compared to minimum-norm. Moreover, the source-localization results using the EEG modality outperformed that of the MEG by locating the DBS-induced activity in the STN.

Ventral pallidum deep brain stimulation attenuates acute partial, generalized and tonic-clonic seizures in two rat models.

PubMed

Mahoney, Emily C; Zeng, Andrew; Yu, Wilson; Rowe, Mackenzie; Sahai, Siddhartha; Feustel, Paul J; Ramirez-Zamora, Adolfo; Pilitsis, Julie G; Shin, Damian S

2018-05-01

Approximately 30% of individuals with epilepsy are refractory to antiepileptic drugs and currently approved neuromodulatory approaches fall short of providing seizure freedom for many individuals with limited utility for generalized seizures. Here, we expand on previous findings and investigate whether ventral pallidum deep brain stimulation (VP-DBS) can be efficacious for various acute seizure phenotypes. For rats administered pilocarpine, we found that VP-DBS (50 Hz) decreased generalized stage 4/5 seizure median frequency from 9 to 6 and total duration from 1667 to 264 s even after generalized seizures emerged. The transition to brainstem seizures was prevented in almost all animals. VP-DBS immediately after rats exhibited their first partial forebrain stage 3 seizure did not affect the frequency of partial seizures but reduced median partial seizure duration from 271 to 54 s. Stimulation after partial seizures also reduced the occurrence and duration of secondarily generalized stage 4/5 seizures. VP-DBS prior to pilocarpine administration prevented the appearance of partial seizures in almost all animals. Lastly, VP-DBS delayed the onset of generalized tonic-clonic seizures (GTCSs) from 111 to 823 s in rats administered another chemoconvulsant, pentylenetetrazol (PTZ, 90 mg/kg). In this particular rat seizure model, stimulating electrodes placed more laterally in both VP hemispheres and more posterior in the left VP hemisphere provided greatest efficacy for GTCSs. In conclusion, our findings posit that VP-DBS can serve as an effective novel neuromodulatory approach for a variety of acute seizure phenotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Cost-Effectiveness of Deep Brain Stimulation for Advanced Parkinson's Disease in the United States.

PubMed

Pietzsch, Jan B; Garner, Abigail M; Marks, William J

2016-10-01

Deep brain stimulation (DBS), which uses an implantable device to modulate brain activity, is clinically superior to medical therapy for treating advanced Parkinson's disease (PD). We studied the cost-effectiveness of DBS in conjunction with medical therapy compared to best medical therapy (BMT) alone, using the latest clinical and cost data for the U.S. healthcare system. We used a decision-analytic state-transition (Markov) model to project PD progression and associated costs for the two treatment strategies. We estimated the discounted incremental cost-effectiveness ratio (ICER) in U.S. dollars per quality-adjusted life-year (QALY) from the Medicare payer perspective, considering a ten-year horizon, and evaluated the robustness of our projections through extensive deterministic sensitivity analyses. Over ten years, DBS treatment led to discounted total costs of $130,510 compared to $91,026 for BMT and added 1.69 QALYs more than BMT, resulting in an ICER of $23,404 per QALY. This ICER was relatively insensitive to variations in input parameters, with neurostimulator replacement, costs for DBS implantation, and costs for treatment of disease-related falls having the greatest effects. Across all investigated scenarios, including a five-year horizon, ICERs remained under $50,000 per QALY. Longer follow-up periods and younger treatment age were associated with greater cost-effectiveness. DBS is a cost-effective treatment strategy for advanced PD in the U.S. healthcare system across a wide range of assumptions. DBS yields substantial improvements in health-related quality of life at a value profile that compares favorably to other well-accepted therapies. © 2016 International Neuromodulation Society.

Dried blood spot analysis of creatinine with LC-MS/MS in addition to immunosuppressants analysis.

PubMed

Koster, Remco A; Greijdanus, Ben; Alffenaar, Jan-Willem C; Touw, Daan J

2015-02-01

In order to monitor creatinine levels or to adjust the dosage of renally excreted or nephrotoxic drugs, the analysis of creatinine in dried blood spots (DBS) could be a useful addition to DBS analysis. We developed a LC-MS/MS method for the analysis of creatinine in the same DBS extract that was used for the analysis of tacrolimus, sirolimus, everolimus, and cyclosporine A in transplant patients with the use of Whatman FTA DMPK-C cards. The method was validated using three different strategies: a seven-point calibration curve using the intercept of the calibration to correct for the natural presence of creatinine in reference samples, a one-point calibration curve at an extremely high concentration in order to diminish the contribution of the natural presence of creatinine, and the use of creatinine-[(2)H3] with an eight-point calibration curve. The validated range for creatinine was 120 to 480 μmol/L (seven-point calibration curve), 116 to 7000 μmol/L (1-point calibration curve), and 1.00 to 400.0 μmol/L for creatinine-[(2)H3] (eight-point calibration curve). The precision and accuracy results for all three validations showed a maximum CV of 14.0% and a maximum bias of -5.9%. Creatinine in DBS was found stable at ambient temperature and 32 °C for 1 week and at -20 °C for 29 weeks. Good correlations were observed between patient DBS samples and routine enzymatic plasma analysis and showed the capability of the DBS method to be used as an alternative for creatinine plasma measurement.

Influence of subthalamic deep-brain stimulation on cognitive action control in incentive context.

PubMed

Houvenaghel, Jean-François; Duprez, Joan; Argaud, Soizic; Naudet, Florian; Dondaine, Thibaut; Robert, Gabriel Hadrien; Drapier, Sophie; Haegelen, Claire; Jannin, Pierre; Drapier, Dominique; Vérin, Marc; Sauleau, Paul

2016-10-01

Subthalamic nucleus deep-brain stimulation (STN-DBS) is an effective treatment in Parkinson's disease (PD), but can have cognitive side effects, such as increasing the difficulty of producing appropriate responses when a habitual but inappropriate responses represent strong alternatives. STN-DBS also appears to modulate representations of incentives such as monetary rewards. Furthermore, conflict resolution can be modulated by incentive context. We therefore used a rewarded Simon Task to assess the influence of promised rewards on cognitive action control in 50 patients with PD, half of whom were being treated with STN-DBS. Results were analyzed according to the activation-suppression model. We showed that STN-DBS (i) favored the expression of motor impulsivity, as measured with the Barratt Impulsiveness Scale, (ii) facilitated the expression of incentive actions as observed with a greater increase in speed according to promised reward in patients with versus without DBS and (iii) may increase impulsive action selection in an incentive context. In addition, analysis of subgroups of implanted patients suggested that those who exhibited the most impulsive action selection had the least severe disease. This may indicate that patients with less marked disease are more at risk of developing impulsivity postoperatively. Finally, in these patients, incentive context increased the difficulty of resolving conflict situations. As a whole, the current study revealed that in patients with PD, STN-DBS affects the cognitive processes involved in conflict resolution, reward processing and the influence of promised rewards on conflict resolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease

PubMed Central

Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.

2018-01-01

Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141

Autonomy in Depressive Patients Undergoing DBS-Treatment: Informed Consent, Freedom of Will and DBS' Potential to Restore It.

PubMed

Beeker, Timo; Schlaepfer, Thomas E; Coenen, Volker A

2017-01-01

According to the World Health Organization, depression is one of the most common and most disabling psychiatric disorders, affecting at any given time approximately 325 million people worldwide. As there is strong evidence that depressive disorders are associated with a dynamic dysregulation of neural circuits involved in emotional processing, recently several attempts have been made to intervene directly in these circuits via deep brain stimulation (DBS) in patients with treatment-resistant major depressive disorder (MDD). Given the promising results of most of these studies, the rising medical interest in this new treatment correlates with a growing sensitivity to ethical questions. One of the most crucial concerns is that DBS might interfere with patients' ability to make autonomous decisions. Thus, the goal of this article is to evaluate the impact DBS presumably has on the capacity to decide and act autonomously in patients with MDD in the light of the autonomy-undermining effects depression has itself. Following the chronological order of the procedure, special attention will first be paid to depression's effects on patients' capacity to make use of their free will in giving valid Informed Consent. We suggest that while the majority of patients with MDD appear capable of autonomous choices, as it is required for Informed Consent, they might still be unable to effectively act according to their own will whenever acting includes significant personal effort. In reducing disabling depressive symptoms like anhedonia and decrease of energy, DBS for treatment resistant MDD thus rather seems to be an opportunity to substantially increase autonomy than a threat to it.

Measurements of RF Heating during 3.0T MRI of a Pig Implanted with Deep Brain Stimulator

PubMed Central

Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

2012-01-01

Purpose To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. Materials and Methods DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 W/kg and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5T and, at both field strengths, in a phantom. Results At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in-vivo heating differed from those obtained in the phantom. Conclusion The 3.0T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46°C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0T MRI in patients with DBS. PMID:23228310

Innovative approaches to vitamin A assessment.

PubMed

Craft, N E

2001-05-01

The health and sight of millions of children are compromised each year as a consequence of vitamin A (VA) deficiency. Serum retinol is the most commonly used indicator of VA status. Unfortunately, its use is impractical for national surveys because it involves collection of venous blood, centrifugation and frozen storage before analysis. To make VA assessment more practical, we have developed approaches incorporating dried blood spots (DBS) or portable instrumentation. DBS have been used as a sample matrix to screen neonates for many biochemical compounds. Until recently, it was not thought that VA was stable in DBS. However, we demonstrated that the measure of DBS retinol correlates well with serum retinol in both healthy adults (r(2) = 0.88-0.90) and compromised populations (r(2) = 0.73-0.84). Compared with serum retinol, the sensitivity and specificity of detecting VA deficiency by DBS retinol range from 73 to 93% and from 90 to 100%, respectively. Although few data are available, retinol binding protein (RBP) can also be measured in DBS. RBP has been used as a surrogate marker for serum retinol. Correlations coefficients (r(2)) between serum RBP and serum retinol range from 0.4 to 0.8. In addition, work has been done to develop portable instrumentation to measure VA status in the field. A fluorometer has been optimized for VA fluorescence and is linear into the deficient range for the direct fluorimetric measurement of serum holo-RBP. Progress is being made to use the instrument to directly measure holo-RBP in a drop of whole blood.

Evaluation of blood collection filter papers for HIV-1 DNA PCR.

PubMed

Masciotra, Silvina; Khamadi, Samoel; Bilé, Ebi; Puren, Adrian; Fonjungo, Peter; Nguyen, Shon; Girma, Mulu; Downing, Robert; Ramos, Artur; Subbarao, Shambavi; Ellenberger, Dennis

2012-10-01

The collection of dried blood spots (DBS) on Whatman 903 cards has facilitated for years the detection of HIV-1 in infants by DNA PCR as early as 4-6 weeks after birth in resource-limited settings (RLS), but alternate blood collection devices are proving to be necessary. The qualitative detection of HIV-1 DNA by PCR from DBS prepared on three commercially available blood collection cards was evaluated at the Centers for Disease Control and Prevention (CDC) and in four laboratories in Africa. DBS were prepared on Ahlstrom grade 226, Munktell TFN and Whatman 903, and stored under a variety of conditions. DBS were stored at ambient temperature (RT), 37°C with high humidity, and -20°C for varying lengths of time. The presence of HIV-1 DNA was tested using Roche Amplicor HIV-1 DNA (v 1.5) weekly for 4 weeks and at weeks 8 and 12 (RT and 37°C), at weeks 4, 8, and 18 (-20°C) of storage. DBS specimens were also tested after international shipment at RT. In addition, after nearly 3 years storage at -20°C, DBS were also evaluated independently using the COBAS Ampliprep/TaqMan HIV-1 Qual and Abbott RealTime HIV-1 Qualitative tests. HIV-1 DNA was detected equally well on the three blood collection cards regardless of storage conditions and PCR assay. Ahlstrom 226 and Munktell TFN papers were comparable to Whatman 903 for HIV-1 DNA detection and may be considered as optional blood collection devices in resource-limited countries. Published by Elsevier B.V.

Molecular Detection of Streptococcus pneumoniae on Dried Blood Spots from Febrile Nigerian Children Compared to Culture

PubMed Central

Iroh Tam, Pui-Ying; Hernandez-Alvarado, Nelmary; Schleiss, Mark R.; Hassan-Hanga, Fatimah; Onuchukwu, Chuma; Umoru, Dominic; Obaro, Stephen K.

2016-01-01

Background Nigeria has one of the highest burdens of pneumococcal disease in the world, but accurate surveillance is lacking. Molecular detection of infectious pathogens in dried blood spots (DBS) is an ideal method for surveillance of infections in resource-limited settings because of its low cost, minimal blood volumes involved, and ease of storage at ambient temperature. Our study aim was to evaluate a Streptococcus pneumoniae real-time polymerase chain reaction (rt-PCR) assay on DBS from febrile Nigerian children on Whatman 903 and FTA filter papers, compared to the gold standard of culture. Methods Between September 2011 to May 2015, blood was collected from children 5 years of age or under who presented to six hospital study sites throughout northern and central Nigeria with febrile illness, and inoculated into blood culture bottles or spotted onto Whatman 903 or FTA filter paper. Culture and rt-PCR were performed on all samples. Results A total of 537 DBS specimens from 535 children were included in the study, of which 15 were culture-positive for S. pneumoniae. The rt-PCR assay detected S. pneumoniae in 12 DBS specimens (2.2%). One positive rt-PCR result was identified in a culture-negative specimen from a high-risk subject, and two positive rt-PCR results were negative on repeat testing. Six culture-confirmed cases of S. pneumoniae bacteremia were missed. Compared to culture, the overall sensitivities of Whatman 903 and FTA DBS for detection of S. pneumoniae were 57.1% (95% CI 18.4–90.1%) and 62.5% (95% CI 24.5–91.5%), respectively. Nonspecific amplification was noted in an additional 22 DBS (4.1%). Among these, six were positive for a non-S. pneumoniae pathogen on culture. Conclusions Rt-PCR was able to detect S. pneumoniae from clinical DBS specimens, including from a culture-negative specimen. Our findings show promise of this approach as a surveillance diagnostic, but also raise important cautionary questions. Several DBS specimens were detected as S. pneumoniae by rt-PCR despite growth of a non-S. pneumoniae pathogen on culture. A precise definition of what constitutes a positive result is required to avoid falsely over-identifying specimens. PMID:27007889

The use of mass spectrometry to analyze dried blood spots.

PubMed

Wagner, Michel; Tonoli, David; Varesio, Emmanuel; Hopfgartner, Gérard

2016-01-01

Dried blood spots (DBS) typically consist in the deposition of small volumes of capillary blood onto dedicated paper cards. Comparatively to whole blood or plasma samples, their benefits rely in the fact that sample collection is easier and that logistic aspects related to sample storage and shipment can be relatively limited, respectively, without the need of a refrigerator or dry ice. Originally, this approach has been developed in the sixties to support the analysis of phenylalanine for the detection of phenylketonuria in newborns using bacterial inhibition test. In the nineties tandem mass spectrometry was established as the detection technique for phenylalanine and tyrosine. DBS became rapidly recognized for their clinical value: they were widely implemented in pediatric settings with mass spectrometric detection, and were closely associated to the debut of newborn screening (NBS) programs, as a part of public health policies. Since then, sample collection on paper cards has been explored with various analytical techniques in other areas more or less successfully regarding large-scale applications. Moreover, in the last 5 years a regain of interest for DBS was observed and originated from the bioanalytical community to support drug development (e.g., PK studies) or therapeutic drug monitoring mainly. Those recent applications were essentially driven by improved sensitivity of triple quadrupole mass spectrometers. This review presents an overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques. A general introduction to DBS will describe their advantages and historical aspects of their emergence. A second section will focus on blood collection, with a strong emphasis on specific parameters that can impact quantitative analysis, including chromatographic effects, hematocrit effects, blood effects, and analyte stability. A third part of the review is dedicated to sample preparation and will consider off-line and on-line extractions; in particular, instrumental designs that have been developed so far for DBS extraction will be detailed. Flow injection analysis and applications will be discussed in section IV. The application of surface analysis mass spectrometry (DESI, paper spray, DART, APTDCI, MALDI, LDTD-APCI, and ICP) to DBS is described in section V, while applications based on separation techniques (e.g., liquid or gas chromatography) are presented in section VI. To conclude this review, the current status of DBS analysis is summarized, and future perspectives are provided. © 2014 Wiley Periodicals, Inc.

Additional psychometric data for the Spanish Modified Dental Anxiety Scale, and psychometric data for a Spanish version of the Revised Dental Beliefs Survey.

PubMed

Coolidge, Trilby; Hillstead, M Blake; Farjo, Nadia; Weinstein, Philip; Coldwell, Susan E

2010-05-13

Hispanics comprise the largest ethnic minority group in the United States. Previous work with the Spanish Modified Dental Anxiety Scale (MDAS) yielded good validity, but lower test-retest reliability. We report the performance of the Spanish MDAS in a new sample, as well as the performance of the Spanish Revised Dental Beliefs Survey (R-DBS). One hundred sixty two Spanish-speaking adults attending Spanish-language church services or an Hispanic cultural festival completed questionnaires containing the Spanish MDAS, Spanish R-DBS, and dental attendance questions, and underwent a brief oral examination. Church attendees completed the questionnaire a second time, for test-retest purposes. The Spanish MDAS and R-DBS were completed by 156 and 136 adults, respectively. The test-retest reliability of the Spanish MDAS was 0.83 (95% CI = 0.60-0.92). The internal reliability of the Spanish R-DBS was 0.96 (95% CI = 0.94-0.97), and the test-retest reliability was 0.86 (95% CI = 0.64-0.94). The two measures were significantly correlated (Spearman's rho = 0.38, p < 0.001). Participants who do not currently go to a dentist had significantly higher MDAS scores (t = 3.40, df = 106, p = 0.003) as well as significantly higher R-DBS scores (t = 2.21, df = 131, p = 0.029). Participants whose most recent dental visit was for pain or a problem, rather than for a check-up, scored significantly higher on both the MDAS (t = 3.00, df = 106, p = 0.003) and the R-DBS (t = 2.85, df = 92, p = 0.005). Those with high dental fear (MDAS score 19 or greater) were significantly more likely to have severe caries (Chi square = 6.644, df = 2, p = 0.036). Higher scores on the R-DBS were significantly related to having more missing teeth (Spearman's rho = 0.23, p = 0.009). In this sample, the test-retest reliability of the Spanish MDAS was higher. The significant relationships between dental attendance and questionnaire scores, as well as the difference in caries severity seen in those with high fear, add to the evidence of this scale's construct validity in Hispanic samples. Our results also provide evidence for the internal and test-retest reliabilities, as well as the construct validity, of the Spanish R-DBS.

A novel method for extracting nucleic acids from dried blood spots for ultrasensitive detection of low-density Plasmodium falciparum and Plasmodium vivax infections.

PubMed

Zainabadi, Kayvan; Adams, Matthew; Han, Zay Yar; Lwin, Hnin Wai; Han, Kay Thwe; Ouattara, Amed; Thura, Si; Plowe, Christopher V; Nyunt, Myaing M

2017-09-18

Greater Mekong Subregion countries are committed to eliminating Plasmodium falciparum malaria by 2025. Current elimination interventions target infections at parasite densities that can be detected by standard microscopy or rapid diagnostic tests (RDTs). More sensitive detection methods have been developed to detect lower density "asymptomatic" infections that may represent an important transmission reservoir. These ultrasensitive polymerase chain reaction (usPCR) tests have been used to identify target populations for mass drug administration (MDA). To date, malaria usPCR tests have used either venous or capillary blood sampling, which entails complex sample collection, processing and shipping requirements. An ultrasensitive method performed on standard dried blood spots (DBS) would greatly facilitate the molecular surveillance studies needed for targeting elimination interventions. A highly sensitive method for detecting Plasmodium falciparum and P. vivax 18S ribosomal RNA from DBS was developed by empirically optimizing nucleic acid extraction conditions. The limit of detection (LoD) was determined using spiked DBS samples that were dried and stored under simulated field conditions. Further, to assess its utility for routine molecular surveillance, two cross-sectional surveys were performed in Myanmar during the wet and dry seasons. The lower LoD of the DBS-based ultrasensitive assay was 20 parasites/mL for DBS collected on Whatman 3MM filter paper and 23 parasites/mL for Whatman 903 Protein Saver cards-equivalent to 1 parasite per 50 µL DBS. This is about 5000-fold more sensitive than standard RDTs and similar to the LoD of ≤16-22 parasites/mL reported for other ultrasensitive methods based on whole blood. In two cross-sectional surveys in Myanmar, nearly identical prevalence estimates were obtained from contemporaneous DBS samples and capillary blood samples collected during the wet and dry season. The DBS-based ultrasensitive method described in this study shows equal sensitivity as previously described methods based on whole blood, both in its limit of detection and prevalence estimates in two field surveys. The reduced cost and complexity of this method will allow for the scale-up of surveillance studies to target MDA and other malaria elimination interventions, and help lead to a better understanding of the epidemiology of low-density malaria infections.

Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.

PubMed

Gunduz, Aysegul; Morita, Hokuto; Rossi, P Justin; Allen, William L; Alterman, Ron L; Bronte-Stewart, Helen; Butson, Christopher R; Charles, David; Deckers, Sjaak; de Hemptinne, Coralie; DeLong, Mahlon; Dougherty, Darin; Ellrich, Jens; Foote, Kelly D; Giordano, James; Goodman, Wayne; Greenberg, Benjamin D; Greene, David; Gross, Robert; Judy, Jack W; Karst, Edward; Kent, Alexander; Kopell, Brian; Lang, Anthony; Lozano, Andres; Lungu, Codrin; Lyons, Kelly E; Machado, Andre; Martens, Hubert; McIntyre, Cameron; Min, Hoon-Ki; Neimat, Joseph; Ostrem, Jill; Pannu, Sat; Ponce, Francisco; Pouratian, Nader; Reymers, Donnie; Schrock, Lauren; Sheth, Sameer; Shih, Ludy; Stanslaski, Scott; Steinke, G Karl; Stypulkowski, Paul; Tröster, Alexander I; Verhagen, Leo; Walker, Harrison; Okun, Michael S

2015-01-01

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline

PubMed Central

Gunduz, Aysegul; Morita, Hokuto; Rossi, P. Justin; Allen, William L.; Alterman, Ron L.; Bronte-Stewart, Helen; Butson, Christopher R.; Charles, David; Deckers, Sjaak; de Hemptinne, Coralie; DeLong, Mahlon; Dougherty, Darin; Ellrich, Jens; Foote, Kelly D.; Giordano, James; Goodman, Wayne; Greenberg, Benjamin D.; Greene, David; Gross, Robert; Judy, Jack W.; Karst, Edward; Kent, Alexander; Kopell, Brian; Lang, Anthony; Lozano, Andres; Lungu, Codrin; Lyons, Kelly E.; Machado, Andre; Martens, Hubert; McIntyre, Cameron; Min, Hoon-Ki; Neimat, Joseph; Ostrem, Jill; Pannu, Sat; Ponce, Francisco; Pouratian, Nader; Reymers, Donnie; Schrock, Lauren; Sheth, Sameer; Shih, Ludy; Stanslaski, Scott; Steinke, G. Karl; Stypulkowski, Paul; Tröster, Alexander I.; Verhagen, Leo; Walker, Harrison; Okun, Michael S.

2015-01-01

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies. PMID:25526555

[Blood sampling using "dried blood spot": a clinical biology revolution underway?].

PubMed

Hirtz, Christophe; Lehmann, Sylvain

2015-01-01

Blood testing using the dried blood spot (DBS) is used since the 1960s in clinical analysis, mainly within the framework of the neonatal screening (Guthrie test). Since then numerous analytes such as nucleic acids, small molecules or lipids, were successfully measured on the DBS. While this pre-analytical method represents an interesting alternative to classic blood sampling, its use in routine is still limited. We review here the different clinical applications of the blood sampling on DBS and estimate its future place, supported by the new methods of analysis as the LC-MS mass spectrometry.

Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy.

PubMed

Klinger, Neil V; Mittal, Sandeep

2016-01-01

Epilepsy affects 50 million people worldwide and about 30% of these patients will not be adequately controlled with antiepileptic drugs (AEDs) alone. For patients where resective surgery is not indicated, deep brain stimulation (DBS) may be an effective alternative. The majority of available literature targets the thalamic nuclei (anterior; centromedian), subthalamic nucleus, hippocampus, and cerebellum. Here, we review patient outcomes and adverse events related to DBS to these various targets. Data show DBS may be a safe and effective treatment option for refractory epilepsy. Copyright © 2015. Published by Elsevier B.V.

Proceedings of the second annual deep brain stimulation think tank: What's in the pipeline

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunduz, Aysegul; Morita, Hokuto; Rossi, P. Justin

Here the proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Proceedings of the second annual deep brain stimulation think tank: What's in the pipeline

DOE PAGES

Gunduz, Aysegul; Morita, Hokuto; Rossi, P. Justin; ...

2015-05-25

Here the proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

PubMed

Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

2014-01-01

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

Role of deep brain stimulation in modulating memory formation and recall

PubMed Central

Hu, Rollin; Eskandar, Emad; Williams, Ziv

2010-01-01

Deep brain stimulation (DBS) has become an increasingly popular tool for treating a variety of medically refractory neurological and psychiatric disorders such as Parkinson disease, essential tremor, depression, and obsessive-compulsive disorder. Several targets have been identified for ablation or stimulation based on their anatomical location and presumed function. Areas such as the subthalamic nucleus, globus pallidus, and thalamus, for example, are believed to play a key role in motor control and execution, and they are commonly used in the treatment of motor disorders. Limbic structures such as the cingulate cortex and ventral striatum, believed to be important in motivation, emotion, and higher cognition, have also been targeted for treatment of a number of psychiatric disorders. In all of these settings, DBS is largely aimed at addressing the deleterious aspects of these diseases. In Parkinson disease, for example, DBS has been used to reduce rigidity and tremor, whereas in obsessive-compulsive disorder it has been used to limit compulsive behavior. More recently, however, attention has also turned to the potential use of DBS for enhancing or improving otherwise nonpathological aspects of cognitive function. This review explores the potential role of DBS in augmenting memory formation and recall, and the authors discuss recent studies and future trends in this emerging field. PMID:19569891

Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

PubMed Central

Jeong, Da Un; Lee, Ji Eun; Lee, Sung Eun; Chang, Won Seok; Kim, Sung June; Chang, Jin Woo

2014-01-01

Deep brain stimulation (DBS) has been found to have therapeutic effects in patients with dementia, but DBS mechanisms remain elusive. To provide evidence for the effectiveness of DBS as a treatment for dementia, we performed DBS in a rat model of dementia with intracerebroventricular administration of 192 IgG-saporins. We utilized four groups of rats, group 1, unlesioned control; group 2, cholinergic lesion; group 3, cholinergic lesion plus medial septum (MS) electrode implantation (sham stimulation); group 4, cholinergic lesions plus MS electrode implantation and stimulation. During the probe test in the water maze, performance of the lesion group decreased for measures of time spent and the number of swim crossings over the previous platform location. Interestingly, the stimulation group showed an equivalent performance to the normal group on all measures. And these are partially reversed by the electrode implantation. Acetylcholinesterase activity in the hippocampus was decreased in lesion and implantation groups, whereas activity in the stimulation group was not different from the normal group. Hippocampal neurogenesis was increased in the stimulation group. Our results revealed that DBS of MS restores spatial memory after damage to cholinergic neurons. This effect is associated with an increase in hippocampal cholinergic activity and neurogenesis. PMID:25101288

The Driving Behavior Survey as a Measure of Behavioral Stress Responses to MVA-related PTSD

PubMed Central

Baker, Aaron S.; Litwack, Scott D.; Clapp, Joshua D.; Beck, J. Gayle; Sloan, Denise M.

2014-01-01

Numerous treatments are available that address the core symptoms of posttraumatic stress disorder (PTSD). However, there are a number of related behavioral stress responses that are not assessed with PTSD measures, yet these behavioral stress responses affect quality of life. The goal of the current study was to investigate whether a recently developed measure of behavioral stress response, the Driving Behavior Survey (DBS), was sensitive to change associated with treatment among a group of participants diagnosed with PTSD. The DBS indexes anxious driving behavior, which is frequently observed among individuals with motor vehicle accident-related PTSD. Participants (n = 40) were racially-diverse adults (M age =40.78, 63% women) who met diagnostic criteria for motor vehicle accident-related PTSD. Hierarchical linear modeling analyses indicated that participants who were assigned to a brief, exposure-based intervention displayed significant reductions on the DBS subscales relative to participants assigned to the waitlist control condition (r = .41-.43). Moreover, meditational analyses indicated that the observed reductions on the DBS subscales were not better accounted for by reductions in PTSD. Taken together, these findings suggest that the DBS subscales are sensitive to changes associated with PTSD treatment and can be used to augment outcome measures in PTSD treatment trials PMID:24491201

The Driving Behavior Survey as a Measure of Behavioral Stress Responses to MVA-Related PTSD

PubMed Central

Baker, Aaron S.; Litwack, Scott D.; Clapp, Joshua D.; Beck, J. Gayle; Sloan, Denise M.

2014-01-01

Numerous treatments are available that address the core symptoms of posttraumatic stress disorder (PTSD). However, there are a number of related behavioral stress responses that are not assessed with PTSD measures, yet these behavioral stress responses affect quality of life. The goal of the current study was to investigate whether a recently developed measure of behavioral stress response, the Driving Behavior Survey (DBS), was sensitive to change associated with treatment among a group of participants diagnosed with PTSD. The DBS indexes anxious driving behavior, which is frequently observed among individuals with motor vehicle accident-related PTSD. Participants (n = 40) were racially diverse adults (M age = 40.78, 63% women) who met diagnostic criteria for motor vehicle accident-related PTSD. Hierarchical linear modeling analyses indicated that participants who were assigned to a brief, exposure-based intervention displayed significant reductions on the DBS subscales relative to participants assigned to the wait-list control condition (r = .41–.43). Moreover, mediational analyses indicated that the observed reductions on the DBS subscales were not better accounted for by reductions in PTSD. Taken together, these findings suggest that the DBS subscales are sensitive to changes associated with PTSD treatment and can be used to augment outcome assessment in PTSD treatment trials. PMID:24800313

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.

PubMed

Widge, Alik S; Malone, Donald A; Dougherty, Darin D

2018-01-01

Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

Intraoperative MR-guided DBS implantation for treating PD and ET

NASA Astrophysics Data System (ADS)

Liu, Haiying; Maxwell, Robert E.; Truwit, Charles L.

2001-05-01

Deep brain stimulator (DBS) implantation is a promising treatment alternative for suppressing the motor tremor symptoms in Parkinson disease (PD) patient. The main objective is to develop a minimally invasive approach using high spatial resolution and soft-tissue contrast MR imaging techniques to guide the surgical placement of DBS. In the MR-guided procedure, the high spatial resolution MR images were obtained intra-operatively and used to target stereotactically a specific deep brain location. The neurosurgery for craniotomy was performed in the front of the magnet outside of the 10 Gauss line. Aided with positional registration assembly for the stereotactic head frame, the target location (VIM or GPi or STN) in deep brain areas was identified and measured from the MR images in reference to the markers in the calibration assembly of the head frame before the burrhole prep. In 20 patients, MR- guided DBS implantations have been performed according to the new methodology. MR-guided DBS implantation at high magnetic field strength has been shown to be feasible and desirable. In addition to the improved outcome, this offers a new surgical approach in which intra-operative visualization is possible during intervention, and any complications such as bleeding can be assessed in situ immediately prior to dural closure.

Temperature Control at DBS Electrodes using Heat Sink: Experimentally Validated FEM Model of DBS lead Architecture

PubMed Central

Elwassif, Maged M.; Datta, Abhishek; Rahman, Asif; Bikson, Marom

2012-01-01

There is a growing interest in the use of Deep Brain Stimulation for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. MRI) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols, and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: 1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); 2) does not interfere with device efficacy; and 3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure. PMID:22764359

Aspects of oral communication in patients with Parkinson's disease submitted to Deep Brain Stimulation.

PubMed

Cruz, Aline Nunes da; Beber, Bárbara Costa; Olchik, Maira Rozenfeld; Chaves, Márcia Lorena Fagundes; Rieder, Carlos Roberto de Mello; Dornelles, Sílvia

2016-01-01

Deep Brain Stimulation (DBS) has been satisfactorily used to control the cardinal motor symptoms of Parkinson's disease (PD), but little is known about its impact on communication. This study aimed to characterize the aspects of cognition, language, speech, voice, and self-perception in two patients with PD, pre- and post- DBS implant surgery. The patients were assessed using a cognitive screening test, a brief language evaluation, a self-declared protocol, and an analysis of the aspects of voice and speech, which was conducted by a specialized Speech-language Therapist who was blinded for the study. At the pre-surgery assessment, Case I showed impairment regarding the aspects of cognition, language and voice, whereas Case II showed impairment only with respect to the voice aspect. The post-surgery evaluation of the cases showed an opposite pattern of the effect of DBS after analysis of the communication data: Case I, who presented greater impairment before the surgery, showed improvement in some aspects; Case II, who presented lower communicative impairment before the surgery, showed worsening in other aspects. This study shows that DBS may influence different communication aspects both positively and negatively. Factors associated with the different effects caused by DBS on the communication of patients with PD need to be further investigated.

DEVELOPMENT OF DISRUPTIVE BEHAVIORS IN YOUNG CHILDREN: A PROSPECTIVE POPULATION-BASED COHORT STUDY

PubMed Central

BAILLARGEON, RAYMOND H.; MORISSET, ALEXANDRE; KEENAN, KATE; NORMAND, CLAUDE L.; SÉGUIN, JEAN R.; JAPEL, CHRISTA; CAO, GUANQIONG

2013-01-01

We know relatively little about the development of disruptive behaviors (DBs), and gender differences therein. The objective of this study was to describe the continuity and discontinuity in the degree to which young children in the general population are reported to exhibit specific DBs over time. Data came from the Québec Longitudinal Study of Child Development. First, the results show that relatively few children exhibit DBs on a frequent basis at 41 months of age. Second, the results show that a majority of children who exhibit a particular DB on a frequent basis at 41 months of age did not do so 1 year earlier. In addition, a majority of children who exhibited a particular DB on a frequent basis at 29 months of age no longer do so 1 year later. Third, gender differences in DBs (boys > girls) are either emerging or at least increasing in magnitude between 29 and 41 months of age. Consistent with the canalization of the behavioral development principle, children who exhibited DBs on a frequent basis at 29 months of age are less likely to stop doing so in the following year if they had exhibited the same behaviors at 17 months of age. PMID:28079905

Diffusion Tensor Imaging Based Thalamic Segmentation in Deep Brain Stimulation for Chronic Pain Conditions

PubMed Central

Kim, Won; Chivukula, Srinivas; Hauptman, Jason; Pouratian, Nader

2016-01-01

Background/Aims Thalamic deep brain stimulation (DBS) for the treatment of medically refractory pain has largely been abandoned on account of its inconsistent and oftentimes poor efficacy. Our aim here was to use diffusion tensor imaging (DTI)-based segmentation to assess the internal thalamic nuclei of patients who have undergone thalamic DBS for intractable pain and retrospectively correlate lead position with clinical outcome. Methods DTI-based segmentation was performed on 5 patients who underwent sensory thalamus DBS for chronic pain. Postoperative computed tomography (CT) images obtained for electrode placement were fused with preoperative MRIs that had undergone DTI-based thalamic segmentation. Sensory thalamus maps of 4 patients were analyzed for lead positioning and interpatient variability. Results Four patients who experienced significant pain relief following DBS demonstrated contact positions within the DTI-determined sensory thalamus or in its vicinity, whereas one who did not respond to stimulation did not. Only four voxels (2%) within the sensory thalamus were mutually shared among patients; 108 voxels (58%) were uniquely represented. Conclusions DTI-based segmentation of the thalamus can be used to confirm thalamic lead placement relative to the sensory thalamus, and may serve as a useful tool to guide thalamic DBS electrode implantation in the future. PMID:27537848

Radiofrequency Lesions through Deep Brain Stimulation Electrodes in Movement Disorders: Case Report and Review of the Literature.

PubMed

Pérez-Suárez, Javier; Torres Díaz, Cristina V; López Manzanares, Lydia; Navas García, Marta; Pastor, Jesús; Barrio Fernández, Patricia; G de Sola, Rafael

2017-01-01

Although there are few reports of radiofrequency lesions performed through deep brain stimulation (DBS) electrodes in patients with movement disorders, experience with this method is scarce. We present 2 patients who had been previously treated with DBS of subthalamic nuclei (STN) and the ventral intermediate (VIM) nucleus of the thalamus for Parkinson's disease and essential tremor, respectively, and underwent a radiofrequency lesion through their DBS electrodes after developing a hardware infection. The authors conduct a review of the literature regarding this method. Both patients had a good clinical outcome after 20 and 8 months, respectively, as assessed by a reduction in Fahn-Tolosa-Marin Scale and Unified Parkinson's Disease Rating Scale scores. The second patient underwent a second DBS system implantation surgery after his radiofrequency treatment to optimize his management, achieving optimal clinical control with lower current and drug requirements than before the radiofrequency intervention. No adverse effects were observed. Radiofrequency lesions through DBS electrodes allow the creation of small and localized lesions. Its effectiveness and low-risk profile, in addition to its low cost, make this procedure suitable and a possible alternative in the therapeutic repertoire for the surgical treatment of movement disorders. © 2017 S. Karger AG, Basel.

Deep brain stimulation does not change neurovascular coupling in non-motor visual cortex: an autonomic and visual evoked blood flow velocity response study.

PubMed

Azevedo, Elsa; Santos, Rosa; Freitas, João; Rosas, Maria-José; Gago, Miguel; Garrett, Carolina; Rosengarten, Bernhard

2010-11-01

In Parkinson's disease (PD) subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function. Also an effect on the neurovascular coupling in motor cortex was reported due to a parallel activation of a subthalamic vasodilator area (SVA). To address this issue further we analysed neurovascular coupling in a non-motor area. Twenty PD patients selected for bilateral STN-DBS were investigated with functional transcranial Doppler (f-TCD) before and after surgery. Hemodynamic responses to visual stimulation were registered in left posterior cerebral artery (PCA) and analysed with a control-system approach (parameters gain, rate time, attenuation and natural frequency). To exclude autonomic effects of STN-DBS, we also addressed spectrum analysis of heart rate and of systolic arterial blood pressure variability, and baroreceptor gain. Findings in the PD group were compared with healthy age-matched controls. PD patients showed no neurovascular coupling changes in PCA territory, compared to controls, and STN-DBS changed neither blood flow regulatory parameters nor autonomic function. Improvement of vasoregulation in some motor cortical areas after STN-DBS might be related to an improved neuronal functional rather than indicating an effect on the neurovascular coupling or autonomic function. Copyright © 2010 Elsevier Ltd. All rights reserved.

Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.

PubMed

Russo, Jennifer F; Sheth, Sameer A

2015-06-01

Chronic neuropathic pain is estimated to affect 3%-4.5% of the worldwide population. It is associated with significant loss of productive time, withdrawal from the workforce, development of mood disorders such as depression and anxiety, and disruption of family and social life. Current medical therapeutics often fail to adequately treat chronic neuropathic pain. Deep brain stimulation (DBS) targeting subcortical structures such as the periaqueductal gray, the ventral posterior lateral and medial thalamic nuclei, and the internal capsule has been investigated for the relief of refractory neuropathic pain over the past 3 decades. Recent work has identified the dorsal anterior cingulate cortex (dACC) as a new potential neuromodulation target given its central role in cognitive and affective processing. In this review, the authors briefly discuss the history of DBS for chronic neuropathic pain in the United States and present evidence supporting dACC DBS for this indication. They review existent literature on dACC DBS and summarize important findings from imaging and neurophysiological studies supporting a central role for the dACC in the processing of chronic neuropathic pain. The available neurophysiological and empirical clinical evidence suggests that dACC DBS is a viable therapeutic option for the treatment of chronic neuropathic pain and warrants further investigation.

Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation

PubMed Central

Zhang, Jianyu; Ghosh, Debabrata; McIntyre, Cameron C.; Vitek, Jerrold L.

2012-01-01

Clinical evidence has suggested that subtle changes in deep brain stimulation (DBS) settings can have differential effects on bradykinesia and rigidity in patients with Parkinson's disease. In this study, we first investigated the degree of improvement in bradykinesia and rigidity during targeted globus pallidus DBS in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus macaques. Behavioral outcomes of DBS were then coupled with detailed, subject-specific computational models of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and internal capsule (IC) to determine which neuronal pathways when modulated with high-frequency electrical stimulation best correlate with improvement in motor symptoms. The modeling results support the hypothesis that multiple neuronal pathways can underlie the therapeutic effect of DBS on parkinsonian bradykinesia and rigidity. Across all three subjects, improvements in rigidity correlated most strongly with spread of neuronal activation into IC, driving a small percentage of fibers within this tract (<10% on average). The most robust effect on bradykinesia resulted from stimulating a combination of sensorimotor axonal projections within the GP, specifically at the site of the medial medullary lamina. Thus the beneficial effects of pallidal DBS for parkinsonian symptoms may occur from multiple targets within and near the target nucleus. PMID:22514292

Intraoperative acceleration measurements to quantify improvement in tremor during deep brain stimulation surgery.

PubMed

Shah, Ashesh; Coste, Jérôme; Lemaire, Jean-Jacques; Taub, Ethan; Schüpbach, W M Michael; Pollo, Claudio; Schkommodau, Erik; Guzman, Raphael; Hemm-Ode, Simone

2017-05-01

Deep brain stimulation (DBS) surgery is extensively used in the treatment of movement disorders. Nevertheless, methods to evaluate the clinical response during intraoperative stimulation tests to identify the optimal position for the implantation of the chronic DBS lead remain subjective. In this paper, we describe a new, versatile method for quantitative intraoperative evaluation of improvement in tremor with an acceleration sensor that is mounted on the patient's wrist during surgery. At each anatomical test position, the improvement in tremor compared to the initial tremor is estimated on the basis of extracted outcome measures. This method was tested on 15 tremor patients undergoing DBS surgery in two centers. Data from 359 stimulation tests were acquired. Our results suggest that accelerometric evaluation detects tremor changes more sensitively than subjective visual ratings. The effective stimulation current amplitudes identified from the quantitative data (1.1 ± 0.8 mA) are lower than those identified by visual evaluation (1.7 ± 0.8 mA) for similar improvement in tremor. Additionally, if these data had been used to choose the chronic implant position of the DBS lead, 15 of the 26 choices would have been different. These results show that our method of accelerometric evaluation can potentially improve DBS targeting.

Pilot proficiency testing study for second tier congenital adrenal hyperplasia newborn screening.

PubMed

De Jesús, Víctor R; Simms, David A; Schiffer, Jarad; Kennedy, Meredith; Mei, Joanne V; Hannon, W Harry

2010-11-11

Congenital adrenal hyperplasia (CAH) is caused by inherited defects in steroid biosynthesis. The Newborn Screening Quality Assurance Program (NSQAP) initiated a pilot, dried-blood spot (DBS)-based proficiency testing program designed to investigate materials and laboratory performance for second tier CAH screening by tandem mass spectrometry (MS/MS). The ratio of 17-α-hydroxyprogesterone (17-OHP), androstenedione (4-AD) and cortisol is used as an indicator of CAH in laboratory protocols for second tier analysis of DBS specimens. DBS prepared by NSQAP contained a range of steroid concentrations resulting in different clinical ratios. Laboratories received blind-coded DBS specimens and reported results to NSQAP for evaluation. Quantitative values reported by participants for 17-OHP, 4-AD, and cortisol, reflected small differences in their analytical methods. Average quantitative values for 17-OHP increased from 81% to 107% recovery over the 3.5-year period; cortisol recoveries increased from 61.9% to 89.5%; and 4-AD recoveries decreased from 184% to 68%. Laboratory participation in the CAH second tier proficiency testing program has resulted in improved analyte recoveries and enhanced sample preparation methodologies. NSQAP services for the second tier CAH analysis in DBS demonstrate the need for surveillance to ensure harmonization and continuous improvements, and to achieve sustained high-performance of newborn screening laboratories worldwide. Published by Elsevier B.V.

Reoperation for suboptimal outcomes after deep brain stimulation surgery.

PubMed

Ellis, Tina-Marie; Foote, Kelly D; Fernandez, Hubert H; Sudhyadhom, Atchar; Rodriguez, Ramon L; Zeilman, Pamela; Jacobson, Charles E; Okun, Michael S

2008-10-01

To examine a case series of reoperations for deep brain stimulation (DBS) leads in which clinical scenarios revealed suboptimal outcome from a previous operation. Suboptimally placed DBS leads are one potential reason for unsatisfactory results after surgery for Parkinson's disease (PD), essential tremor (ET), or dystonia. In a previous study of patients who experienced suboptimal results, 19 of 41 patients had misplaced leads. Similarly, another report commented that lead placement beyond a 2- to 3-mm window resulted in inadequate clinical benefit, and, in 1 patient, revision improved outcome. The goal of the current study was to perform an unblinded retrospective chart review of DBS patients with unsatisfactory outcomes who presented for reoperation. Patients who had DBS lead replacements after reoperation were assessed with the use of a retrospective review of an institutional review board-approved movement disorders database. Cases of reoperation for suboptimal clinical benefit were included, and cases of replacement of DBS leads caused by infection or hardware malfunction were excluded. Data points studied included age, disease duration, diagnosis, motor outcomes (the Unified Parkinson Disease Rating Scale III in PD, the Tremor Rating Scale in ET, and the Unified Dystonia Rating Scale in dystonia), quality of life (Parkinson's Disease Questionnaire-39 in PD), and the Clinician Global Impression scale. The data from before and after reoperation were examined to determine the estimated impact of repeat surgery. There were 11 patients with PD, 7 with ET, and 4 with dystonia. The average age of the PD group was 52 years, the disease duration was 10 years, and the average vector distance of the location of the active DBS contact was adjusted 5.5 mm. Six patients (54%) with PD had preoperative off medication on DBS Unified Parkinson Disease Rating Scale scores that could be compared with postoperative off medication on DBS scores. The average improvement across this group of patients was 24.4%. The Parkinson's Disease Questionnaire-39 improved in the areas of mobility (28.18), activities of daily living (14.77), emotion (14.72), stigma (17.61), and discomfort (17.42). The average age of the ET group was 66 years, the disease duration was 29 years, and the average adjusted distance was 6.1 mm. Five ET patients (83.3%) in the cohort had a prereplacement on DBS Tremor Rating Scale and a postreplacement on DBS Tremor Rating Scale with the average improvement of 60.4%. The average age of the dystonia group was 39 years, the average disease duration was 7 years, and the average adjusted lead distance was 6.7 mm. Three patients (75%) with dystonia had prereplacement on DBS Unified Dystonia Rating Scale and postreplacement on DBS Unified Dystonia Rating Scale scores. Across these 3 dystonia patients, the improvement was 12.8%. Clinician Global Impression scale scores (1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse) after replacement revealed the following results in patients with PD: 1, 7 patients; 2, 3 patients; 3, 1 patient); with ET (1, 4 patients; 2, 3 patients); and with dystonia (1, 1 patient; 2, 2 patients; 3, 1 patient). The latency from original lead placement to reoperation (repositioning/revision) overall was 28.9 months (range, 2-104 mo); however, in leads referred from outside institutions (n = 11 patients), this latency was 48 months (range, 12-104 mo) compared with leads implanted by surgeons from the University of Florida (n = 11 patients), which was 9.7 months (range, 2-19 mo). The most common clinical history was failure to achieve a perceived outcome; however, history of an asymmetric benefit was present in 4 (18.2%) of 22 patients, and lead migration was present in 3 (13.6%) of 22 patients. There are many potential causes of suboptimal benefit after DBS. Timely identification of suboptimal lead placements followed by reoperation and repositioning/replacement in a subset of patients may improve outcomes.

Should patients with risk factors be tested for hypersensitivity to contrast media: a prospective study.

PubMed

Tepetam, Fatma Merve; Çiftaslan, Nezihe; Oruç, Özlem; Duman, Dildar; Ağca, Meltem; Bulut, İsmet; Çolakoğlu, Bahattin

2016-08-01

Previous hypersensitivity reactions to contrast media (CM), atopy, atopic disease, drug allergy, and age (20-29 or >55) are risk factors for CM hypersensitivity reactions. Our aim was to evaluate whether these risk factors should prompt skin testing for diagnosing CM allergy. The study was conducted among patients referred for allergy testing with CM. Skin tests were performed with non ionic or gadolinium CM, recommended by a radiologist. After completion of tests patients were telephonically queried on their symptoms of reactions. 151 risk patients (53 men, 98 women; mean age 55.2) were included in the study. Only 13 (9 %) had a history of hypersensitivity reaction to CM. Compared with the other patients, atopy was significantly more common in patients with a history of CM hypersensitivity reactions. Female gender and mean age were also higher, but not significant. All of the tests with CMs were negative. Only one patient reported urticaria within 1-2 min after administration of CM (telephonically). Atopy can increase the risk of CM allergy. However, skin tests with CMs may be inefficient, unnecessary, and time-consuming, except in cases with a history of CM allergy. Premedication protocols appear to be beneficial in patients with a history of CM allergy and cannot be recommended for patients with well-controlled asthma, rhinitis, atopic dermatitis or history of drug allergy.