Snellings, André; Sagher, Oren; Anderson, David J.; Aldridge, J. Wayne
2016-01-01
Object A wavelet-based measure was developed to quantitatively assess neural background activity taken during surgical neurophysiological recordings to localize the boundaries of the subthalamic nucleus during target localization for deep brain stimulator implant surgery. Methods Neural electrophysiological data was recorded from 14 patients (20 tracks, n = 275 individual recording sites) with dopamine-sensitive idiopathic Parkinson’s disease during the target localization portion of deep brain stimulator implant surgery. During intraoperative recording the STN was identified based upon audio and visual monitoring of neural firing patterns, kinesthetic tests, and comparisons between neural behavior and known characteristics of the target nucleus. The quantitative wavelet-based measure was applied off-line using MATLAB software to measure the magnitude of the neural background activity, and the results of this analysis were compared to the intraoperative conclusions. Wavelet-derived estimates were compared to power spectral density measures. Results The wavelet-derived background levels were significantly higher in regions encompassed by the clinically estimated boundaries of the STN than in surrounding regions (STN: 225 ± 61 μV vs. ventral to STN: 112 ± 32 μV, and dorsal to STN: 136 ± 66 μV). In every track, the absolute maximum magnitude was found within the clinically identified STN. The wavelet-derived background levels provided a more consistent index with less variability than power spectral density. Conclusions The wavelet-derived background activity assessor can be calculated quickly, requires no spike sorting, and can be reliably used to identify the STN with very little subjective interpretation required. This method may facilitate rapid intraoperative identification of subthalamic nucleus borders. PMID:19344225
Danish, Shabbar F; Baltuch, Gordon H; Jaggi, Jurg L; Wong, Stephen
2008-04-01
Microelectrode recording during deep brain stimulation surgery is a useful adjunct for subthalamic nucleus (STN) localization. We hypothesize that information in the nonspike background activity can help identify STN boundaries. We present results from a novel quantitative analysis that accomplishes this goal. Thirteen consecutive microelectrode recordings were retrospectively analyzed. Spikes were removed from the recordings with an automated algorithm. The remaining "despiked" signals were converted via root mean square amplitude and curve length calculations into "feature profile" time series. Subthalamic nucleus boundaries determined by inspection, based on sustained deviations from baseline for each feature profile, were compared against those determined intraoperatively by the clinical neurophysiologist. Feature profile activity within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity of STN entry was 60% and 90% for curve length and root mean square amplitude, respectively, when agreement within 0.5 mm of the neurophysiologist's prediction was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm, respectively. Reproducible activity patterns in deep brain stimulation microelectrode recordings can allow accurate identification of STN boundaries. Quantitative analyses of this type may provide useful adjunctive information for electrode placement in deep brain stimulation surgery.
Telford, Ryan; Vattoth, Surjith
2014-01-01
Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832
Tractography patterns of subthalamic nucleus deep brain stimulation.
Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin
2016-04-01
Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical
Innovations in deep brain stimulation methodology.
Kühn, Andrea A; Volkmann, Jens
2017-01-01
Deep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near-term clinical application. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.
Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.
Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S
2018-04-01
Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.
Brain networks modulated by subthalamic nucleus deep brain stimulation.
Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A
2016-09-01
Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The
Deep-brain-stimulation does not impair deglutition in Parkinson's disease.
Lengerer, Sabrina; Kipping, Judy; Rommel, Natalie; Weiss, Daniel; Breit, Sorin; Gasser, Thomas; Plewnia, Christian; Krüger, Rejko; Wächter, Tobias
2012-08-01
A large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e., aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD. Videofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The 'New Zealand index for multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. Preoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency. In Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.
Background rejection in NEXT using deep neural networks
Renner, J.; Farbin, A.; Vidal, J. Muñoz; ...
2017-01-16
Here, we investigate the potential of using deep learning techniques to reject background events in searches for neutrinoless double beta decay with high pressure xenon time projection chambers capable of detailed track reconstruction. The differences in the topological signatures of background and signal events can be learned by deep neural networks via training over many thousands of events. These networks can then be used to classify further events as signal or background, providing an additional background rejection factor at an acceptable loss of efficiency. The networks trained in this study performed better than previous methods developed based on the usemore » of the same topological signatures by a factor of 1.2 to 1.6, and there is potential for further improvement.« less
Snellings, André; Sagher, Oren; Anderson, David J; Aldridge, J Wayne
2009-10-01
The authors developed a wavelet-based measure for quantitative assessment of neural background activity during intraoperative neurophysiological recordings so that the boundaries of the subthalamic nucleus (STN) can be more easily localized for electrode implantation. Neural electrophysiological data were recorded in 14 patients (20 tracks and 275 individual recording sites) with dopamine-sensitive idiopathic Parkinson disease during the target localization portion of deep brain stimulator implantation surgery. During intraoperative recording, the STN was identified based on audio and visual monitoring of neural firing patterns, kinesthetic tests, and comparisons between neural behavior and the known characteristics of the target nucleus. The quantitative wavelet-based measure was applied offline using commercially available software to measure the magnitude of the neural background activity, and the results of this analysis were compared with the intraoperative conclusions. Wavelet-derived estimates were also compared with power spectral density measurements. The wavelet-derived background levels were significantly higher in regions encompassed by the clinically estimated boundaries of the STN than in the surrounding regions (STN, 225 +/- 61 microV; ventral to the STN, 112 +/- 32 microV; and dorsal to the STN, 136 +/- 66 microV). In every track, the absolute maximum magnitude was found within the clinically identified STN. The wavelet-derived background levels provided a more consistent index with less variability than measurements with power spectral density. Wavelet-derived background activity can be calculated quickly, does not require spike sorting, and can be used to identify the STN reliably with very little subjective interpretation required. This method may facilitate the rapid intraoperative identification of STN borders.
2014-01-01
Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669
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.
Brain organization and specialization in deep-sea chondrichthyans.
Yopak, Kara E; Montgomery, John C
2008-01-01
Chondrichthyans occupy a basal place in vertebrate evolution and offer a relatively unexplored opportunity to study the evolution of vertebrate brains. This study examines the brain morphology of 22 species of deep-sea sharks and holocephalans, in relation to both phylogeny and ecology. Both relative brain size (expressed as residuals) and the relative development of the five major brain areas (telencephalon, diencephalon, mesencephalon, cerebellum, and medulla) were assessed. The cerebellar-like structures, which receive projections from the electroreceptive and lateral line organs, were also examined as a discrete part of the medulla. Although the species examined spanned three major chondrichthyan groupings (Squalomorphii, Galeomorphii, Holocephali), brain size and the relative development of the major brain areas did not track phylogenetic groupings. Rather, a hierarchical cluster analysis performed on the deep-sea sharks and holocephalans shows that these species all share the common characteristics of a relatively reduced telencephalon and smooth cerebellar corpus, as well as extreme relative enlargement of the medulla, specifically the cerebellar-like lobes. Although this study was not a functional analysis, it provides evidence that brain variation in deep-sea chondichthyans shows adaptive patterns in addition to underlying phylogenetic patterns, and that particular brain patterns might be interpreted as 'cerebrotypes'. (c) 2008 S. Karger AG, Basel
Laser treatments of deep-seated brain lesions
NASA Astrophysics Data System (ADS)
Ward, Helen A.
1997-06-01
The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.
Analysis of evoked deep brain connectivity.
Klimeš, Petr; Janeček, Jiři; Jurák, Pavel; Halámek, Josef; Chládek, Han; Brázdil, Milan
2013-01-01
Establishing dependencies and connectivity among different structures in the human brain is an extremely complex issue. Methods that are often used for connectivity analysis are based on correlation mechanisms. Correlation methods can analyze changes in signal shape or instantaneous power level. Although recent studies imply that observation of results from both groups of methods together can disclose some of the basic functions and behavior of the human brain during mental activity and decision-making, there is no technique covering changes in the shape of signals along with changes in their power levels. We present a method using a time evaluation of the correlation along with a comparison of power levels in every available contact pair from intracranial electrodes placed in deep brain structures. Observing shape changes in signals after stimulation together with their power levels provides us with new information about signal character between different structures in the brain during task-related events - visual stimulation with motor response. The results for a subject with 95 intracerebral contacts used in this paper demonstrate a clear methodology capable of spatially analyzing connectivity among deep brain structures.
Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.
Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian
2014-10-01
Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. Copyright © 2014 Elsevier Ltd. All rights reserved.
Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.
2012-01-01
Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514
The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.
Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter
2017-04-01
Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could
Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy
Liu, Ning; Cui, Xu; Bryant, Daniel M.; Glover, Gary H.; Reiss, Allan L.
2015-01-01
Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson’s correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research. PMID:25798327
Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.
Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E
2011-06-29
The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.
Deep Learning for Brain MRI Segmentation: State of the Art and Future Directions.
Akkus, Zeynettin; Galimzianova, Alfiia; Hoogi, Assaf; Rubin, Daniel L; Erickson, Bradley J
2017-08-01
Quantitative analysis of brain MRI is routine for many neurological diseases and conditions and relies on accurate segmentation of structures of interest. Deep learning-based segmentation approaches for brain MRI are gaining interest due to their self-learning and generalization ability over large amounts of data. As the deep learning architectures are becoming more mature, they gradually outperform previous state-of-the-art classical machine learning algorithms. This review aims to provide an overview of current deep learning-based segmentation approaches for quantitative brain MRI. First we review the current deep learning architectures used for segmentation of anatomical brain structures and brain lesions. Next, the performance, speed, and properties of deep learning approaches are summarized and discussed. Finally, we provide a critical assessment of the current state and identify likely future developments and trends.
The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s disease
Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M.; Tan, Huiling
2017-01-01
Abstract Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson’s disease, elevations in beta activity (13–35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson’s disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this
Transmission in near-infrared optical windows for deep brain imaging.
Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert
2016-01-01
Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[Long-term care of Parkinson patients with deep brain stimulation].
Allert, N; Barbe, M T; Timmermann, L; Coenen, V A
2011-12-01
For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception. © Georg Thieme Verlag KG Stuttgart · New York.
Deep brain stimulation as a functional scalpel.
Broggi, G; Franzini, A; Tringali, G; Ferroli, P; Marras, C; Romito, L; Maccagnano, E
2006-01-01
Since 1995, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan (INNCB,) 401 deep brain electrodes were implanted to treat several drug-resistant neurological syndromes (Fig. 1). More than 200 patients are still available for follow-up and therapeutical considerations. In this paper our experience is reviewed and pioneered fields are highlighted. The reported series of patients extends the use of deep brain stimulation beyond the field of Parkinson's disease to new fields such as cluster headache, disruptive behaviour, SUNCt, epilepsy and tardive dystonia. The low complication rate, the reversibility of the procedure and the available image guided surgery tools will further increase the therapeutic applications of DBS. New therapeutical applications are expected for this functional scalpel.
Deep learning for brain tumor classification
NASA Astrophysics Data System (ADS)
Paul, Justin S.; Plassard, Andrew J.; Landman, Bennett A.; Fabbri, Daniel
2017-03-01
Recent research has shown that deep learning methods have performed well on supervised machine learning, image classification tasks. The purpose of this study is to apply deep learning methods to classify brain images with different tumor types: meningioma, glioma, and pituitary. A dataset was publicly released containing 3,064 T1-weighted contrast enhanced MRI (CE-MRI) brain images from 233 patients with either meningioma, glioma, or pituitary tumors split across axial, coronal, or sagittal planes. This research focuses on the 989 axial images from 191 patients in order to avoid confusing the neural networks with three different planes containing the same diagnosis. Two types of neural networks were used in classification: fully connected and convolutional neural networks. Within these two categories, further tests were computed via the augmentation of the original 512×512 axial images. Training neural networks over the axial data has proven to be accurate in its classifications with an average five-fold cross validation of 91.43% on the best trained neural network. This result demonstrates that a more general method (i.e. deep learning) can outperform specialized methods that require image dilation and ring-forming subregions on tumors.
Closed loop deep brain stimulation: an evolving technology.
Hosain, Md Kamal; Kouzani, Abbas; Tye, Susannah
2014-12-01
Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.
Neurosurgery of the future: Deep brain stimulations and manipulations.
Nicolaidis, Stylianos
2017-04-01
Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technology will make both DBS and DBM more precise as procedures and will broaden their indications. CLDBS utilizes as feedback a variety of sources of electrophysiological and neurochemical afferent information about the function of the brain structures to be treated or studied. The efferent actions will be either electric, i.e. the classic excitatory or inhibitory ones, or micro-injection of such things as neural proteins and transmitters, neural grafts, implants of pluripotent stem cells or mesenchymal stem cells, and some variants of gene therapy. The pathologies to be treated, beside Parkinson's disease and movement disorders, include repair of neural tissues, neurodegenerative pathologies, psychiatric and behavioral dysfunctions, i.e. schizophrenia in its various guises, bipolar disorders, obesity, anorexia, drug addiction, and alcoholism. The possibility of using these new modalities to treat a number of cognitive dysfunctions is also under consideration. Because the DBS-CLDBS technology brings about a cross-fertilization between scientific investigation and surgical practice, it will also contribute to an enhanced understanding of brain function. Copyright © 2017. Published by Elsevier Inc.
Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder.
Zhao, Yu; Dong, Qinglin; Chen, Hanbo; Iraji, Armin; Li, Yujie; Makkie, Milad; Kou, Zhifeng; Liu, Tianming
2017-12-01
State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with
Material and physical model for evaluation of deep brain activity contribution to EEG recordings
NASA Astrophysics Data System (ADS)
Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen
2015-12-01
Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.
Red and NIR light dosimetry in the human deep brain
NASA Astrophysics Data System (ADS)
Pitzschke, A.; Lovisa, B.; Seydoux, O.; Zellweger, M.; Pfleiderer, M.; Tardy, Y.; Wagnières, G.
2015-04-01
Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson’s Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.
Zador, Zsolt; Magzoub, Mazin; Jin, Songwan; Manley, Geoffrey T; Papadopoulos, Marios C; Verkman, A S
2008-03-01
Diffusion in brain extracellular space (ECS) is important for nonsynaptic intercellular communication, extracellular ionic buffering, and delivery of drugs and metabolites. We measured macromolecular diffusion in normally light-inaccessible regions of mouse brain by microfiberoptic epifluorescence photobleaching, in which a fiberoptic with a micron-size tip is introduced deep in brain tissue. In brain cortex, the diffusion of a noninteracting molecule [fluorescein isothiocyanate (FITC)-dextran, 70 kDa] was slowed 4.5 +/- 0.5-fold compared with its diffusion in water (D(o)/D), and was depth-independent down to 800 microm from the brain surface. Diffusion was significantly accelerated (D(o)/D of 2.9+/-0.3) in mice lacking the glial water channel aquaporin-4. FITC-dextran diffusion varied greatly in different regions of brain, with D(o)/D of 3.5 +/- 0.3 in hippocampus and 7.4 +/- 0.3 in thalamus. Remarkably, D(o)/D in deep brain was strongly dependent on solute size, whereas diffusion in cortex changed little with solute size. Mathematical modeling of ECS diffusion required nonuniform ECS dimensions in deep brain, which we call "heterometricity," to account for the size-dependent diffusion. Our results provide the first data on molecular diffusion in ECS deep in brain in vivo and demonstrate previously unrecognized hindrance and heterometricity for diffusion of large macromolecules in deep brain.
Kainz, Wolfgang; Alesch, François; Chan, Dulciana Dias
2003-01-01
Background The purpose was to investigate mobile phone interference with implantable deep brain stimulators by means of 10 different 900 Mega Hertz (MHz) and 10 different 1800 MHz GSM (Global System for Mobile Communications) mobile phones. Methods All tests were performed in vitro using a phantom especially developed for testing with deep brain stimulators. The phantom was filled with liquid phantom materials simulating brain and muscle tissue. All examinations were carried out inside an anechoic chamber on two implants of the same type of deep brain stimulator: ITREL-III from Medtronic Inc., USA. Results Despite a maximum transmitted peak power of mobile phones of 1 Watt (W) at 1800 MHz and 2 W at 900 MHz respectively, no influence on the ITREL-III was found. Neither the shape of the pulse form changed nor did single pulses fail. Tests with increased transmitted power using CW signals and broadband dipoles have shown that inhibition of the ITREL-III occurs at frequency dependent power levels which are below the emissions of GSM mobile phones. The ITREL-III is essentially more sensitive at 1800 MHz than at 900 MHz. Particularly the frequency range around 1500 MHz shows a very low interference threshold. Conclusion These investigations do not indicate a direct risk for ITREL-III patients using the tested GSM phones. Based on the interference levels found with CW signals, which are below the mobile phone emissions, we recommend similar precautions as for patients with cardiac pacemakers: 1. The phone should be used at the ear at the opposite side of the implant and 2. The patient should avoid carrying the phone close to the implant. PMID:12773204
The treatment of Parkinson's disease with deep brain stimulation: current issues
Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars
2015-01-01
Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation. PMID:26330809
The treatment of Parkinson's disease with deep brain stimulation: current issues.
Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars
2015-07-01
Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.
Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.
2014-01-01
Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229
Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor.
Rezaei Haddad, Ali; Samuel, Michael; Hulse, Natasha; Lin, Hsin-Ying; Ashkan, Keyoumars
2017-07-01
Ventralis intermedius deep brain stimulation is an established intervention for medication-refractory essential tremor. Newer constant current stimulation technology offers theoretical advantage over the traditional constant voltage systems in terms of delivering a more biologically stable therapy. There are no previous reports on the outcomes of constant current deep brain stimulation in the treatment of essential tremor. This study aimed to evaluate the long-term efficacy of ventralis intermedius constant current deep brain stimulation in patients diagnosed with essential tremor. Essential tremor patients implanted with constant current deep brain stimulation for a minimum of three years were evaluated. Clinical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. The quality of life in the patients was assessed using the Quality of Life in Essential Tremor questionnaire. Ten patients were evaluated with a median age at evaluation of 74 years (range 66-79) and a mean follow up time of 49.7 (range 36-78) months since starting stimulation. Constant current ventralis intermedius deep brain stimulation was well tolerated and effective in all patients with a mean score improvement from 50.7 ± 5.9 to 17.4 ± 5.7 (p = 0.0020) in the total Fahn-Tolosa-Marin rating scale score (65.6%). Furthermore, the total combined mean Quality of Life in Essential Tremor score was improved from 56.2 ± 4.9 to 16.8 ± 3.5 (p value = 0.0059) (70.1%). This report shows that long-term constant current ventralis intermedius deep brain stimulation is a safe and effective intervention for essential tremor patients. © 2017 International Neuromodulation Society.
Cheeran, Binith; Pugh, Jonathan; Pycroft, Laurie; Boccard, Sandra; Prangnell, Simon; Green, Alexander L.; FitzGerald, James; Savulescu, Julian; Aziz, Tipu
2017-01-01
Background Innovative neurosurgical treatments present a number of known risks, the natures and probabilities of which can be adequately communicated to patients via the standard procedures governing obtaining informed consent. However, due to their novelty, these treatments also come with unknown risks, which require an augmented approach to obtaining informed consent. Objective This paper aims to discuss and provide concrete procedural guidance on the ethical issues raised by serious unexpected complications of novel deep brain stimulation treatments. Approach We illustrate our analysis using a case study of the unexpected development of recurrent stereotyped events in patients following the use of deep brain stimulation (DBS) to treat severe chronic pain. Examining these unexpected complications in light of medical ethical principles, we argue that serious complications of novel DBS treatments do not necessarily make it unethical to offer the intervention to eligible patients. However, the difficulty the clinician faces in determining whether the intervention is in the patient's best interests generates reasons to take extra steps to promote the autonomous decision making of these patients. Conclusion and recommendations We conclude with clinical recommendations, including details of an augmented consent process for novel DBS treatment. PMID:28557242
Network effects of deep brain stimulation
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
EKG-based detection of deep brain stimulation in fMRI studies.
Fiveland, Eric; Madhavan, Radhika; Prusik, Julia; Linton, Renee; Dimarzio, Marisa; Ashe, Jeffrey; Pilitsis, Julie; Hancu, Ileana
2018-04-01
To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram-based triggering system METHODS: A detector for measuring and predicting the on/off state of cycling deep brain stimulation was developed and tested in six patients in office visits. Three-electrode electrocardiogram measurements, amplified by a commercial bio-amplifier, were used as input for a custom electronics box (e-box). The e-box transformed the deep brain stimulation waveforms into transistor-transistor logic pulses, recorded their timing, and propagated it in time. The e-box was used to trigger task-based deep brain stimulation functional MRI scans in 5 additional subjects; the impact of timing accuracy on t-test values was investigated in a simulation study using the functional MRI data. Following locking to each patient's individual waveform, the e-box was shown to predict stimulation onset with an average absolute error of 112 ± 148 ms, 30 min after disconnecting from the patients. The subsecond accuracy of the e-box in predicting timing onset is more than adequate for our slow varying, 30-/30-s on/off stimulation paradigm. Conversely, the experimental deep brain stimulation onset prediction accuracy in the absence of the e-box, which could be off by as much as 4 to 6 s, could significantly decrease activation strength. Using this detector, stimulation can be accurately synchronized to functional MRI acquisitions, without adding any additional hardware in the MRI environment. Magn Reson Med 79:2432-2439, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.
NASA Astrophysics Data System (ADS)
Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.
2017-05-01
Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.
Automated deep-phenotyping of the vertebrate brain
Allalou, Amin; Wu, Yuelong; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih
2017-01-01
Here, we describe an automated platform suitable for large-scale deep-phenotyping of zebrafish mutant lines, which uses optical projection tomography to rapidly image brain-specific gene expression patterns in 3D at cellular resolution. Registration algorithms and correlation analysis are then used to compare 3D expression patterns, to automatically detect all statistically significant alterations in mutants, and to map them onto a brain atlas. Automated deep-phenotyping of a mutation in the master transcriptional regulator fezf2 not only detects all known phenotypes but also uncovers important novel neural deficits that were overlooked in previous studies. In the telencephalon, we show for the first time that fezf2 mutant zebrafish have significant patterning deficits, particularly in glutamatergic populations. Our findings reveal unexpected parallels between fezf2 function in zebrafish and mice, where mutations cause deficits in glutamatergic neurons of the telencephalon-derived neocortex. DOI: http://dx.doi.org/10.7554/eLife.23379.001 PMID:28406399
Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics
NASA Astrophysics Data System (ADS)
Chen, Shuo; Weitemier, Adam Z.; Zeng, Xiao; He, Linmeng; Wang, Xiyu; Tao, Yanqiu; Huang, Arthur J. Y.; Hashimotodani, Yuki; Kano, Masanobu; Iwasaki, Hirohide; Parajuli, Laxmi Kumar; Okabe, Shigeo; Teh, Daniel B. Loong; All, Angelo H.; Tsutsui-Kimura, Iku; Tanaka, Kenji F.; Liu, Xiaogang; McHugh, Thomas J.
2018-02-01
Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.
Pathways of translation: deep brain stimulation.
Gionfriddo, Michael R; Greenberg, Alexandra J; Wahegaonkar, Abhijeet L; Lee, Kendall H
2013-12-01
Electrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high-frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench-to-bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench. © 2013 Wiley Periodicals, Inc.
Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E
2017-09-01
Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.
Flexible deep brain neural probes based on a parylene tube structure
NASA Astrophysics Data System (ADS)
Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong
2018-01-01
Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.
Brain tumor classification of microscopy images using deep residual learning
NASA Astrophysics Data System (ADS)
Ishikawa, Yota; Washiya, Kiyotada; Aoki, Kota; Nagahashi, Hiroshi
2016-12-01
The crisis rate of brain tumor is about one point four in ten thousands. In general, cytotechnologists take charge of cytologic diagnosis. However, the number of cytotechnologists who can diagnose brain tumors is not sufficient, because of the necessity of highly specialized skill. Computer-Aided Diagnosis by computational image analysis may dissolve the shortage of experts and support objective pathological examinations. Our purpose is to support a diagnosis from a microscopy image of brain cortex and to identify brain tumor by medical image processing. In this study, we analyze Astrocytes that is a type of glia cell of central nerve system. It is not easy for an expert to discriminate brain tumor correctly since the difference between astrocytes and low grade astrocytoma (tumors formed from Astrocyte) is very slight. In this study, we present a novel method to segment cell regions robustly using BING objectness estimation and to classify brain tumors using deep convolutional neural networks (CNNs) constructed by deep residual learning. BING is a fast object detection method and we use pretrained BING model to detect brain cells. After that, we apply a sequence of post-processing like Voronoi diagram, binarization, watershed transform to obtain fine segmentation. For classification using CNNs, a usual way of data argumentation is applied to brain cells database. Experimental results showed 98.5% accuracy of classification and 98.2% accuracy of segmentation.
Viaña, John Noel M; Gilbert, Frederic
2018-01-01
Memory dysfunction and cognitive impairments due to Alzheimer's disease can affect the selfhood and identity of afflicted individuals, causing distress to both people with Alzheimer's disease and their caregivers. Recently, a number of case studies and clinical trials have been conducted to determine the potential of deep brain stimulation as a therapeutic modality for people with Alzheimer's disease. Some of these studies have shown that deep brain stimulation could induce flashbacks and stabilize or even improve memory. However, deep brain stimulation itself has also been attributed as a potential threat to identity and selfhood, especially when procedure-related adverse events arise. We anticipate potential effects of deep brain stimulation for people with Alzheimer's disease on selfhood, reconciling information from medical reports, psychological, and sociological investigations on the impacts of deep brain stimulation or Alzheimer's disease on selfhood. A tripartite model of the self that extends the scope of Rom Harré's and Steve Sabat's social constructionist framework was used. In this model, potential effects of deep brain stimulation for Alzheimer's disease on Self 1 or singularity through use of first-person indexicals, and gestures of self-reference, attribution, and recognition; Self 2 or past and present attributes, knowledge of these characteristics, and continuity of narrative identity; and Self 3 or the relational and social self are explored. The ethical implications of potential effects of deep brain stimulation for Alzheimer's disease on the tripartite self are then highlighted, focusing on adapting informed consent procedures and care provided throughout the trial to account for both positive and negative plausible effects on Self 1, Self 2, and Self 3.
A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.
Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael
2013-01-01
Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.
Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis
2017-09-01
Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep
Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom
2014-04-01
Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.
Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report.
Ho, Allen L; Choudhri, Omar; Sung, C Kwang; DiRenzo, Elizabeth E; Halpern, Casey H
2015-03-01
Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS).
Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report
Choudhri, Omar; Sung, C. Kwang; DiRenzo, Elizabeth E; Halpern, Casey H
2015-01-01
Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS). PMID:26180680
Deep Brain Electrical Stimulation in Epilepsy
NASA Astrophysics Data System (ADS)
Rocha, Luisa L.
2008-11-01
The deep brain electrical stimulation has been used for the treatment of neurological disorders such as Parkinson's disease, chronic pain, depression and epilepsy. Studies carried out in human brain indicate that the application of high frequency electrical stimulation (HFS) at 130 Hz in limbic structures of patients with intractable temporal lobe epilepsy abolished clinical seizures and significantly decreased the number of interictal spikes at focus. The anticonvulsant effects of HFS seem to be more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss. In addition, experiments using models of epilepsy indicate that HFS (pulses of 60 μs width at 130 Hz at subthreshold current intensity) of specific brain areas avoids the acquisition of generalized seizures and enhances the postictal seizure suppression. HFS is also able to modify the status epilepticus. It is concluded that the effects of HFS may be a good strategy to reduce or avoid the epileptic activity.
Deep Brain Stimulation using Magnetic Fields
NASA Astrophysics Data System (ADS)
Jiles, David; Williams, Paul; Crowther, Lawrence; Iowa State University Team; Wolfson CentreMagnetics Team
2011-03-01
New applications for transcranial magnetic stimulation are developing rapidly for both diagnostic and therapeutic purposes. Therefore so is the demand for improved performance, particularly in terms of their ability to stimulate deeper regions of the brain and to do so selectively. The coil designs that are used presently are limited in their ability to stimulate the brain at depth and with high spatial focality. Consequently, any improvement in coil performance would have a significant impact in extending the usefulness of TMS in both clinical applications and academic research studies. New and improved coil designs have then been developed, modeled and tested as a result of this work. A large magnetizing coil, 300mm in diameter and compatible with a commercial TMS system has been constructed to determine its feasibility for use as a deep brain stimulator. The results of this work have suggested directions that could be pursued in order to further improve the coil designs.
Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C
2011-08-15
Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.
Effects of deep brain stimulation in dyskinetic cerebral palsy: a meta-analysis.
Koy, Anne; Hellmich, Martin; Pauls, K Amande M; Marks, Warren; Lin, Jean-Pierre; Fricke, Oliver; Timmermann, Lars
2013-05-01
Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P < .001) at a median follow-up of 12 months. The mean Burke-Fahn-Marsden Dystonia Rating Scale disability score was 18.54 ± 6.15 preoperatively and 16.83 ± 6.42 postoperatively, with a mean improvement of 9.2% (P < .001). There was a significant negative correlation between severity of dystonia and clinical outcome (P < .05). Deep brain stimulation can be an effective treatment option for dyskinetic cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.
Schneider, Frank; Habel, Ute; Volkmann, Jens; Regel, Sabine; Kornischka, Jürgen; Sturm, Volker; Freund, Hans-Joachim
2003-03-01
High-frequency electrical stimulation of the subthalamic nucleus is a new and highly effective therapy for complications of long-term levodopa therapy and motor symptoms in advanced Parkinson disease (PD). Clinical observations indicate additional influence on emotional behavior. Electrical stimulation of deep brain nuclei with pulse rates above 100 Hz provokes a reversible, lesioning-like effect. Here, the effect of deep brain stimulation of the subthalamic nucleus on emotional, cognitive, and motor performance in patients with PD (n = 12) was examined. The results were compared with the effects of a suprathreshold dose of levodopa intended to transiently restore striatal dopamine deficiency. Patients were tested during medication off/stimulation off (STIM OFF), medication off/stimulation on (STIM ON), and during the best motor state after taking levodopa without deep brain stimulation (MED). More positive self-reported mood and an enhanced mood induction effect as well as improvement in emotional memory during STIM ON were observed, while during STIM OFF, patients revealed reduced emotional performance. Comparable effects were revealed by STIM ON and MED. Cognitive performance was not affected by the different conditions and treatments. Deep brain stimulation of the subthalamic nucleus selectively enhanced affective processing and subjective well-being and seemed to be antidepressive. Levodopa and deep brain stimulation had similar effects on emotion. This finding may provide new clues about the neurobiologic bases of emotion and mood disorders, and it illustrates the important role of the basal ganglia and the dopaminergic system in emotional processing in addition to the well-known motor and cognitive functions.
Chakraborty, Shamik; Lall, Rohan; Fanous, Andrew A; Boockvar, John; Langer, David J
2017-01-01
The surgical management of deep brain tumors is often challenging due to the limitations of stereotactic needle biopsies and the morbidity associated with transcortical approaches. We present a novel microscopic navigational technique utilizing the Viewsite Brain Access System (VBAS) (Vycor Medical, Boca Raton, FL, USA) for resection of a deep parietal periventricular high-grade glioma as well as another glioma and a cavernoma with no related morbidity. The approach utilized a navigational tracker mounted on a microscope, which was set to the desired trajectory and depth. It allowed gentle continuous insertion of the VBAS directly to a deep lesion under continuous microscopic visualization, increasing safety by obviating the need to look up from the microscope and thus avoiding loss of trajectory. This technique has broad value for the resection of a variety of deep brain lesions. PMID:28331774
White, Tim; Chakraborty, Shamik; Lall, Rohan; Fanous, Andrew A; Boockvar, John; Langer, David J
2017-02-04
The surgical management of deep brain tumors is often challenging due to the limitations of stereotactic needle biopsies and the morbidity associated with transcortical approaches. We present a novel microscopic navigational technique utilizing the Viewsite Brain Access System (VBAS) (Vycor Medical, Boca Raton, FL, USA) for resection of a deep parietal periventricular high-grade glioma as well as another glioma and a cavernoma with no related morbidity. The approach utilized a navigational tracker mounted on a microscope, which was set to the desired trajectory and depth. It allowed gentle continuous insertion of the VBAS directly to a deep lesion under continuous microscopic visualization, increasing safety by obviating the need to look up from the microscope and thus avoiding loss of trajectory. This technique has broad value for the resection of a variety of deep brain lesions.
Mavridis, Ioannis N
2017-12-11
The concept of stereotactically standard areas (SSAs) within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.
Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice
Zhang, Qian; Castellanos Rubio, Idoia; del Pino, Pablo
2017-01-01
Establishing how neurocircuit activation causes particular behaviors requires modulating the activity of specific neurons. Here, we demonstrate that magnetothermal genetic stimulation provides tetherless deep brain activation sufficient to evoke motor behavior in awake mice. The approach uses alternating magnetic fields to heat superparamagnetic nanoparticles on the neuronal membrane. Neurons, heat-sensitized by expressing TRPV1 are activated with magnetic field application. Magnetothermal genetic stimulation in the motor cortex evoked ambulation, deep brain stimulation in the striatum caused rotation around the body-axis, and stimulation near the ridge between ventral and dorsal striatum caused freezing-of-gait. The duration of the behavior correlated tightly with field application. This approach provides genetically and spatially targetable, repeatable and temporarily precise activation of deep-brain circuits without the need for surgical implantation of any device. PMID:28826470
Concussion classification via deep learning using whole-brain white matter fiber strains
Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang
2018-01-01
Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828–0.862 vs. 0.690–0.776, and .632+ error of 0.148–0.176 vs. 0.207–0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury. PMID:29795640
Concussion classification via deep learning using whole-brain white matter fiber strains.
Cai, Yunliang; Wu, Shaoju; Zhao, Wei; Li, Zhigang; Wu, Zheyang; Ji, Songbai
2018-01-01
Developing an accurate and reliable injury predictor is central to the biomechanical studies of traumatic brain injury. State-of-the-art efforts continue to rely on empirical, scalar metrics based on kinematics or model-estimated tissue responses explicitly pre-defined in a specific brain region of interest. They could suffer from loss of information. A single training dataset has also been used to evaluate performance but without cross-validation. In this study, we developed a deep learning approach for concussion classification using implicit features of the entire voxel-wise white matter fiber strains. Using reconstructed American National Football League (NFL) injury cases, leave-one-out cross-validation was employed to objectively compare injury prediction performances against two baseline machine learning classifiers (support vector machine (SVM) and random forest (RF)) and four scalar metrics via univariate logistic regression (Brain Injury Criterion (BrIC), cumulative strain damage measure of the whole brain (CSDM-WB) and the corpus callosum (CSDM-CC), and peak fiber strain in the CC). Feature-based machine learning classifiers including deep learning, SVM, and RF consistently outperformed all scalar injury metrics across all performance categories (e.g., leave-one-out accuracy of 0.828-0.862 vs. 0.690-0.776, and .632+ error of 0.148-0.176 vs. 0.207-0.292). Further, deep learning achieved the best cross-validation accuracy, sensitivity, AUC, and .632+ error. These findings demonstrate the superior performances of deep learning in concussion prediction and suggest its promise for future applications in biomechanical investigations of traumatic brain injury.
Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter
2016-05-01
Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the
[Stereotactic biopsy in the accurate diagnosis of lesions in the brain stem and deep brain].
Qin, F; Huang, Z C; Cai, M Q; Xu, X F; Lu, T T; Dong, Q; Wu, A M; Lu, Z Z; Zhao, C; Guo, Y
2018-06-12
Objective: To investigate the value of stereotactic biopsy in the accurate diagnosis of lesions in the brain stem and deep brain. Methods: A total of 29 consecutive patients who underwent stereotactic biopsy of brainstem and deep brain lesions between May 2012 and January 2018 were retrospectively reviewed. The Cosman-Roberts-Wells (CRW) stereotactic frame was installed under local anesthesia. Thin-layer CT and MRI scanning were performed. Target coordinates were calculated by inputting CT-MRI data into the radionics surgical planning system. The individualized puncture path was designed according to the location of the lesions and the characteristics of the image. Target distributions were as follows: 12 cases of midbrain or pons, 2 cases of internal capsule, 3 cases of thalamus, 12 cases of basal ganglia. The biopsy samples were used for further pathological and/or genetic diagnosis. Results: Twenty-eight of the 29 cases (96.6%) were diagnosed accurately by histopathology and genomic examination following stereotactic biopsy. Pathological results were as follows: 8 cases of lymphoma, 7 cases of glioma, 4 cases of demyelination, 2 cases of germ cell tumor, 2 cases of metastatic tumor, 1 cases of cerebral sparganosis, 1 case of tuberculous granuloma, 1 case of hereditary prion disease, 1 case of glial hyperplasia, 1 case of leukemia. The accurate diagnosis of one case required a combination of histopathology and genomic examination. Undefined diagnosis was still made in 1 cases (3.45%) after biopsy. After biopsy, there were 2 cases (6.9%) with symptomatic slight hemorrhage, 1 case (3.45%) with symptomatic severe hemorrhage, and 1 cass (3.45%) with permanent neurological dysfunction. No one died because of surgery or surgical complications. Conclusions: Stereotactic biopsy is fast, safe and minimally invasive. It is an ideal strategy for accurate diagnosis of lesions in brain stem and deep brain.
Regional anatomy of the pedunculopontine nucleus: relevance for deep brain stimulation.
Fournier-Gosselin, Marie-Pierre; Lipsman, Nir; Saint-Cyr, Jean A; Hamani, Clement; Lozano, Andres M
2013-09-01
The pedunculopontine nucleus (PPN) is currently being investigated as a potential deep brain stimulation target to improve gait and posture in Parkinson's disease. This review examines the complex anatomy of the PPN region and suggests a functional mapping of the surrounding nuclei and fiber tracts that may serve as a guide to a more accurate placement of electrodes while avoiding potentially adverse effects. The relationships of the PPN were examined in different human brain atlases. Schematic representations of those structures in the vicinity of the PPN were generated and correlated with their potential stimulation effects. By providing a functional map and representative schematics of the PPN region, we hope to optimize the placement of deep brain stimulation electrodes, thereby maximizing safety and clinical efficacy. © 2013 International Parkinson and Movement Disorder Society.
MRI-induced heating of deep brain stimulation leads
NASA Astrophysics Data System (ADS)
Mohsin, Syed A.; Sheikh, Noor M.; Saeed, Usman
2008-10-01
The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.
Designing a deep brain stimulator to suppress pathological neuronal synchrony.
Montaseri, Ghazal; Yazdanpanah, Mohammad Javad; Bahrami, Fariba
2015-03-01
Some of neuropathologies are believed to be related to abnormal synchronization of neurons. In the line of therapy, designing effective deep brain stimulators to suppress the pathological synchrony among neuronal ensembles is a challenge of high clinical relevance. The stimulation should be able to disrupt the synchrony in the presence of latencies due to imperfect knowledge about parameters of a neuronal ensemble and stimulation impacts on the ensemble. We propose an adaptive desynchronizing deep brain stimulator capable of dealing with these uncertainties. We analyze the collective behavior of the stimulated neuronal ensemble and show that, using the designed stimulator, the resulting asynchronous state is stable. Simulation results reveal the efficiency of the proposed technique. Copyright © 2014 Elsevier Ltd. All rights reserved.
Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C
2016-01-01
Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255
Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir
2016-01-01
Abstract Chronic dopamine depletion in Parkinson’s disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus–cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These
Deep brain stimulation of the internal pallidum in multiple system atrophy.
Santens, Patrick; Patrick, Santens; Vonck, Kristl; Kristl, Vonck; De Letter, Miet; Miet, De Letter; Van Driessche, Katya; Katya, Van Driessche; Sieben, Anne; Anne, Sieben; De Reuck, Jacques; Jacques, De Reuck; Van Roost, Dirk; Dirk, Van Roost; Boon, Paul; Paul, Boon
2006-04-01
We describe the outcome of deep brain stimulation of the internal pallidum in a 57-year old patient with multiple system atrophy. Although the prominent dystonic features of this patient were markedly attenuated post-operatively, the outcome was to be considered unfavourable. There was a severe increase in akinesia resulting in overall decrease of mobility in limbs as well as in the face. As a result, the patient was anarthric and displayed dysphagia. A laterality effect of stimulation on oro-facial movements was demonstrated. The patient died 7 months post-operatively. This report adds to the growing consensus that multiple system atrophy patients are unsuitable candidates for deep brain stimulation.
Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G
2017-05-01
Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.
Mechanisms of deep brain stimulation
Cheng, Jennifer J.; Eskandar, Emad N.
2015-01-01
Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. PMID:26510756
Two-step tunneling technique of deep brain stimulation extension wires-a description.
Fontaine, Denys; Vandersteen, Clair; Saleh, Christian; von Langsdorff, Daniel; Poissonnet, Gilles
2013-12-01
While a significant body of literature exists on the intracranial part of deep brain stimulation surgery, the equally important second part of the intervention related to the subcutaneous tunneling of deep brain stimulation extension wires is rarely described. The tunneling strategy can consist of a single passage of the extension wires from the frontal incision site to the subclavicular area, or of a two-step approach that adds a retro-auricular counter-incision. Each technique harbors the risk of intraoperative and postoperative complications. At our center, we perform a two-step tunneling procedure that we developed based on a cadaveric study. In 125 consecutive patients operated since 2002, we did not encounter any complication related to our tunneling method. Insufficient data exist to fully evaluate the advantages and disadvantages of each tunneling technique. It is of critical importance that authors detail their tunneling modus operandi and report the presence or absence of complications. This gathered data pool may help to formulate a definitive conclusions on the safest method for subcutaneous tunneling of extension wires in deep brain stimulation.
Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R
2009-01-01
This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.
Weaver, Frances M; Follett, Kenneth; Stern, Matthew; Hur, Kwan; Harris, Crystal; Marks, William J; Rothlind, Johannes; Sagher, Oren; Reda, Domenic; Moy, Claudia S; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C; Duda, John E; Holloway, Kathryn; Samii, Ali; Horn, Stacy; Bronstein, Jeff; Stoner, Gatana; Heemskerk, Jill; Huang, Grant D
2009-01-07
Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists. The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small
Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl
2014-01-01
Depleted of dopamine, the dynamics of the parkinsonian brain impact on both ‘action’ and ‘resting’ motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the ‘effective’ connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670
Electrical engram: how deep brain stimulation affects memory.
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.
Primary experimental study on safety of deep brain stimulation in RF electromagnetic field.
Jun, Xu; Luming, Li; Hongwei, Hao
2009-01-01
With the rapid growth of clinical application of Deep Brain Stimulation, its safety and functional concern in the electromagnetic field, another pollution becoming much more serious, has become more and more significant. Meanwhile, the measuring standards on Electromagnetic Compatibility (EMC) for DBS are still incomplete. Particularly, the knowledge of the electromagnetic field induced signals on the implanted lead is ignorant while some informal reports some side effects. This paper briefly surmised the status of EMC standards on implantable medical devices. Based on the EMC experiments of DBS device we developed, two experiments for measuring the induced voltage of the deep brain stimulator in RF electromagnetic field were reported. The measured data showed that the induced voltage in some frequency was prominent, for example over 2V. As a primary research, we think these results would be significant to cause researcher to pay more attention to the EMC safety problem and biological effects of the induced voltage in deep brain stimulation and other implantable devices.
[Deep brain stimulation in movement disorders: evidence and therapy standards].
Parpaley, Yaroslav; Skodda, Sabine
2017-07-01
The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice. Georg Thieme Verlag KG Stuttgart · New York.
Manifold learning of brain MRIs by deep learning.
Brosch, Tom; Tam, Roger
2013-01-01
Manifold learning of medical images plays a potentially important role for modeling anatomical variability within a population with pplications that include segmentation, registration, and prediction of clinical parameters. This paper describes a novel method for learning the manifold of 3D brain images that, unlike most existing manifold learning methods, does not require the manifold space to be locally linear, and does not require a predefined similarity measure or a prebuilt proximity graph. Our manifold learning method is based on deep learning, a machine learning approach that uses layered networks (called deep belief networks, or DBNs) and has received much attention recently in the computer vision field due to their success in object recognition tasks. DBNs have traditionally been too computationally expensive for application to 3D images due to the large number of trainable parameters. Our primary contributions are (1) a much more computationally efficient training method for DBNs that makes training on 3D medical images with a resolution of up to 128 x 128 x 128 practical, and (2) the demonstration that DBNs can learn a low-dimensional manifold of brain volumes that detects modes of variations that correlate to demographic and disease parameters.
TuMore: generation of synthetic brain tumor MRI data for deep learning based segmentation approaches
NASA Astrophysics Data System (ADS)
Lindner, Lydia; Pfarrkirchner, Birgit; Gsaxner, Christina; Schmalstieg, Dieter; Egger, Jan
2018-03-01
Accurate segmentation and measurement of brain tumors plays an important role in clinical practice and research, as it is critical for treatment planning and monitoring of tumor growth. However, brain tumor segmentation is one of the most challenging tasks in medical image analysis. Since manual segmentations are subjective, time consuming and neither accurate nor reliable, there exists a need for objective, robust and fast automated segmentation methods that provide competitive performance. Therefore, deep learning based approaches are gaining interest in the field of medical image segmentation. When the training data set is large enough, deep learning approaches can be extremely effective, but in domains like medicine, only limited data is available in the majority of cases. Due to this reason, we propose a method that allows to create a large dataset of brain MRI (Magnetic Resonance Imaging) images containing synthetic brain tumors - glioblastomas more specifically - and the corresponding ground truth, that can be subsequently used to train deep neural networks.
Deep brain stimulation for movement disorders.
Thevathasan, Wesley; Gregory, Ralph
2010-02-01
Deep brain stimulation is now considered a routine treatment option for selected patients with advanced Parkinson's disease, primary segmental and generalised dystonia, and essential tremor. The neurosurgeon is responsible for the accurate and safe placement of the electrodes and the neurologist for the careful selection of patients and titration of medication against the effects of stimulation. A multidisciplinary team approach involving specialist nurses, neuropsychologists and neurophysiologists is required for a successful outcome. In this article we will summarise the key points in patient selection, provide an overview of the surgical technique, and discuss the beneficial and adverse outcomes that can occur.
Deep brain stimulation for the treatment of uncommon tremor syndromes.
Ramirez-Zamora, Adolfo; Okun, Michael S
2016-08-01
Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson's disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. In this article, we conducted a PubMed search using different combinations between the terms 'Uncommon tremors', 'Dystonic tremor', 'Holmes tremor' 'Midbrain tremor', 'Rubral tremor', 'Cerebellar tremor', 'outflow tremor', 'Multiple Sclerosis tremor', 'Post-traumatic tremor', 'Neuropathic tremor', and 'Deep Brain Stimulation/DBS'. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert commentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features.
Deep brain stimulation for psychiatric disorders: where we are now.
Cleary, Daniel R; Ozpinar, Alp; Raslan, Ahmed M; Ko, Andrew L
2015-06-01
Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.
Shielded battery syndrome: a new hardware complication of deep brain stimulation.
Chelvarajah, Ramesh; Lumsden, Daniel; Kaminska, Margaret; Samuel, Michael; Hulse, Natasha; Selway, Richard P; Lin, Jean-Pierre; Ashkan, Keyoumars
2012-01-01
Deep brain stimulation hardware is constantly advancing. The last few years have seen the introduction of rechargeable cell technology into the implanted pulse generator design, allowing for longer battery life and fewer replacement operations. The Medtronic® system requires an additional pocket adaptor when revising a non-rechargeable battery such as their Kinetra® to their rechargeable Activa® RC. This additional hardware item can, if it migrates superficially, become an impediment to the recharging of the battery and negate the intended technological advance. To report the emergence of the 'shielded battery syndrome', which has not been previously described. We reviewed our deep brain stimulation database to identify cases of recharging difficulties reported by patients with Activa RC implanted pulse generators. Two cases of shielded battery syndrome were identified. The first required surgery to reposition the adaptor to the deep aspect of the subcutaneous pocket. In the second case, it was possible to perform external manual manipulation to restore the adaptor to its original position deep to the battery. We describe strategies to minimise the occurrence of the shielded battery syndrome and advise vigilance in all patients who experience difficulty with recharging after replacement surgery of this type for the implanted pulse generator. Copyright © 2012 S. Karger AG, Basel.
Brain Tumor Segmentation Using Deep Belief Networks and Pathological Knowledge.
Zhan, Tianming; Chen, Yi; Hong, Xunning; Lu, Zhenyu; Chen, Yunjie
2017-01-01
In this paper, we propose an automatic brain tumor segmentation method based on Deep Belief Networks (DBNs) and pathological knowledge. The proposed method is targeted against gliomas (both low and high grade) obtained in multi-sequence magnetic resonance images (MRIs). Firstly, a novel deep architecture is proposed to combine the multi-sequences intensities feature extraction with classification to get the classification probabilities of each voxel. Then, graph cut based optimization is executed on the classification probabilities to strengthen the spatial relationships of voxels. At last, pathological knowledge of gliomas is applied to remove some false positives. Our method was validated in the Brain Tumor Segmentation Challenge 2012 and 2013 databases (BRATS 2012, 2013). The performance of segmentation results demonstrates our proposal providing a competitive solution with stateof- the-art methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Deep learning and texture-based semantic label fusion for brain tumor segmentation
NASA Astrophysics Data System (ADS)
Vidyaratne, L.; Alam, M.; Shboul, Z.; Iftekharuddin, K. M.
2018-02-01
Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.
Deep Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.
Vidyaratne, L; Alam, M; Shboul, Z; Iftekharuddin, K M
2018-01-01
Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.
Chopra, Amit; Abulseoud, Osama A; Sampson, Shirlene; Lee, Kendall H; Klassen, Bryan T; Fields, Julie A; Matsumoto, Joseph Y; Adams, Andrea C; Stoppel, Cynthia J; Geske, Jennifer R; Frye, Mark A
2014-01-01
Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment. © 2013 Published by The Academy of Psychosomatic Medicine on behalf of The Academy of Psychosomatic Medicine.
Schiff, Nicholas D
2013-01-01
This chapter considers the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the minimally conscious state (MCS). CT/DBS for selected patients in a MCS is first placed in the historical context of prior efforts to use thalamic electrical brain stimulation to treat the unconscious clinical conditions of coma and vegetative state. These previous studies and a proof of concept result from a single-subject study of a patient in a MCS are reviewed against the background of new population data providing benchmarks of the natural history of vegetative and MCSs. The conceptual foundations for CT/DBS in selected patients in a MCS are then presented with consideration of both circuit and cellular mechanisms underlying recovery of consciousness identified from empirical studies. Directions for developing future generalizable criteria for CT/DBS that focus on the integrity of necessary brain systems and behavioral profiles in patients in a MCS that may optimally response to support of arousal regulation mechanisms are proposed. © 2013 Elsevier B.V. All rights reserved.
Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Ip, Vincent H L; Wong, Adrian; Kuo, S H; Chan, Danny T M; Zhu, X L; Wong, Edith; Lau, Claire K Y; Wong, Rosanna K M; Tang, Venus; Lau, Christine; Poon, W S
2014-12-01
To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. Case series. Prince of Wales Hospital, Hong Kong. A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.
Deep-Brain Stimulation for Basal Ganglia Disorders.
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.
DeepNAT: Deep convolutional neural network for segmenting neuroanatomy.
Wachinger, Christian; Reuter, Martin; Klein, Tassilo
2018-04-15
We introduce DeepNAT, a 3D Deep convolutional neural network for the automatic segmentation of NeuroAnaTomy in T1-weighted magnetic resonance images. DeepNAT is an end-to-end learning-based approach to brain segmentation that jointly learns an abstract feature representation and a multi-class classification. We propose a 3D patch-based approach, where we do not only predict the center voxel of the patch but also neighbors, which is formulated as multi-task learning. To address a class imbalance problem, we arrange two networks hierarchically, where the first one separates foreground from background, and the second one identifies 25 brain structures on the foreground. Since patches lack spatial context, we augment them with coordinates. To this end, we introduce a novel intrinsic parameterization of the brain volume, formed by eigenfunctions of the Laplace-Beltrami operator. As network architecture, we use three convolutional layers with pooling, batch normalization, and non-linearities, followed by fully connected layers with dropout. The final segmentation is inferred from the probabilistic output of the network with a 3D fully connected conditional random field, which ensures label agreement between close voxels. The roughly 2.7million parameters in the network are learned with stochastic gradient descent. Our results show that DeepNAT compares favorably to state-of-the-art methods. Finally, the purely learning-based method may have a high potential for the adaptation to young, old, or diseased brains by fine-tuning the pre-trained network with a small training sample on the target application, where the availability of larger datasets with manual annotations may boost the overall segmentation accuracy in the future. Copyright © 2017 Elsevier Inc. All rights reserved.
Deep brain stimulation mechanisms: beyond the concept of local functional inhibition.
Deniau, Jean-Michel; Degos, Bertrand; Bosch, Clémentine; Maurice, Nicolas
2010-10-01
Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Haynes, W I A; Millet, B; Mallet, L
2012-01-01
Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Andrews, Russell J
2003-05-01
Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.
NASA Technical Reports Server (NTRS)
Andrews, Russell J.
2003-01-01
Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.
Sing the mind electric - principles of deep brain stimulation.
Kringelbach, Morten L; Green, Alexander L; Owen, Sarah L F; Schweder, Patrick M; Aziz, Tipu Z
2010-10-01
The remarkable efficacy of deep brain stimulation (DBS) for a range of treatment-resistant disorders is still not matched by a comparable understanding of the underlying neural mechanisms. Some progress has been made using translational research with a range of neuroscientific techniques, and here we review the most promising emerging principles. On balance, DBS appears to work by restoring normal oscillatory activity between a network of key brain regions. Further research using this causal neuromodulatory tool may provide vital insights into fundamental brain function, as well as guide targets for future treatments. In particular, DBS could have an important role in restoring the balance of the brain's default network and thus repairing the malignant brain states associated with affective disorders, which give rise to serious disabling problems such as anhedonia, the lack of pleasure. At the same time, it is important to proceed with caution and not repeat the errors from the era of psychosurgery. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Affect of deep brain stimulation on limb paresis after stroke.
Phillips, N I; Bhakta, B B
2000-07-15
A deep brain stimulator was implanted in the periventricular grey matter of the third ventricle for pain after stroke in a man aged 48 years. As well as a beneficial analgesic effect, the patient reported improved function in the contralateral paretic arm, which was confirmed on formal testing.
Deep-Brain Stimulation for Basal Ganglia Disorders
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
Deep brain stimulation for the treatment of uncommon tremor syndromes
Ramirez-Zamora, Adolfo; Okun, Michael S.
2016-01-01
ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert c ommentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features. PMID:27228280
Singh, Harnarayan; Patir, Rana; Vaishya, Sandeep; Miglani, Rahul; Kaur, Amandeep
2018-06-01
Minimally invasive transportal resection of deep intracranial lesions has become a widely accepted surgical technique. Many disposable, mountable port systems are available in the market for this purpose, like the ViewSite Brain Access System. The objective of this study was to find a cost-effective substitute for these systems. Deep-seated brain lesions were treated with a port system made from disposable syringes. The syringe port could be inserted through minicraniotomies placed and planned with navigation. All deep-seated lesions like ventricular tumours, colloid cysts, deep-seated gliomas, and basal ganglia hemorrhages were treated with this syringe port system and evaluated for safety, operative site hematomas, and blood loss. 62 patients were operated on during the study period from January 2015 to July 2017, using this innovative syringe port system for deep-seated lesions of the brain. No operative site hematoma or contusions were seen along the port entry site and tract. Syringe port is a cost-effective and safe alternative to the costly disposable brain port systems, especially for neurosurgical setups in developing countries for minimally invasive transportal resection of deep brain lesions. Copyright © 2018 Elsevier Inc. All rights reserved.
Deep ensemble learning of sparse regression models for brain disease diagnosis
Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang
2018-01-01
Recent studies on brain imaging analysis witnessed the core roles of machine learning techniques in computer-assisted intervention for brain disease diagnosis. Of various machine-learning techniques, sparse regression models have proved their effectiveness in handling high-dimensional data but with a small number of training samples, especially in medical problems. In the meantime, deep learning methods have been making great successes by outperforming the state-of-the-art performances in various applications. In this paper, we propose a novel framework that combines the two conceptually different methods of sparse regression and deep learning for Alzheimer’s disease/mild cognitive impairment diagnosis and prognosis. Specifically, we first train multiple sparse regression models, each of which is trained with different values of a regularization control parameter. Thus, our multiple sparse regression models potentially select different feature subsets from the original feature set; thereby they have different powers to predict the response values, i.e., clinical label and clinical scores in our work. By regarding the response values from our sparse regression models as target-level representations, we then build a deep convolutional neural network for clinical decision making, which thus we call ‘ Deep Ensemble Sparse Regression Network.’ To our best knowledge, this is the first work that combines sparse regression models with deep neural network. In our experiments with the ADNI cohort, we validated the effectiveness of the proposed method by achieving the highest diagnostic accuracies in three classification tasks. We also rigorously analyzed our results and compared with the previous studies on the ADNI cohort in the literature. PMID:28167394
Chen, Shengdi; Gao, Guodong; Feng, Tao; Zhang, Jianguo
2018-01-01
Deep Brain Stimulation (DBS) therapy for the treatment of Parkinson's Disease (PD) is now a well-established option for some patients. Postoperative standardized programming processes can improve the level of postoperative management and programming, relieve symptoms and improve quality of life. In order to improve the quality of the programming, the experts on DBS and PD in neurology and neurosurgery in China reviewed the relevant literatures and combined their own experiences and developed this expert consensus on the programming of deep brain stimulation in patients with PD in China. This Chinese expert consensus on postoperative programming can standardize and improve postoperative management and programming of DBS for PD.
Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen
2010-10-01
Deep Brain Stimulation for Parkinson's disease is a promising treatment for patients who can no longer be treated satisfactorily with L-dopa. Deep Brain Stimulation is known to relieve motor symptoms of Parkinson's disease and improve quality of life. Focusing on how patients experience life when treated with Deep Brain Stimulation can provide essential information on the process patients go through when receiving a treatment that alters the body and changes the illness trajectory. The aim of this study was to explore and describe the experience of living with Parkinson's disease when treated with Deep Brain Stimulation. The study was designed as a longitudinal study and data were gathered through qualitative in-depth interviews three times during the first year of treatment. Nine patients participated in the study. They were included when they had accepted treatment with Deep Brain Stimulation for Parkinson's disease. Data collection and data analysis were inspired by the hermeneutic phenomenological methodology of Van Manen. The treatment had a major impact on the body. Participants experienced great bodily changes and went through a process of adjustment in three phases during the first year of treatment with Deep Brain Stimulation. These stages were; being liberated: a kind of miracle, changes as a challenge: decline or opportunity and reconciliation: re-defining life with Parkinson's disease. The course of the process was unique for each participant, but dominant was that difficulties during the adjustment of stimulation and medication did affect the re-defining process. Patients go through a dramatic process of change following Deep Brain Stimulation. A changing body affects their entire lifeworld. Some adjust smoothly to changes while others are affected by loss of control, uncertainty and loss of everyday life as they knew it. These experiences affect the process of adjusting to life with Deep Brain Stimulation and re-define life with Parkinson's disease
Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review.
Vázquez-Bourgon, Javier; Martino, Juan; Sierra Peña, María; Infante Ceberio, Jon; Martínez Martínez, M Ángeles; Ocón, Roberto; Menchón, José Manuel; Crespo Facorro, Benedicto; Vázquez-Barquero, Alfonso
2017-07-01
At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit. Copyright
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.
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.
Deep brain stimulation for psychiatric disorders: Is there an impact on social functioning?
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
Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex.
Gjedde, Albert; Geday, Jacob
2009-12-07
We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors.
[Neurological and technical aspects of deep brain stimulation].
Voges, J; Krauss, J K
2010-06-01
Deep brain stimulation (DBS) is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. Despite the functional efficacy of DBS, which in parts is documented on the highest evidence level, the underlying mechanisms are still not completely understood. According to the current state of knowledge electrophysiological and functional data give evidence that high-frequency DBS has an inhibitory effect around the stimulation electrode whilst at the same time axons entering or leaving the stimulated brain area are excited leading to modulation of neuronal networks. The latter effect modifies pathological discharges of neurons in key structures of the basal ganglia network (e.g. irregular bursting activity, oscillations or synchronization) which are found in particular movement disorders such as Parkinson' s disease or dystonia. The introduction of technical standards, such as the integration of high resolution MRI into computer-assisted treatment planning, in combination with special treatment planning software have contributed significantly to the reduction of severe surgical complications (frequency of intracranial hemorrhaging 1-3%) in recent years. Future developments will address the modification of hardware components of the stimulation system, the evaluation of new brain target areas, the simultaneous stimulation of different brain areas and the assessment of different stimulation paradigms (high-frequency vs low-frequency DBS).
Cognitive assessment instruments in Parkinson's disease patients undergoing deep brain stimulation
Romann, Aline Juliane; Dornelles, Silvia; Maineri, Nicole de Liz; Rieder, Carlos Roberto de Mello; Olchik, Maira Rozenfeld
2012-01-01
Deep Brain Stimulation (DBS) is a widely used surgical technique in individuals with Parkinson's disease (PD) that can lead to significant reductions in motor symptoms. Objectives To determine, from publications, the most commonly used instruments for cognitive evaluation of individuals with PD undergoing DBS. Methods A systematic review of the databases: PubMed, Medline, EBECS, Scielo and LILACS was conducted, using the descriptors "Deep Brain Stimulation", "Verbal Fluency", "Parkinson Disease", "Executive Function", "Cognition" and "Cognitive Assessment" in combination. Results The Verbal Fluency test was found to be the most used instrument for this investigation in the studies, followed by the Boston Naming Test. References to the Stroop Test, Trail Making Test, and Rey's Auditory Verbal Learning Test were also found. Conclusions The validation of instruments for this population is needed as is the use of batteries offering greater specificity and sensitivity for the detection of cognitive impairment. PMID:29213766
Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan
2015-01-01
Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869
NASA Technical Reports Server (NTRS)
Mason, B. S.; Pearson, T. J.; Readhead, A. C. S.; Shepherd, M. C.; Sievers, J.; Udomprasert, P. S.; Cartwright, J. K.; Farmer, A. J.; Padin, S.; Myers, S. T.;
2002-01-01
We report measurements of anisotropy in the cosmic microwave background radiation over the multipole range l approximately 200 (right arrow) 3500 with the Cosmic Background Imager based on deep observations of three fields. These results confirm the drop in power with increasing l first reported in earlier measurements with this instrument, and extend the observations of this decline in power out to l approximately 2000. The decline in power is consistent with the predicted damping of primary anisotropies. At larger multipoles, l = 2000-3500, the power is 3.1 sigma greater than standard models for intrinsic microwave background anisotropy in this multipole range, and 3.5 sigma greater than zero. This excess power is not consistent with expected levels of residual radio source contamination but, for sigma 8 is approximately greater than 1, is consistent with predicted levels due to a secondary Sunyaev-Zeldovich anisotropy. Further observations are necessary to confirm the level of this excess and, if confirmed, determine its origin.
Deep ensemble learning of sparse regression models for brain disease diagnosis.
Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang
2017-04-01
Recent studies on brain imaging analysis witnessed the core roles of machine learning techniques in computer-assisted intervention for brain disease diagnosis. Of various machine-learning techniques, sparse regression models have proved their effectiveness in handling high-dimensional data but with a small number of training samples, especially in medical problems. In the meantime, deep learning methods have been making great successes by outperforming the state-of-the-art performances in various applications. In this paper, we propose a novel framework that combines the two conceptually different methods of sparse regression and deep learning for Alzheimer's disease/mild cognitive impairment diagnosis and prognosis. Specifically, we first train multiple sparse regression models, each of which is trained with different values of a regularization control parameter. Thus, our multiple sparse regression models potentially select different feature subsets from the original feature set; thereby they have different powers to predict the response values, i.e., clinical label and clinical scores in our work. By regarding the response values from our sparse regression models as target-level representations, we then build a deep convolutional neural network for clinical decision making, which thus we call 'Deep Ensemble Sparse Regression Network.' To our best knowledge, this is the first work that combines sparse regression models with deep neural network. In our experiments with the ADNI cohort, we validated the effectiveness of the proposed method by achieving the highest diagnostic accuracies in three classification tasks. We also rigorously analyzed our results and compared with the previous studies on the ADNI cohort in the literature. Copyright © 2017 Elsevier B.V. All rights reserved.
Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain
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
Orientation selective deep brain stimulation
NASA Astrophysics Data System (ADS)
Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom
2017-02-01
Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.
Bibliometric profile of deep brain stimulation.
Hu, Kejia; Moses, Ziev B; Xu, Wendong; Williams, Ziv
2017-10-01
We aimed to identify and analyze the characteristics of the 100 most highly-cited papers in the research field of deep brain stimulation (DBS). The Web of Science was searched for highly-cited papers related to DBS research. The number of citations, countries, institutions of origin, year of publication, and research area were noted and analyzed. The 100 most highly-cited articles had a mean of 304.15 citations. These accrued an average of 25.39 citations a year. The most represented target by far was the subthalamic nucleus (STN). These articles were published in 46 high-impact journals, with Brain (n = 10) topping the list. These articles came from 11 countries, with the USA contributing the most highly-cited articles (n = 29); however, it was the University of Toronto (n = 13) in Canada that was the institution with the most highly-cited studies. This study identified the 100 most highly-cited studies and highlighted a historical perspective on the progress in the field of DBS. These findings allow for the recognition of the most influential reports and provide useful information that can indicate areas requiring further investigation.
Sixel-Döring, F; Trenkwalder, C; Kappus, C; Hellwig, D
2006-08-01
Deep brain stimulation of the subthalamic nucleus is an important treatment option for advanced stages of idiopathic Parkinson's disease, leading to significant improvement of motor symptoms in suited patients. Hardware-related complications such as technical malfunction, skin erosion, and infections however cause patient discomfort and additional expense. The patient presented here suffered a putrid infection of the impulse generator site following only local dental treatment of apical parodontitis. Therefore, prophylactic systemic antibiotic treatment is recommended for patients with implanted deep brain stimulation devices in case of operations, dental procedures, or infectious disease.
The Effect of Deep Brain Stimulation on the Speech Motor System
ERIC Educational Resources Information Center
Mücke, Doris; Becker, Johannes; Barbe, Michael T.; Meister, Ingo; Liebhart, Lena; Roettger, Timo B.; Dembek, Till; Timmermann, Lars; Grice, Martine
2014-01-01
Purpose: Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the…
Effect of brain shift on the creation of functional atlases for deep brain stimulation surgery
Pallavaram, Srivatsan; Remple, Michael S.; Neimat, Joseph S.; Kao, Chris; Konrad, Peter E.; D’Haese, Pierre-François
2011-01-01
Purpose In the recent past many groups have tried to build functional atlases of the deep brain using intra-operatively acquired information such as stimulation responses or micro-electrode recordings. An underlying assumption in building such atlases is that anatomical structures do not move between pre-operative imaging and intra-operative recording. In this study, we present evidences that this assumption is not valid. We quantify the effect of brain shift between pre-operative imaging and intra-operative recording on the creation of functional atlases using intra-operative somatotopy recordings and stimulation response data. Methods A total of 73 somatotopy points from 24 bilateral subthalamic nucleus (STN) implantations and 52 eye deviation stimulation response points from 17 bilateral STN implantations were used. These points were spatially normalized on a magnetic resonance imaging (MRI) atlas using a fully automatic non-rigid registration algorithm. Each implantation was categorized as having low, medium or large brain shift based on the amount of pneumocephalus visible on post-operative CT. The locations of somatotopy clusters and stimulation maps were analyzed for each category. Results The centroid of the large brain shift cluster of the somatotopy data (posterior, lateral, inferior: 3.06, 11.27, 5.36 mm) was found posterior, medial and inferior to that of the medium cluster (2.90, 13.57, 4.53 mm) which was posterior, medial and inferior to that of the low shift cluster (1.94, 13.92, 3.20 mm). The coordinates are referenced with respect to the mid-commissural point. Euclidean distances between the centroids were 1.68, 2.44 and 3.59 mm, respectively for low-medium, medium-large and low-large shift clusters. We found similar trends for the positions of the stimulation maps. The Euclidian distance between the highest probability locations on the low and medium-large shift maps was 4.06 mm. Conclusion The effect of brain shift in deep brain stimulation (DBS
Péron, J; Dondaine, T
2012-01-01
The subthalamic nucleus deep-brain stimulation Parkinson's disease patient model seems to represent a unique opportunity for studying the functional role of the basal ganglia and notably the subthalamic nucleus in human emotional processing. Indeed, in addition to constituting a therapeutic advance for severely disabled Parkinson's disease patients, deep brain stimulation is a technique, which selectively modulates the activity of focal structures targeted by surgery. There is growing evidence of a link between emotional impairments and deep-brain stimulation of the subthalamic nucleus. In this context, according to the definition of emotional processing exposed in the companion paper available in this issue, the aim of the present review will consist in providing a synopsis of the studies that investigated the emotional disturbances observed in subthalamic nucleus deep brain stimulation Parkinson's disease patients. This review leads to the conclusion that several emotional components would be disrupted after subthalamic nucleus deep brain stimulation in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. Finally, after a description of the limitations of this study model, we discuss the functional role of the subthalamic nucleus (and the striato-thalamo-cortical circuits in which it is involved) in emotional processing. It seems reasonable to conclude that the striato-thalamo-cortical circuits are indeed involved in emotional processing and that the subthalamic nucleus plays a central in role the human emotional architecture. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
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
Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease
ERIC Educational Resources Information Center
Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh
2011-01-01
Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…
A deep learning model integrating FCNNs and CRFs for brain tumor segmentation.
Zhao, Xiaomei; Wu, Yihong; Song, Guidong; Li, Zhenye; Zhang, Yazhuo; Fan, Yong
2018-01-01
Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis, treatment planning, and treatment outcome evaluation. Build upon successful deep learning techniques, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNNs) and Conditional Random Fields (CRFs) in a unified framework to obtain segmentation results with appearance and spatial consistency. We train a deep learning based segmentation model using 2D image patches and image slices in following steps: 1) training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks (CRF-RNN) using image slices with parameters of FCNNs fixed; and 3) fine-tuning the FCNNs and the CRF-RNN using image slices. Particularly, we train 3 segmentation models using 2D image patches and slices obtained in axial, coronal and sagittal views respectively, and combine them to segment brain tumors using a voting based fusion strategy. Our method could segment brain images slice-by-slice, much faster than those based on image patches. We have evaluated our method based on imaging data provided by the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental results have demonstrated that our method could build a segmentation model with Flair, T1c, and T2 scans and achieve competitive performance as those built with Flair, T1, T1c, and T2 scans. Copyright © 2017 Elsevier B.V. All rights reserved.
Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan
2015-08-01
Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.
Nguyen, Thanh; Bui, Vy; Lam, Van; Raub, Christopher B; Chang, Lin-Ching; Nehmetallah, George
2017-06-26
We propose a fully automatic technique to obtain aberration free quantitative phase imaging in digital holographic microscopy (DHM) based on deep learning. The traditional DHM solves the phase aberration compensation problem by manually detecting the background for quantitative measurement. This would be a drawback in real time implementation and for dynamic processes such as cell migration phenomena. A recent automatic aberration compensation approach using principle component analysis (PCA) in DHM avoids human intervention regardless of the cells' motion. However, it corrects spherical/elliptical aberration only and disregards the higher order aberrations. Traditional image segmentation techniques can be employed to spatially detect cell locations. Ideally, automatic image segmentation techniques make real time measurement possible. However, existing automatic unsupervised segmentation techniques have poor performance when applied to DHM phase images because of aberrations and speckle noise. In this paper, we propose a novel method that combines a supervised deep learning technique with convolutional neural network (CNN) and Zernike polynomial fitting (ZPF). The deep learning CNN is implemented to perform automatic background region detection that allows for ZPF to compute the self-conjugated phase to compensate for most aberrations.
Charron, Odelin; Lallement, Alex; Jarnet, Delphine; Noblet, Vincent; Clavier, Jean-Baptiste; Meyer, Philippe
2018-04-01
Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter <1 cm). As part of these treatments, effective detection and precise segmentation of lesions are imperative. Many methods based on deep-learning approaches have been developed for the automatic segmentation of gliomas, but very little for that of brain metastases. We adapted an existing 3D convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI. Copyright © 2018 Elsevier Ltd. All rights reserved.
Rabins, Peter; Appleby, Brian S; Brandt, Jason; DeLong, Mahlon R; Dunn, Laura B; Gabriëls, Loes; Greenberg, Benjamin D; Haber, Suzanne N; Holtzheimer, Paul E; Mari, Zoltan; Mayberg, Helen S; McCann, Evelyn; Mink, Sallie P; Rasmussen, Steven; Schlaepfer, Thomas E; Vawter, Dorothy E; Vitek, Jerrold L; Walkup, John; Mathews, Debra J H
2009-09-01
A 2-day consensus conference was held to examine scientific and ethical issues in the application of deep brain stimulation for treating mood and behavioral disorders, such as major depression, obsessive-compulsive disorder, and Tourette syndrome. The primary objectives of the conference were to (1) establish consensus among participants about the design of future clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and (2) develop standards for the protection of human subjects participating in such studies. Conference participants identified 16 key points for guiding research in this growing field. The adoption of the described guidelines would help to protect the safety and rights of research subjects who participate in clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and have further potential to benefit other stakeholders in the research process, including clinical researchers and device manufactures. That said, the adoption of the guidelines will require broad and substantial commitment from many of these same stakeholders.
In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)
NASA Astrophysics Data System (ADS)
Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je
2017-01-01
New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.
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
Choi, Ki Sueng; Riva-Posse, Patricio; Gross, Robert E; Mayberg, Helen S
2015-11-01
The clinical utility of monitoring behavioral changes during intraoperative testing of subcallosal cingulate deep brain stimulation is unknown. To characterize the structural connectivity correlates of deep brain stimulation-evoked behavioral effects using probabilistic tractography in depression. Categorization of acute behavioral effects was conducted in 9 adults undergoing deep brain stimulation implantation surgery for chronic treatment-resistant depression in a randomized and blinded testing session at Emory University. Patients were studied from September 1, 2011, through June 30, 2013. Post hoc analyses of the structural tractography patterns mediating distinct categories of evoked behavioral effects were defined, including the best response overall. Data analyses were performed from May 1 through July 1, 2015. Categorization of stimulation-induced transient behavioral effects and delineation of the shared white matter tracts mediating response subtypes. Among the 9 patients, 72 active and 36 sham trials were recorded. The following stereotypical behavior patterns were identified: changes in interoceptive (noted changes in body state in 30 of 72 active and 4 of 36 sham trials) and in exteroceptive (shift in attention from patient to others in 9 of 72 active and 0 sham trials) awareness. The best response was a combination of exteroceptive and interoceptive changes at a single left contact for all 9 patients. Structural connectivity showed that the best response contacts had a pattern of connections to the bilateral ventromedial frontal cortex (via forceps minor and left uncinate fasciculus) and to the cingulate cortex (via left cingulum bundle), whereas behaviorally salient but nonbest contacts had only cingulate involvement. The involvement of the 3 white matter bundles during stimulation of the best contacts suggests a mechanism for the observed transient "depression switch." This analysis of transient behavior changes during intraoperative deep brain
Deep Convolutional Neural Networks for Multi-Modality Isointense Infant Brain Image Segmentation
Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang
2015-01-01
The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multimodality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. PMID:25562829
Deep brain stimulation for phantom limb pain.
Bittar, Richard G; Otero, Sofia; Carter, Helen; Aziz, Tipu Z
2005-05-01
Phantom limb pain is an often severe and debilitating phenomenon that has been reported in up to 85% of amputees. Its pathophysiology is poorly understood. Peripheral and spinal mechanisms are thought to play a role in pain modulation in affected individuals; however central mechanisms are also likely to be of importance. The neuromatrix theory postulates a genetically determined representation of body image, which is modified by sensory input to create a neurosignature. Persistence of the neurosignature may be responsible for painless phantom limb sensations, whereas phantom limb pain may be due to abnormal reorganisation within the neuromatrix. This study assessed the clinical outcome of deep brain stimulation of the periventricular grey matter and somatosensory thalamus for the relief of chronic neuropathic pain associated with phantom limb in three patients. These patients were assessed preoperatively and at 3 month intervals postoperatively. Self-rated visual analogue scale pain scores assessed pain intensity, and the McGill Pain Questionnaire assessed the quality of the pain. Quality of life was assessed using the EUROQOL EQ-5D scale. Periventricular gray stimulation alone was optimal in two patients, whilst a combination of periventricular gray and thalamic stimulation produced the greatest degree of relief in one patient. At follow-up (mean 13.3 months) the intensity of pain was reduced by 62% (range 55-70%). In all three patients, the burning component of the pain was completely alleviated. Opiate intake was reduced in the two patients requiring morphine sulphate pre-operatively. Quality of life measures indicated a statistically significant improvement. This data supports the role for deep brain stimulation in patients with phantom limb pain. The medical literature relating to the epidemiology, pathogenesis, and treatment of this clinical entity is reviewed in detail.
Deep brain transcranial magnetic stimulation using variable "Halo coil" system
NASA Astrophysics Data System (ADS)
Meng, Y.; Hadimani, R. L.; Crowther, L. J.; Xu, Z.; Qu, J.; Jiles, D. C.
2015-05-01
Transcranial Magnetic Stimulation has the potential to treat various neurological disorders non-invasively and safely. The "Halo coil" configuration can stimulate deeper regions of the brain with lower surface to deep-brain field ratio compared to other coil configurations. The existing "Halo coil" configuration is fixed and is limited in varying the site of stimulation in the brain. We have developed a new system based on the current "Halo coil" design along with a graphical user interface system that enables the larger coil to rotate along the transverse plane. The new system can also enable vertical movement of larger coil. Thus, this adjustable "Halo coil" configuration can stimulate different regions of the brain by adjusting the position and orientation of the larger coil on the head. We have calculated magnetic and electric fields inside a MRI-derived heterogeneous head model for various positions and orientations of the coil. We have also investigated the mechanical and thermal stability of the adjustable "Halo coil" configuration for various positions and orientations of the coil to ensure safe operation of the system.
Deep Brain Stimulation of the Memory Circuit: Improving Cognition in Alzheimer's Disease.
Posporelis, Sotirios; David, Anthony S; Ashkan, Keyoumars; Shotbolt, Paul
2018-05-26
Deep brain stimulation (DBS) is an effective invasive treatment for a wide range of neurological and psychiatric disorders. Neurosurgically implanted electrodes deliver stimulation of pre-programmed amplitude, frequency, and pulse width within deep brain structures; those settings can be adjusted at a later stage according to individual needs for optimal response. This results in variable effects dependent on the targeted region. An established treatment for movement disorders, the effectiveness of DBS in dementia remains under investigation. Translational studies have uncovered a pro-cognitive effect mediated by changes on cellular as well as network level. Several groups have attempted to examine the benefits of DBS in Alzheimer's disease; differences in inclusion criteria and methodology make generalization of results difficult. This review aims to summarize all completed and ongoing human studies of DBS in Alzheimer's disease. The results are classified by targeted anatomical structure. Future directions, as well as economical and ethical arguments, are explored in the final section.
Technical nuances to minimize common complications of deep brain stimulation.
House, Paul
2017-04-01
The implantation of deep brain stimulator electrodes is associated with infrequent complications. These complications are consistent across prospective trials and include infection, skin erosion, hemorrhage, and lead misplacement. Nuances of surgical technique can be used to minimize the risk of these commonly noted complications. Several of these technical nuances are highlighted in this video submission. The video can be found here: https://youtu.be/GL09W9p013g .
NASA Astrophysics Data System (ADS)
DePaoli, Damon T.; Lapointe, Nicolas; Goetz, Laurent; Parent, Martin; Prudhomme, Michel; Cantin, Léo.; Galstian, Tigran; Messaddeq, Younès.; Côté, Daniel C.
2016-03-01
Deep brain stimulation's effectiveness relies on the ability of the stimulating electrode to be properly placed within a specific target area of the brain. Optical guidance techniques that can increase the accuracy of the procedure, without causing any additional harm, are therefore of great interest. We have designed a cheap optical fiber-based device that is small enough to be placed within commercially available DBS stimulating electrodes' hollow cores and that is capable of sensing biological information from the surrounding tissue, using low power white light. With this probe we have shown the ability to distinguish white and grey matter as well as blood vessels, in vitro, in human brain samples and in vivo, in rats. We have also repeated the in vitro procedure with the probe inserted in a DBS stimulating electrode and found the results were in good agreement. We are currently validating a second fiber optic device, with micro-optical components, that will result in label free, molecular level sensing capabilities, using CARS spectroscopy. The final objective will be to use this data in real time, during deep brain stimulation neurosurgery, to increase the safety and accuracy of the procedure.
Adaptive deep brain stimulation in advanced Parkinson disease.
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.
Learning implicit brain MRI manifolds with deep learning
NASA Astrophysics Data System (ADS)
Bermudez, Camilo; Plassard, Andrew J.; Davis, Larry T.; Newton, Allen T.; Resnick, Susan M.; Landman, Bennett A.
2018-03-01
An important task in image processing and neuroimaging is to extract quantitative information from the acquired images in order to make observations about the presence of disease or markers of development in populations. Having a low-dimensional manifold of an image allows for easier statistical comparisons between groups and the synthesis of group representatives. Previous studies have sought to identify the best mapping of brain MRI to a low-dimensional manifold, but have been limited by assumptions of explicit similarity measures. In this work, we use deep learning techniques to investigate implicit manifolds of normal brains and generate new, high-quality images. We explore implicit manifolds by addressing the problems of image synthesis and image denoising as important tools in manifold learning. First, we propose the unsupervised synthesis of T1-weighted brain MRI using a Generative Adversarial Network (GAN) by learning from 528 examples of 2D axial slices of brain MRI. Synthesized images were first shown to be unique by performing a cross-correlation with the training set. Real and synthesized images were then assessed in a blinded manner by two imaging experts providing an image quality score of 1-5. The quality score of the synthetic image showed substantial overlap with that of the real images. Moreover, we use an autoencoder with skip connections for image denoising, showing that the proposed method results in higher PSNR than FSL SUSAN after denoising. This work shows the power of artificial networks to synthesize realistic imaging data, which can be used to improve image processing techniques and provide a quantitative framework to structural changes in the brain.
Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasound
Darvas, F; Mehić, E; Caler, CJ; Ojemann, JG; Mourad, PD
2017-01-01
Noninvasive recordings of electrophysiological activity have limited anatomical specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalogram (EEG) signal induced by pulsed focused ultrasound (pFU) could overcome those limitations. As a first step towards testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200 microsecond-long pulses applied at 1050 Hz for one second at a spatial peak temporal average intensity of 1.4 W/cm2) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050 Hz electrophysiological signal only when ultrasound was applied to living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pFU as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID:27181686
Sillay, Karl A.; Kumbier, L. M.; Ross, C.; Brady, M.; Alexander, A.; Gupta, A.; Adluru, N.; Miranpuri, G. S.; Williams, J. C.
2016-01-01
Deep brain stimulation (DBS) efficacy is related to optimal electrode placement. Several authors have quantified brain shift related to surgical targeting; yet, few reports document and discuss the effects of brain shift after insertion. Objective: To quantify brain shift and electrode displacement after device insertion. Twelve patients were retrospectively reviewed, and one post-operative MRI and one time-delayed CT were obtained for each patient and their implanted electrodes modeled in 3D. Two competing methods were employed to measure the electrode tip location and deviation from the prototypical linear implant after the resolution of acute surgical changes, such as brain shift and pneumocephalus. In the interim between surgery and a pneumocephalus free postoperative scan, electrode deviation was documented in all patients and all electrodes. Significant shift of the electrode tip was identified in rostral, anterior, and medial directions (p < 0.05). Shift was greatest in the rostral direction, measuring an average of 1.41 mm. Brain shift and subsequent electrode displacement occurs in patients after DBS surgery with the reversal of intraoperative brain shift. Rostral displacement is on the order of the height of one DBS contact. Further investigation into the time course of intraoperative brain shift and its potential effects on procedures performed with rigid and non-rigid devices in supine and semi-sitting surgical positions is needed. PMID:23010803
Kruit, Mark C.; Launer, Lenore J.; Overbosch, Jelle; van Buchem, Mark A.; Ferrari, Michel D.
2011-01-01
Background A small MRI study showed increased iron depositions in the periaqueductal grey matter in migraineurs, suggestive of a disturbed central antinociceptive neuronal network. Procedures With 1.5T MRI, we assessed iron concentrations in seven deep brain nuclei in a large population-based cohort. We compared T2 values between migraineurs (n=138) and controls (n=75), with multivariate regression analysis. Analyses were conducted in age strata (<50, n=112; ≥50) because iron measures are increasingly influenced by non-iron related factors in the older group. Findings Overall, migraineurs and controls did not differ, nor did migraineurs with vs. without aura. In the younger migraineurs compared to controls, T2-values were lower in the putamen (p=0.02), globus pallidus (p=0.03) and red nucleus (p=0.03). Similarly, in these younger migraineurs, controlling for age, those with longer migraine-history had lower T2 values in the putamen (p=0.01), caudate (p=0.04) and red nucleus (p=0.001). Conclusions Repeated migraine attacks are associated with increased iron concentration / accumulation in multiple deep nuclei that are involved in central pain processing and migraine pathophysiology. It remains unclear whether iron accumulation in the antinociceptive network has a causative role in the development of (chronic) migraine headache. PMID:19025553
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.
The effect of deep brain stimulation on the speech motor system.
Mücke, Doris; Becker, Johannes; Barbe, Michael T; Meister, Ingo; Liebhart, Lena; Roettger, Timo B; Dembek, Till; Timmermann, Lars; Grice, Martine
2014-08-01
Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the coordination of oral and glottal articulation. Sixteen native-speaking German adults with essential tremor, between 26 and 86 years old, with and without chronic deep brain stimulation of the nucleus ventralis intermedius and 12 healthy, age-matched subjects were recorded performing a fast syllable repetition task (/papapa/, /tatata/, /kakaka/). Syllable duration and voicing-to-syllable ratio as well as parameters related directly to consonant production, voicing during constriction, and frication during constriction were measured. Voicing during constriction was greater in subjects with essential tremor than in controls, indicating a perseveration of voicing into the voiceless consonant. Stimulation led to fewer voiceless intervals (voicing-to-syllable ratio), indicating a reduced degree of glottal abduction during the entire syllable cycle. Stimulation also induced incomplete oral closures (frication during constriction), indicating imprecise oral articulation. The detrimental effect of stimulation on the speech motor system can be quantified using acoustic measures at the subsyllabic level.
Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E
2012-01-01
Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.
Current Topics in Deep Brain Stimulation for Parkinson Disease
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
Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine
2017-07-01
In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.
Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Østergaard, Karen
2013-02-01
This article is a report of an exploration of the lived experience of being a spouse to a person living with advanced Parkinson's disease, before and during the first year of deep brain stimulation. Parkinson's disease is a chronic progressive neurodegenerative disease. It has a profound impact on the everyday life for patients and spouses. Deep brain stimulation is offered with the aim of reducing symptoms of Parkinson's disease. The treatment is known to improve quality of life for patients, but little is known of how spouses experience life following their partners' treatment. A longitudinal interview study with a hermeneutic phenomenological approach. Ten spouses were included in the study. Data were gathered in 2007-2008, through qualitative in-depth interviews with spouses once before and three times during the first year of their partners' treatment with Deep Brain Stimulation. Data collection and data analysis were influenced by the hermeneutic phenomenological methodology of van Manen. The uniting theme 'Solidarity - the base for joined responsibility and concern' was the foundation for the relationship between spouses and their partners. Before treatment, the theme 'Living in partnership' was dominant. After treatment two dichotomous courses were described 'A sense of freedom embracing life' and 'The challenge of changes and constraint'. Spouses are deeply involved in their partners' illness and their experience of life is highly affected by their partners' illness, both before and after deep brain stimulation. The relationship is founded on solidarity and responsibility, which emphasizes spouses' need to be informed and involved in the process following Deep Brain Stimulation. © 2012 Blackwell Publishing Ltd.
ERIC Educational Resources Information Center
Mahoney, Rachel; Selway, Richard; Lin, Jean-Pierre
2011-01-01
Aim: To examine the cognitive functioning of young people with pantothenate-kinase-associated neurodegeneration (PKAN) after pallidal deep brain stimulation (DBS). PKAN is characterized by progressive generalized dystonia and has historically been associated with cognitive decline. With growing evidence that DBS can improve motor function in…
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
A PC-based system for predicting movement from deep brain signals in Parkinson's disease.
Loukas, Constantinos; Brown, Peter
2012-07-01
There is much current interest in deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of Parkinson's disease (PD). This type of surgery has enabled unprecedented access to deep brain signals in the awake human. In this paper we present an easy-to-use computer based system for recording, displaying, archiving, and processing electrophysiological signals from the STN. The system was developed for predicting self-paced hand-movements in real-time via the online processing of the electrophysiological activity of the STN. It is hoped that such a computerised system might have clinical and experimental applications. For example, those sites within the STN most relevant to the processing of voluntary movement could be identified through the predictive value of their activities with respect to the timing of future movement. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Update on Deep Brain Stimulation for Dyskinesia and Dystonia: A Literature Review
TODA, Hiroki; SAIKI, Hidemoto; NISHIDA, Namiko; IWASAKI, Koichi
2016-01-01
Deep brain stimulation (DBS) has been an established surgical treatment option for dyskinesia from Parkinson disease and for dystonia. The present article deals with the timing of surgical intervention, selecting an appropriate target, and minimizing adverse effects. We provide an overview of current evidences and issues for dyskinesia and dystonia as well as emerging DBS technology. PMID:27053331
Thalamic Deep Brain Stimulation for Writer's Cramp.
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.
Bohme, Andrea; van Rienen, Ursula
2016-08-01
Computational modeling of the stimulating field distribution during Deep Brain Stimulation provides an opportunity to advance our knowledge of this neurosurgical therapy for Parkinson's disease. There exist several approaches to model the target region for Deep Brain Stimulation in Hemi-parkinson Rats with volume conductor models. We have described and compared the normalized mapping approach as well as the modeling with three-dimensional structures, which include curvilinear coordinates to assure an anatomically realistic conductivity tensor orientation.
Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease
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
Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.
Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S
2012-09-01
Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.
Chiarelli, Antonio Maria; Croce, Pierpaolo; Merla, Arcangelo; Zappasodi, Filippo
2018-06-01
Brain-computer interface (BCI) refers to procedures that link the central nervous system to a device. BCI was historically performed using electroencephalography (EEG). In the last years, encouraging results were obtained by combining EEG with other neuroimaging technologies, such as functional near infrared spectroscopy (fNIRS). A crucial step of BCI is brain state classification from recorded signal features. Deep artificial neural networks (DNNs) recently reached unprecedented complex classification outcomes. These performances were achieved through increased computational power, efficient learning algorithms, valuable activation functions, and restricted or back-fed neurons connections. By expecting significant overall BCI performances, we investigated the capabilities of combining EEG and fNIRS recordings with state-of-the-art deep learning procedures. We performed a guided left and right hand motor imagery task on 15 subjects with a fixed classification response time of 1 s and overall experiment length of 10 min. Left versus right classification accuracy of a DNN in the multi-modal recording modality was estimated and it was compared to standalone EEG and fNIRS and other classifiers. At a group level we obtained significant increase in performance when considering multi-modal recordings and DNN classifier with synergistic effect. BCI performances can be significantly improved by employing multi-modal recordings that provide electrical and hemodynamic brain activity information, in combination with advanced non-linear deep learning classification procedures.
Deep brain optical measurements of cell type-specific neural activity in behaving mice.
Cui, Guohong; Jun, Sang Beom; Jin, Xin; Luo, Guoxiang; Pham, Michael D; Lovinger, David M; Vogel, Steven S; Costa, Rui M
2014-01-01
Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (TCSPC)-based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with Cre-dependent selective expression of genetically encoded Ca(2+) indicators (GECIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. As an example, we used viral expression of GCaMPs in striatal projection neurons (SPNs) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. The whole procedure, consisting of virus injection, behavior training and optical recording, takes 3-4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. The simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior.
Stimulating at the right time: phase-specific deep brain stimulation.
Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter
2017-01-01
SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.
Ekmekci, Hakan; Kaptan, Hulagu
2016-01-01
Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.
Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics
NASA Astrophysics Data System (ADS)
Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.
2018-01-01
The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.
Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain
Shirvalkar, Prasad; Veuthey, Tess L.; Dawes, Heather E.; Chang, Edward F.
2018-01-01
Pain is a subjective experience that alerts an individual to actual or potential tissue damage. Through mechanisms that are still unclear, normal physiological pain can lose its adaptive value and evolve into pathological chronic neuropathic pain. Chronic pain is a multifaceted experience that can be understood in terms of somatosensory, affective, and cognitive dimensions, each with associated symptoms and neural signals. While there have been many attempts to treat chronic pain, in this article we will argue that feedback-controlled ‘closed-loop’ deep brain stimulation (DBS) offers an urgent and promising route for treatment. Contemporary DBS trials for chronic pain use “open-loop” approaches in which tonic stimulation is delivered with fixed parameters to a single brain region. The impact of key variables such as the target brain region and the stimulation waveform is unclear, and long-term efficacy has mixed results. We hypothesize that chronic pain is due to abnormal synchronization between brain networks encoding the somatosensory, affective and cognitive dimensions of pain, and that multisite, closed-loop DBS provides an intuitive mechanism for disrupting that synchrony. By (1) identifying biomarkers of the subjective pain experience and (2) integrating these signals into a state-space representation of pain, we can create a predictive model of each patient's pain experience. Then, by establishing how stimulation in different brain regions influences individual neural signals, we can design real-time, closed-loop therapies tailored to each patient. While chronic pain is a complex disorder that has eluded modern therapies, rich historical data and state-of-the-art technology can now be used to develop a promising treatment. PMID:29632482
Islam, Jyoti; Zhang, Yanqing
2018-05-31
Alzheimer's disease is an incurable, progressive neurological brain disorder. Earlier detection of Alzheimer's disease can help with proper treatment and prevent brain tissue damage. Several statistical and machine learning models have been exploited by researchers for Alzheimer's disease diagnosis. Analyzing magnetic resonance imaging (MRI) is a common practice for Alzheimer's disease diagnosis in clinical research. Detection of Alzheimer's disease is exacting due to the similarity in Alzheimer's disease MRI data and standard healthy MRI data of older people. Recently, advanced deep learning techniques have successfully demonstrated human-level performance in numerous fields including medical image analysis. We propose a deep convolutional neural network for Alzheimer's disease diagnosis using brain MRI data analysis. While most of the existing approaches perform binary classification, our model can identify different stages of Alzheimer's disease and obtains superior performance for early-stage diagnosis. We conducted ample experiments to demonstrate that our proposed model outperformed comparative baselines on the Open Access Series of Imaging Studies dataset.
Deep brain two-photon NIR fluorescence imaging for study of Alzheimer's disease
NASA Astrophysics Data System (ADS)
Chen, Congping; Liang, Zhuoyi; Zhou, Biao; Ip, Nancy Y.; Qu, Jianan Y.
2018-02-01
Amyloid depositions in the brain represent the characteristic hallmarks of Alzheimer's disease (AD) pathology. The abnormal accumulation of extracellular amyloid-beta (Aβ) and resulting toxic amyloid plaques are considered to be responsible for the clinical deficits including cognitive decline and memory loss. In vivo two-photon fluorescence imaging of amyloid plaques in live AD mouse model through a chronic imaging window (thinned skull or craniotomy) provides a mean to greatly facilitate the study of the pathological mechanism of AD owing to its high spatial resolution and long-term continuous monitoring. However, the imaging depth for amyloid plaques is largely limited to upper cortical layers due to the short-wavelength fluorescence emission of commonly used amyloid probes. In this work, we reported that CRANAD-3, a near-infrared (NIR) probe for amyloid species with excitation wavelength at 900 nm and emission wavelength around 650 nm, has great advantages over conventionally used probes and is well suited for twophoton deep imaging of amyloid plaques in AD mouse brain. Compared with a commonly used MeO-X04 probe, the imaging depth of CRANAD-3 is largely extended for open skull cranial window. Furthermore, by using two-photon excited fluorescence spectroscopic imaging, we characterized the intrinsic fluorescence of the "aging pigment" lipofuscin in vivo, which has distinct spectra from CRANAD-3 labeled plaques. This study reveals the unique potential of NIR probes for in vivo, high-resolution and deep imaging of brain amyloid in Alzheimer's disease.
Dynamic Neural State Identification in Deep Brain Local Field Potentials of Neuropathic Pain.
Luo, Huichun; Huang, Yongzhi; Du, Xueying; Zhang, Yunpeng; Green, Alexander L; Aziz, Tipu Z; Wang, Shouyan
2018-01-01
In neuropathic pain, the neurophysiological and neuropathological function of the ventro-posterolateral nucleus of the thalamus (VPL) and the periventricular gray/periaqueductal gray area (PVAG) involves multiple frequency oscillations. Moreover, oscillations related to pain perception and modulation change dynamically over time. Fluctuations in these neural oscillations reflect the dynamic neural states of the nucleus. In this study, an approach to classifying the synchronization level was developed to dynamically identify the neural states. An oscillation extraction model based on windowed wavelet packet transform was designed to characterize the activity level of oscillations. The wavelet packet coefficients sparsely represented the activity level of theta and alpha oscillations in local field potentials (LFPs). Then, a state discrimination model was designed to calculate an adaptive threshold to determine the activity level of oscillations. Finally, the neural state was represented by the activity levels of both theta and alpha oscillations. The relationship between neural states and pain relief was further evaluated. The performance of the state identification approach achieved sensitivity and specificity beyond 80% in simulation signals. Neural states of the PVAG and VPL were dynamically identified from LFPs of neuropathic pain patients. The occurrence of neural states based on theta and alpha oscillations were correlated to the degree of pain relief by deep brain stimulation. In the PVAG LFPs, the occurrence of the state with high activity levels of theta oscillations independent of alpha and the state with low-level alpha and high-level theta oscillations were significantly correlated with pain relief by deep brain stimulation. This study provides a reliable approach to identifying the dynamic neural states in LFPs with a low signal-to-noise ratio by using sparse representation based on wavelet packet transform. Furthermore, it may advance closed-loop deep
Dynamic Neural State Identification in Deep Brain Local Field Potentials of Neuropathic Pain
Luo, Huichun; Huang, Yongzhi; Du, Xueying; Zhang, Yunpeng; Green, Alexander L.; Aziz, Tipu Z.; Wang, Shouyan
2018-01-01
In neuropathic pain, the neurophysiological and neuropathological function of the ventro-posterolateral nucleus of the thalamus (VPL) and the periventricular gray/periaqueductal gray area (PVAG) involves multiple frequency oscillations. Moreover, oscillations related to pain perception and modulation change dynamically over time. Fluctuations in these neural oscillations reflect the dynamic neural states of the nucleus. In this study, an approach to classifying the synchronization level was developed to dynamically identify the neural states. An oscillation extraction model based on windowed wavelet packet transform was designed to characterize the activity level of oscillations. The wavelet packet coefficients sparsely represented the activity level of theta and alpha oscillations in local field potentials (LFPs). Then, a state discrimination model was designed to calculate an adaptive threshold to determine the activity level of oscillations. Finally, the neural state was represented by the activity levels of both theta and alpha oscillations. The relationship between neural states and pain relief was further evaluated. The performance of the state identification approach achieved sensitivity and specificity beyond 80% in simulation signals. Neural states of the PVAG and VPL were dynamically identified from LFPs of neuropathic pain patients. The occurrence of neural states based on theta and alpha oscillations were correlated to the degree of pain relief by deep brain stimulation. In the PVAG LFPs, the occurrence of the state with high activity levels of theta oscillations independent of alpha and the state with low-level alpha and high-level theta oscillations were significantly correlated with pain relief by deep brain stimulation. This study provides a reliable approach to identifying the dynamic neural states in LFPs with a low signal-to-noise ratio by using sparse representation based on wavelet packet transform. Furthermore, it may advance closed-loop deep
Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.
Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg
2018-02-13
There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly
Chou, Kelvin L; Taylor, Jennifer L; Patil, Parag G
2013-11-01
The Movement Disorders Society revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) improves upon the original UPDRS by adding more non-motor items, making it a more robust tool to evaluate the severity of motor and non-motor symptoms of Parkinson disease. Previous studies on deep brain stimulation have not used the MDS-UPDRS. To determine if the MDS-UPDRS could detect improvement in both motor and non-motor symptoms after bilateral subthalamic nucleus deep brain stimulation for Parkinson disease. We compared scores on the entire MDS-UPDRS prior to surgery (baseline) and approximately six months following the initial programming visit in twenty subjects (12M/8F) with Parkinson disease undergoing bilateral subthalamic nucleus deep brain stimulation. STN DBS significantly improved the scores for every section of the MDS-UPDRS at the 6 month follow-up. Part I improved by 3.1 points (22%), Part II by 5.3 points (29%), Part III by 13.1 points (29%) with stimulation alone, and Part IV by 7.1 points (74%). Individual non-motor items in Part I that improved significantly were constipation, light-headedness, and fatigue. Both motor and non-motor symptoms, as assessed by the MDS-UPDRS, improve with bilateral subthalamic nucleus stimulation six months after the stimulator is turned on. We recommend that the MDS-UPDRS be utilized in future deep brain stimulation studies because of the advantage of detecting change in non-motor symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.
Encoding-related brain activity during deep processing of verbal materials: a PET study.
Fujii, Toshikatsu; Okuda, Jiro; Tsukiura, Takashi; Ohtake, Hiroya; Suzuki, Maki; Kawashima, Ryuta; Itoh, Masatoshi; Fukuda, Hiroshi; Yamadori, Atsushi
2002-12-01
The recent advent of neuroimaging techniques provides an opportunity to examine brain regions related to a specific memory process such as episodic memory encoding. There is, however, a possibility that areas active during an assumed episodic memory encoding task, compared with a control task, involve not only areas directly relevant to episodic memory encoding processes but also areas associated with other cognitive processes for on-line information. We used positron emission tomography (PET) to differentiate these two kinds of regions. Normal volunteers were engaged in deep (semantic) or shallow (phonological) processing of new or repeated words during PET. Results showed that deep processing, compared with shallow processing, resulted in significantly better recognition performance and that this effect was associated with activation of various brain areas. Further analyses revealed that there were regions directly relevant to episodic memory encoding in the anterior part of the parahippocampal gyrus, inferior frontal gyrus, supramarginal gyrus, anterior cingulate gyrus, and medial frontal lobe in the left hemisphere. Our results demonstrated that several regions, including the medial temporal lobe, play a role in episodic memory encoding.
Hauptmann, C; Roulet, J-C; Niederhauser, J J; Döll, W; Kirlangic, M E; Lysyansky, B; Krachkovskyi, V; Bhatti, M A; Barnikol, U B; Sasse, L; Bührle, C P; Speckmann, E-J; Götz, M; Sturm, V; Freund, H-J; Schnell, U; Tass, P A
2009-12-01
In the past decade deep brain stimulation (DBS)-the application of electrical stimulation to specific target structures via implanted depth electrodes-has become the standard treatment for medically refractory Parkinson's disease and essential tremor. These diseases are characterized by pathological synchronized neuronal activity in particular brain areas. We present an external trial DBS device capable of administering effectively desynchronizing stimulation techniques developed with methods from nonlinear dynamics and statistical physics according to a model-based approach. These techniques exploit either stochastic phase resetting principles or complex delayed-feedback mechanisms. We explain how these methods are implemented into a safe and user-friendly device.
Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor.
Lehn, Alexander C; O'Gorman, Cullen; Olson, Sarah; Salari, Mehri
2017-01-01
Orthostatic tremor (OT) was first described in 1977. It is characterized by rapid tremor of 13-18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS). We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation. Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data.
VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR images.
Chen, Hao; Dou, Qi; Yu, Lequan; Qin, Jing; Heng, Pheng-Ann
2018-04-15
Segmentation of key brain tissues from 3D medical images is of great significance for brain disease diagnosis, progression assessment and monitoring of neurologic conditions. While manual segmentation is time-consuming, laborious, and subjective, automated segmentation is quite challenging due to the complicated anatomical environment of brain and the large variations of brain tissues. We propose a novel voxelwise residual network (VoxResNet) with a set of effective training schemes to cope with this challenging problem. The main merit of residual learning is that it can alleviate the degradation problem when training a deep network so that the performance gains achieved by increasing the network depth can be fully leveraged. With this technique, our VoxResNet is built with 25 layers, and hence can generate more representative features to deal with the large variations of brain tissues than its rivals using hand-crafted features or shallower networks. In order to effectively train such a deep network with limited training data for brain segmentation, we seamlessly integrate multi-modality and multi-level contextual information into our network, so that the complementary information of different modalities can be harnessed and features of different scales can be exploited. Furthermore, an auto-context version of the VoxResNet is proposed by combining the low-level image appearance features, implicit shape information, and high-level context together for further improving the segmentation performance. Extensive experiments on the well-known benchmark (i.e., MRBrainS) of brain segmentation from 3D magnetic resonance (MR) images corroborated the efficacy of the proposed VoxResNet. Our method achieved the first place in the challenge out of 37 competitors including several state-of-the-art brain segmentation methods. Our method is inherently general and can be readily applied as a powerful tool to many brain-related studies, where accurate segmentation of brain
Asleep Deep Brain Stimulation Reduces Incidence of Intracranial Air during Electrode Implantation.
Ko, Andrew L; Magown, Philippe; Ozpinar, Alp; Hamzaoglu, Vural; Burchiel, Kim J
2018-05-30
Asleep deep brain stimulation (aDBS) implantation replaces microelectrode recording for image-guided implantation, shortening the operative time and reducing cerebrospinal fluid egress. This may decrease pneumocephalus, thus decreasing brain shift during implantation. To compare the incidence and volume of pneumocephalus during awake (wkDBS) and aDBS procedures. A retrospective review of bilateral DBS cases performed at Oregon Health & Science University from 2009 to 2017 was undertaken. Postimplantation imaging was reviewed to determine the presence and volume of intracranial air and measure cortical brain shift. Among 371 patients, pneumocephalus was noted in 66% of wkDBS and 15.6% of aDBS. The average volume of air was significantly higher in wkDBS than aDBS (8.0 vs. 1.8 mL). Volumes of air greater than 7 mL, which have previously been linked to brain shift, occurred significantly more frequently in wkDBS than aDBS (34 vs 5.6%). wkDBS resulted in significantly larger cortical brain shifts (5.8 vs. 1.2 mm). We show that aDBS reduces the incidence of intracranial air, larger air volumes, and cortical brain shift. Large volumes of intracranial air have been correlated to shifting of brain structures during DBS procedures, a variable that could impact accuracy of electrode placement. © 2018 S. Karger AG, Basel.
Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation
Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.
2017-01-01
High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176
Stimulating at the right time: phase-specific deep brain stimulation
Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter
2017-01-01
Abstract See Moll and Engel (doi:10.1093/aww308) for a scientific commentary on this article. Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson’s disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient’s tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. PMID:28007997
Deep brain stimulation to reduce sexual drive.
Fuss, Johannes; Auer, Matthias K; Biedermann, Sarah V; Briken, Peer; Hacke, Werner
2015-11-01
To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach.
Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers
Thorbergsson, Palmi Thor; Ekstrand, Joakim; Friberg, Annika; Granmo, Marcus; Pettersson, Lina M. E.; Schouenborg, Jens
2016-01-01
Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved. PMID:27159159
NASA Astrophysics Data System (ADS)
Datteri, Ryan; Pallavaram, Srivatsan; Konrad, Peter E.; Neimat, Joseph S.; D'Haese, Pierre-François; Dawant, Benoit M.
2011-03-01
A number of groups have reported on the occurrence of intra-operative brain shift during deep brain stimulation (DBS) surgery. This has a number of implications for the procedure including an increased chance of intra-cranial bleeding and complications due to the need for more exploratory electrodes to account for the brain shift. It has been reported that the amount of pneumocephalus or air invasion into the cranial cavity due to the opening of the dura correlates with intraoperative brain shift. Therefore, pre-operatively predicting the amount of pneumocephalus expected during surgery is of interest toward accounting for brain shift. In this study, we used 64 DBS patients who received bilateral electrode implantations and had a post-operative CT scan acquired immediately after surgery (CT-PI). For each patient, the volumes of the pneumocephalus, left ventricle, right ventricle, third ventricle, white matter, grey matter, and cerebral spinal fluid were calculated. The pneumocephalus was calculated from the CT-PI utilizing a region growing technique that was initialized with an atlas-based image registration method. A multi-atlas-based image segmentation method was used to segment out the ventricles of each patient. The Statistical Parametric Mapping (SPM) software package was utilized to calculate the volumes of the cerebral spinal fluid (CSF), white matter and grey matter. The volume of individual structures had a moderate correlation with pneumocephalus. Utilizing a multi-linear regression between the volume of the pneumocephalus and the statistically relevant individual structures a Pearson's coefficient of r = 0.4123 (p = 0.0103) was found. This study shows preliminary results that could be used to develop a method to predict the amount of pneumocephalus ahead of the surgery.
Fan, Quli; Cheng, Kai; Yang, Zhen; ...
2014-11-06
In order to promote preclinical and clinical applications of photoacoustic imaging, novel photoacoustic contrast agents are highly desired for molecular imaging of diseases, especially for deep tumor imaging. In this paper, perylene-3,4,9,10-tetracarboxylic diiimide-based near-infrared-absorptive organic nanoparticles are reported as an efficient agent for photoacoustic imaging of deep brain tumors in living mice with enhanced permeability and retention effect
Ramdhani, Ritesh A.; Frucht, Steven J.; Behnegar, Anousheh; Kopell, Brian H.
2016-01-01
Background Myoclonus–dystonia is a condition that manifests predominantly as myoclonic jerks with focal dystonia. It is genetically heterogeneous with most mutations in the epsilon sarcoglycan gene (SGCE). In medically refractory cases, deep brain stimulation (DBS) has been shown to provide marked sustainable clinical improvement, especially in SGCE-positive patients. We present two patients with myoclonus–dystonia (one SGCE positive and the other SGCE negative) who have the isolated myoclonus phenotype and had DBS leads implanted in the bilateral globus pallidus internus (GPi). Methods We review their longitudinal Unified Myoclonus Rating Scale scores along with their DBS programming parameters and compare them with published cases in the literature. Results Both patients demonstrated complete amelioration of all aspects of myoclonus within 6–12 months after surgery. The patient with the SGCE-negative mutation responded just as well as the patient who was SGCE positive. High-frequency stimulation (130 Hz) with amplitudes greater than 2.5 V provided therapeutic benefit. Discussion This case series demonstrates that high frequency GPi-DBS is effective in treating isolated myoclonus in myoclonus–dystonia, regardless of the presence of SGCE mutation. PMID:26989574
Servello, Domenico; Zekaj, Edvin; Saleh, Christian; Pacchetti, Claudio; Porta, Mauro
2016-01-01
Background: Deep brain stimulation (DBS) is an established therapy for movement disorders, such as Parkinson's disease (PD), dystonia, and tremor. The efficacy of DBS depends on the correct lead positioning. The commonly adopted postoperative radiological evaluation is performed with computed tomography (CT) scan and/or magnetic resonance imaging (MRI). Methods: We conducted a retrospective study on 202 patients who underwent DBS from January 2009 to October 2013. DBS indications were PD, progressive supranuclear palsy, tremor, dystonia, Tourette syndrome, obsessive compulsive disorder, depression, and Huntington's disease. Preoperatively, all patients underwent brain MRI and brain CT scan with the stereotactic frame positioned. The lead location was confirmed intraoperatively with CT. The CT images were subsequently transferred to the Stealth Station Medtronic and merged with the preoperative planning. On the first or second day after, implantation we performed a brain MRI to confirm the correct position of the lead. Results: In 14 patients, leads were in suboptimal position after intraoperative CT scan positioning. The cases with alteration in the Z-axis were corrected immediately under fluoroscopic guidance. In all the 14 patients, an immediate repositioning was done. Conclusions: Based on our data, intraoperative CT scan is fast, safe, and a useful tool in the evaluation of the position of the implanted lead. It also reduces the patient's discomfort derived from the transfer of the patient from the operating room to the radiological department. However, intraoperative CT should not be considered as a substitute for postoperative MRI. PMID:27583182
Deep-brain stimulation for aggressive and disruptive behavior.
Franzini, Angelo; Broggi, Giovanni; Cordella, Roberto; Dones, Ivano; Messina, Giuseppe
2013-01-01
To describe our institutional experience with deep-brain stimulation (DBS) used in the treatment of aggressive and disruptive behavior refractory to conservative treatment. With stereotactic methodology and under general anesthesia, seven patients (from 2002 to 2010) were given DBS in the posterior hypothalamic region, bilaterally, and with the aid of intraoperative microrecording. Six of seven patients presented a clear reduction in the aggression and disruptive bouts, with subsequent simplification of familiar management. DBS of the posterior hypothalamic region could be an effective treatment for patients affected by mental retardation in whom disruptive and drug-refractory aggressive behavior coexists. Although several experimental data are available on this target, further studies are necessary to confirm the long-term efficacy and safety of this procedure. Copyright © 2013. Published by Elsevier Inc.
Choi, Ja Young; Choi, Yoon Seong; Rha, Dong-Wook; Park, Eun Sook
2016-08-01
In the present study we investigated the nature and extent of clinical outcomes using various classifications and analyzed the relationship between brain magnetic resonance imaging (MRI) findings and the extent of clinical outcomes in children with cerebral palsy (CP) with deep gray matter injury. The deep gray matter injuries of 69 children were classified into hypoxic ischemic encephalopathy (HIE) and kernicterus patterns. HIE patterns were divided into four groups (I-IV) based on severity. Functional classification was investigated using the gross motor function classification system-expanded and revised, manual ability classification system, communication function classification system, and tests of cognitive function, and other associated problems. The severity of HIE pattern on brain MRI was strongly correlated with the severity of clinical outcomes in these various domains. Children with a kernicterus pattern showed a wide range of clinical outcomes in these areas. Children with severe HIE are at high risk of intellectual disability (ID) or epilepsy and children with a kernicterus pattern are at risk of hearing impairment and/or ID. Grading severity of HIE pattern on brain MRI is useful for predicting overall outcomes. The clinical outcomes of children with a kernicterus pattern range widely from mild to severe. Delineation of the clinical outcomes of children with deep gray matter injury, which are a common abnormal brain MRI finding in children with CP, is necessary. The present study provides clinical outcomes for various domains in children with deep gray matter injury on brain MRI. The deep gray matter injuries were divided into two major groups; HIE and kernicterus patterns. Our study showed that severity of HIE pattern on brain MRI was strongly associated with the severity of impairments in gross motor function, manual ability, communication function, and cognition. These findings suggest that severity of HIE pattern can be useful for predicting the
Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma
Kroeger, Daniel; Florea, Bogdan; Amzica, Florin
2013-01-01
The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669
Scharpf, Danielle Teresa; Sharma, Mayur; Deogaonkar, Milind; Rezai, Ali; Bergese, Sergio D
2015-08-01
The field of functional neurosurgery has expanded in last decade to include newer indications, new devices, and new methods. This advancement has challenged anesthesia providers to adapt to these new requirements. This review aims to discuss the nuances and practical issues that are faced while administering anesthesia for deep brain stimulation surgery.
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.
Deep brain stimulation of nucleus accumbens region in alcoholism affects reward processing.
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.
[Deep brain stimulation in parkinsonian patients with dopa intolerance].
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.
Novel targets and stimulation paradigms for deep brain stimulation.
De Jesus, Sol; Almeida, Leonardo; Peng-Chen, Zhongxing; Okun, Michael S; Hess, Christopher W
2015-01-01
Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.
Authenticity and autonomy in deep-brain stimulation.
Wardrope, Alistair
2014-08-01
Felicitas Kraemer draws on the experiences of patients undergoing deep-brain stimulation (DBS) to propose two distinct and potentially conflicting principles of respect: for an individual's autonomy (interpreted as mental competence), and for their authenticity. I argue instead that, according to commonly-invoked justifications of respect for autonomy, authenticity is itself in part constitutive of an analysis of autonomy worthy of respect; Kraemer's argument thus highlights the shortcomings of practical applications of respect for autonomy that emphasise competence while neglecting other important dimensions of autonomy such as authenticity, since it shows that competence alone cannot be interpreted as a reliable indicator of an individual's capacity for exercising autonomy. I draw from relational accounts to suggest how respect for a more expansive conception of autonomy might be interpreted for individuals undergoing DBS and in general. 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.
Landmark-based deep multi-instance learning for brain disease diagnosis.
Liu, Mingxia; Zhang, Jun; Adeli, Ehsan; Shen, Dinggang
2018-01-01
In conventional Magnetic Resonance (MR) image based methods, two stages are often involved to capture brain structural information for disease diagnosis, i.e., 1) manually partitioning each MR image into a number of regions-of-interest (ROIs), and 2) extracting pre-defined features from each ROI for diagnosis with a certain classifier. However, these pre-defined features often limit the performance of the diagnosis, due to challenges in 1) defining the ROIs and 2) extracting effective disease-related features. In this paper, we propose a landmark-based deep multi-instance learning (LDMIL) framework for brain disease diagnosis. Specifically, we first adopt a data-driven learning approach to discover disease-related anatomical landmarks in the brain MR images, along with their nearby image patches. Then, our LDMIL framework learns an end-to-end MR image classifier for capturing both the local structural information conveyed by image patches located by landmarks and the global structural information derived from all detected landmarks. We have evaluated our proposed framework on 1526 subjects from three public datasets (i.e., ADNI-1, ADNI-2, and MIRIAD), and the experimental results show that our framework can achieve superior performance over state-of-the-art approaches. Copyright © 2017 Elsevier B.V. All rights reserved.
Middlebrooks, E H; Tuna, I S; Grewal, S S; Almeida, L; Heckman, M G; Lesser, E R; Foote, K D; Okun, M S; Holanda, V M
2018-06-01
Although globus pallidus internus deep brain stimulation is a widely accepted treatment for Parkinson disease, there is persistent variability in outcomes that is not yet fully understood. In this pilot study, we aimed to investigate the potential role of globus pallidus internus segmentation using probabilistic tractography as a supplement to traditional targeting methods. Eleven patients undergoing globus pallidus internus deep brain stimulation were included in this retrospective analysis. Using multidirection diffusion-weighted MR imaging, we performed probabilistic tractography at all individual globus pallidus internus voxels. Each globus pallidus internus voxel was then assigned to the 1 ROI with the greatest number of propagated paths. On the basis of deep brain stimulation programming settings, the volume of tissue activated was generated for each patient using a finite element method solution. For each patient, the volume of tissue activated within each of the 10 segmented globus pallidus internus regions was calculated and examined for association with a change in the Unified Parkinson Disease Rating Scale, Part III score before and after treatment. Increasing volume of tissue activated was most strongly correlated with a change in the Unified Parkinson Disease Rating Scale, Part III score for the primary motor region (Spearman r = 0.74, P = .010), followed by the supplementary motor area/premotor cortex (Spearman r = 0.47, P = .15). In this pilot study, we assessed a novel method of segmentation of the globus pallidus internus based on probabilistic tractography as a supplement to traditional targeting methods. Our results suggest that our method may be an independent predictor of deep brain stimulation outcome, and evaluation of a larger cohort or prospective study is warranted to validate these findings. © 2018 by American Journal of Neuroradiology.
2013-01-01
Background Observation of the signals recorded from the extremities of Parkinson’s disease patients showing rest and/or action tremor reveal a distinct high power resonance peak in the frequency band corresponding to tremor. The aim of the study was to investigate, using quantitative measures, how clinically effective and less effective deep brain stimulation protocols redistribute movement power over the frequency bands associated with movement, pathological and physiological tremor, and whether normal physiological tremor may reappear during those periods that tremor is absent. Methods The power spectral density patterns of rest and action tremor were studied in 7 Parkinson’s disease patients treated with (bilateral) deep brain stimulation of the subthalamic nucleus. Two tests were carried out: 1) the patient was sitting at rest; 2) the patient performed a hand or foot tapping movement. Each test was repeated four times for each extremity with different stimulation settings applied during each repetition. Tremor intermittency was taken into account by classifying each 3-second window of the recorded angular velocity signals as a tremor or non-tremor window. Results The distribution of power over the low frequency band (<3.5 Hz – voluntary movement), tremor band (3.5-7.5 Hz) and high frequency band (>7.5 Hz – normal physiological tremor) revealed that rest and action tremor show a similar power-frequency shift related to tremor absence and presence: when tremor is present most power is contained in the tremor frequency band; when tremor is absent lower frequencies dominate. Even under resting conditions a relatively large low frequency component became prominent, which seemed to compensate for tremor. Tremor absence did not result in the reappearance of normal physiological tremor. Conclusion Parkinson’s disease patients continuously balance between tremor and tremor suppression or compensation expressed by power shifts between the low frequency band and
Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude
2017-01-01
Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100 ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250 ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. PMID:27039703
Deep 3D convolution neural network for CT brain hemorrhage classification
NASA Astrophysics Data System (ADS)
Jnawali, Kamal; Arbabshirani, Mohammad R.; Rao, Navalgund; Patel, Alpen A.
2018-02-01
Intracranial hemorrhage is a critical conditional with the high mortality rate that is typically diagnosed based on head computer tomography (CT) images. Deep learning algorithms, in particular, convolution neural networks (CNN), are becoming the methodology of choice in medical image analysis for a variety of applications such as computer-aided diagnosis, and segmentation. In this study, we propose a fully automated deep learning framework which learns to detect brain hemorrhage based on cross sectional CT images. The dataset for this work consists of 40,367 3D head CT studies (over 1.5 million 2D images) acquired retrospectively over a decade from multiple radiology facilities at Geisinger Health System. The proposed algorithm first extracts features using 3D CNN and then detects brain hemorrhage using the logistic function as the last layer of the network. Finally, we created an ensemble of three different 3D CNN architectures to improve the classification accuracy. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve of the ensemble of three architectures was 0.87. Their results are very promising considering the fact that the head CT studies were not controlled for slice thickness, scanner type, study protocol or any other settings. Moreover, the proposed algorithm reliably detected various types of hemorrhage within the skull. This work is one of the first applications of 3D CNN trained on a large dataset of cross sectional medical images for detection of a critical radiological condition
Faria, Miguel A.
2013-01-01
Knowledge of neuroscience flourished during and in the wake of the era of frontal lobotomy, as a byproduct of psychosurgery in the late 1930s and 1940s, revealing fascinating neural pathways and neurophysiologic mechanisms of the limbic system for the formulation of emotions, memory, and human behavior. The creation of the Klüver-Bucy syndrome in monkeys opened new horizons in the pursuit of knowledge in human behavior and neuropathology. In the 1950s specialized functional neurosurgery was developed in association with stereotactic neurosurgery; deep brain electrodes were implanted for more precise recording of brain electrical activity in the evaluation and treatment of intractable mental disorders, including schizophrenia, “pathologic aggression,” and psychomotor seizures in temporal lobe epilepsy. Psychosurgical procedures involved deep brain stimulation of the limbic system, as well as ablative procedures, such as cingulotomy and thalamotomy. The history of these developments up to the 21st century will continue in this three-part essay-editorial, exclusively researched and written for the readers of Surgical Neurology International. PMID:23776761
LeMoyne, Robert; Tomycz, Nestor; Mastroianni, Timothy; McCandless, Cyrus; Cozza, Michael; Peduto, David
2015-01-01
Essential tremor (ET) is a highly prevalent movement disorder. Patients with ET exhibit a complex progressive and disabling tremor, and medical management often fails. Deep brain stimulation (DBS) has been successfully applied to this disorder, however there has been no quantifiable way to measure tremor severity or treatment efficacy in this patient population. The quantified amelioration of kinetic tremor via DBS is herein demonstrated through the application of a smartphone (iPhone) as a wireless accelerometer platform. The recorded acceleration signal can be obtained at a setting of the subject's convenience and conveyed by wireless transmission through the Internet for post-processing anywhere in the world. Further post-processing of the acceleration signal can be classified through a machine learning application, such as the support vector machine. Preliminary application of deep brain stimulation with a smartphone for acquisition of a feature set and machine learning for classification has been successfully applied. The support vector machine achieved 100% classification between deep brain stimulation in `on' and `off' mode based on the recording of an accelerometer signal through a smartphone as a wireless accelerometer platform.
NASA Astrophysics Data System (ADS)
Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C. M.; Chen, Zhong
2017-08-01
Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy "functional" reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions
Carbon nanotube yarns for deep brain stimulation electrode.
Jiang, Changqing; Li, Luming; Hao, Hongwei
2011-12-01
A new form of deep brain stimulation (DBS) electrode was proposed that was made of carbon nanotube yarns (CNTYs). Electrode interface properties were examined using cyclic voltammetry (CV) and electrochemical impedance spectrum (EIS). The CNTY electrode interface exhibited large charge storage capacity (CSC) of 12.3 mC/cm(2) which increased to 98.6 mC/cm(2) after acid treatment, compared with 5.0 mC/cm(2) of Pt-Ir. Impedance spectrum of both untreated and treated CNTY electrodes showed that finite diffusion process occurred at the interface due to their porous structure and charge was delivered through capacitive mechanism. To evaluate stability electrical stimulus was exerted for up to 72 h and CV and EIS results of CNTY electrodes revealed little alteration. Therefore CNTY could make a good electrode material for DBS.
2017-01-01
Decoding neural activities related to voluntary and involuntary movements is fundamental to understanding human brain motor circuits and neuromotor disorders and can lead to the development of neuromotor prosthetic devices for neurorehabilitation. This study explores using recorded deep brain local field potentials (LFPs) for robust movement decoding of Parkinson's disease (PD) and Dystonia patients. The LFP data from voluntary movement activities such as left and right hand index finger clicking were recorded from patients who underwent surgeries for implantation of deep brain stimulation electrodes. Movement-related LFP signal features were extracted by computing instantaneous power related to motor response in different neural frequency bands. An innovative neural network ensemble classifier has been proposed and developed for accurate prediction of finger movement and its forthcoming laterality. The ensemble classifier contains three base neural network classifiers, namely, feedforward, radial basis, and probabilistic neural networks. The majority voting rule is used to fuse the decisions of the three base classifiers to generate the final decision of the ensemble classifier. The overall decoding performance reaches a level of agreement (kappa value) at about 0.729 ± 0.16 for decoding movement from the resting state and about 0.671 ± 0.14 for decoding left and right visually cued movements. PMID:29201041
Han, J W; Van Leeuwen, G M; Mizushina, S; Van de Kamer, J B; Maruyama, K; Sugiura, T; Azzopardi, D V; Edwards, A D
2001-07-01
In this study we present a design for a multi-frequency microwave radiometer aimed at prolonged monitoring of deep brain temperature in newborn infants and suitable for use during hypothermic neural rescue therapy. We identify appropriate hardware to measure brightness temperature and evaluate the accuracy of the measurements. We describe a method to estimate the tissue temperature distribution from measured brightness temperatures which uses the results of numerical simulations of the tissue temperature as well as the propagation of the microwaves in a realistic detailed three-dimensional infant head model. The temperature retrieval method is then used to evaluate how the statistical fluctuations in the measured brightness temperatures limit the confidence interval for the estimated temperature: for an 18 degrees C temperature differential between cooled surface and deep brain we found a standard error in the estimated central brain temperature of 0.75 degrees C. Evaluation of the systematic errors arising from inaccuracies in model parameters showed that realistic deviations in tissue parameters have little impact compared to uncertainty in the thickness of the bolus between the receiving antenna and the infant's head or in the skull thickness. This highlights the need to pay particular attention to these latter parameters in future practical implementation of the technique.
Frameless stereotaxy using bone fiducial markers for deep brain stimulation.
Holloway, Kathryn L; Gaede, Steven E; Starr, Philip A; Rosenow, Joshua M; Ramakrishnan, Viswanathan; Henderson, Jaimie M
2005-09-01
Functional neurosurgical interventions such as deep brain stimulation (DBS) are traditionally performed with the aid of a stereotactic frame. Although frameless techniques have been perceived as less accurate, data from a recent phantom study of a modified frameless approach demonstrated a laboratory accuracy exceeding that obtained using a common frame system. The present study was conducted to evaluate the accuracy of a frameless system in routine clinical use. Deep brain stimulation leads were implanted in 38 patients by using a skull-mounted trajectory guide and an image-guided workstation. Registration was accomplished with bone fiducial markers. Final lead positions were measured on postoperative computerized tomography scans and compared with the planned lead positions. The accuracy of the Leksell frame within the clinical situation has been reported on in a recent study; these raw data served as a comparison data set. The difference between expected and actual lead locations in the x plane was 1.4 mm in the frame-based procedure and 1.6 mm in the frameless procedure. Similarly, the difference in the y plane was 1.6 mm in the frame-based system and 1.3 mm in the frameless one. The error was greatest in the z plane, that is, 1.7 mm in the frame-based method and 2 mm in the frameless system. Multivariate analysis of variance demonstrated no statistically significant difference in the accuracy of the two methods. The accuracy of the frame-based and frameless systems was not statistically significantly different (p = 0.22). Note, however, that frameless techniques offer advantages in patient comfort, separation of imaging from surgery, and decreased operating time.
Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin
2015-04-01
In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.
[Deep brain stimulation in the treatment of movement disorders].
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.
Deep brain stimulation surgery for alcohol addiction.
Voges, Juergen; Müller, Ulf; Bogerts, Bernhard; Münte, Thomas; Heinze, Hans-Jochen
2013-01-01
The consequences of chronic alcohol dependence cause important health and economic burdens worldwide. Relapse rates after standard treatment (medication and psychotherapy) are high. There is evidence from in vivo investigations and from studies in patients that the brain's reward system is critically involved in the development and maintenance of addictive behavior, suggesting that modification of this system could significantly improve the prognosis of addictive patients. Motivated by an accidental observation, we used the nucleus accumbens (NAc), which has a central position in the dopaminergic reward system for deep brain stimulation (DBS) of alcohol addiction. We report our first experiences with NAc DBS for alcohol dependence and review the literature addressing the mechanisms leading to addiction. Five patients were treated off-label with bilateral NAc DBS for severe alcohol addiction (average follow-up 38 months). All patients experienced significant and ongoing improvement of craving. Two patients remained completely abstinent for more than 4 years. NAc stimulation was tolerated without permanent side effects. Simultaneous recording of local field potentials from the target area and surface electroencephalography while patients performed neuropsychological tasks gave a hint on the pivotal role of the NAc in processing alcohol-related cues. To our knowledge, the data presented here reflect the first attempt to treat alcohol-addicted patients with NAc DBS. Electrical NAc stimulation probably counterbalances the effect of drug-related stimuli triggering involuntarily drug-seeking behavior. Meanwhile, two prospective clinical studies using randomized, double-blind, and crossover stimulation protocols for DBS are underway to corroborate these preliminary results. Published by Elsevier Inc.
Brain tumor segmentation with Deep Neural Networks.
Havaei, Mohammad; Davy, Axel; Warde-Farley, David; Biard, Antoine; Courville, Aaron; Bengio, Yoshua; Pal, Chris; Jodoin, Pierre-Marc; Larochelle, Hugo
2017-01-01
In this paper, we present a fully automatic brain tumor segmentation method based on Deep Neural Networks (DNNs). The proposed networks are tailored to glioblastomas (both low and high grade) pictured in MR images. By their very nature, these tumors can appear anywhere in the brain and have almost any kind of shape, size, and contrast. These reasons motivate our exploration of a machine learning solution that exploits a flexible, high capacity DNN while being extremely efficient. Here, we give a description of different model choices that we've found to be necessary for obtaining competitive performance. We explore in particular different architectures based on Convolutional Neural Networks (CNN), i.e. DNNs specifically adapted to image data. We present a novel CNN architecture which differs from those traditionally used in computer vision. Our CNN exploits both local features as well as more global contextual features simultaneously. Also, different from most traditional uses of CNNs, our networks use a final layer that is a convolutional implementation of a fully connected layer which allows a 40 fold speed up. We also describe a 2-phase training procedure that allows us to tackle difficulties related to the imbalance of tumor labels. Finally, we explore a cascade architecture in which the output of a basic CNN is treated as an additional source of information for a subsequent CNN. Results reported on the 2013 BRATS test data-set reveal that our architecture improves over the currently published state-of-the-art while being over 30 times faster. Copyright © 2016 Elsevier B.V. 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.
Deep brain stimulation in addiction due to psychoactive substance use.
Kuhn, Jens; Bührle, Christian P; Lenartz, Doris; Sturm, Volker
2013-01-01
Addiction is one of the most challenging health problems. It is associated with enormous individual distress and tremendous socioeconomic consequences. Unfortunately, its underlying mechanisms are not fully understood, and pharmacological, psychological, or social interventions often fail to achieve long-lasting remission. Next to genetic, social, and contextual factors, a substance-induced dysfunction of the brain's reward system is considered a decisive factor for the establishment and maintenance of addiction. Due to its successful application and approval for several neurological disorders, deep brain stimulation (DBS) is known as a powerful tool for modulating dysregulated networks and has also been considered for substance addiction. Initial promising case reports of DBS in alcohol and heroin addiction in humans have recently been published. Likewise, results from animal studies mimicking different kinds of substance addiction point in a similar direction. The objective of this review is to provide an overview of the published results on DBS in addiction, and to discuss whether these preliminary results justify further research, given the novelty of this treatment approach. © 2013 Elsevier B.V. All rights reserved.
Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.
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.
Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease
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
Deep brain stimulation for trigeminal autonomic cephalalgias.
Messina, Giuseppe; Broggi, Giovanni; Levi, Vincenzo; Franzini, Angelo
2018-04-19
Deep brain stimulation (DBS) of the posterior hypothalamic region (pHyr) has been shown to be efficacious for more than a half of patients suffering from trigeminal autonomic cephalalgias (TACs); nonetheless, controversies about the mechanisms of action and the actual site of stimulation have arisen in recent years. Areas covered: Firstly, a review of the most recent literature on the subject is presented, stressing the critical points that could, in the future, make a difference for optimal management of patients afflicted by these life-threating diseases. Hypothalamic functional anatomy, experimental data and pathophysiological hypotheses are reported. Expert commentary: About 32% of patients who underwent DBS for TACs are pain-free. The determination of the pHyr region seems to be crucial for the generation of pain attack in these pathologies, although other structures are involved in complex mechanisms and circuits that interact with each other. Neurophysiological data, combined with more advanced experimental models, are of primary importance regarding our understanding of what the real target is, and how to overcome the issue of refractory patients.
Characterizing Deep Brain Stimulation effects in computationally efficient neural network models.
Latteri, Alberta; Arena, Paolo; Mazzone, Paolo
2011-04-15
Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized. To study in details the effect of the stimulation signal on a pathological neural medium, efficient models of these neural structures were built, which are able to show, without any external input, the intrinsic properties of a pathological neural tissue, mimicking the BG synchronized dynamics.We start considering a model already introduced in the literature to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. This model used Morris Lecar type neurons. This neuron model, although having a high level of biological plausibility, requires a large computational effort
Martin Cichy, Radoslaw; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude
2017-06-01
Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Recurrent, Delayed Hemorrhage Associated with Edoxaban after Deep Brain Stimulation Lead Placement
Garber, Sarah T.; Schrock, Lauren E.; House, Paul A.
2013-01-01
Factor-Xa inhibitors like edoxaban have been shown to have comparable or superior rates of stroke and systemic embolization prevention to warfarin while exhibiting lower clinically significant bleeding rates. The authors report a case of a man who presented with delayed, recurrent intracranial hemorrhage months after successful deep brain stimulator placement for Parkinson disease while on edoxaban for atrial fibrillation. Further reports on the use of novel anticoagulants after intracranial surgery are acutely needed to help assess the true relative risk they pose. PMID:23365773
Fang, Jinsheng; Bao, Lijun; Li, Xu; van Zijl, Peter C M; Chen, Zhong
2017-08-01
Background field removal is an important MR phase preprocessing step for quantitative susceptibility mapping (QSM). It separates the local field induced by tissue magnetic susceptibility sources from the background field generated by sources outside a region of interest, e.g. brain, such as air-tissue interface. In the vicinity of air-tissue boundary, e.g. skull and paranasal sinuses, where large susceptibility variations exist, present background field removal methods are usually insufficient and these regions often need to be excluded by brain mask erosion at the expense of losing information of local field and thus susceptibility measures in these regions. In this paper, we propose an extension to the variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP) background field removal method using a region adaptive kernel (R-SHARP), in which a scalable spherical Gaussian kernel (SGK) is employed with its kernel radius and weights adjustable according to an energy "functional" reflecting the magnitude of field variation. Such an energy functional is defined in terms of a contour and two fitting functions incorporating regularization terms, from which a curve evolution model in level set formation is derived for energy minimization. We utilize it to detect regions of with a large field gradient caused by strong susceptibility variation. In such regions, the SGK will have a small radius and high weight at the sphere center in a manner adaptive to the voxel energy of the field perturbation. Using the proposed method, the background field generated from external sources can be effectively removed to get a more accurate estimation of the local field and thus of the QSM dipole inversion to map local tissue susceptibility sources. Numerical simulation, phantom and in vivo human brain data demonstrate improved performance of R-SHARP compared to V-SHARP and RESHARP (regularization enabled SHARP) methods, even when the whole paranasal sinus regions
NASA Astrophysics Data System (ADS)
Choi, Woo June; Wang, Ruikang K.
2015-10-01
We report noninvasive, in vivo optical imaging deep within a mouse brain by swept-source optical coherence tomography (SS-OCT), enabled by a 1.3-μm vertical cavity surface emitting laser (VCSEL). VCSEL SS-OCT offers a constant signal sensitivity of 105 dB throughout an entire depth of 4.25 mm in air, ensuring an extended usable imaging depth range of more than 2 mm in turbid biological tissue. Using this approach, we show deep brain imaging in mice with an open-skull cranial window preparation, revealing intact mouse brain anatomy from the superficial cerebral cortex to the deep hippocampus. VCSEL SS-OCT would be applicable to small animal studies for the investigation of deep tissue compartments in living brains where diseases such as dementia and tumor can take their toll.
Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.
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.
ERIC Educational Resources Information Center
Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.
2008-01-01
Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…
Programming Deep Brain Stimulation for Parkinson's Disease: The Toronto Western Hospital Algorithms.
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.
Classification of brain MRI with big data and deep 3D convolutional neural networks
NASA Astrophysics Data System (ADS)
Wegmayr, Viktor; Aitharaju, Sai; Buhmann, Joachim
2018-02-01
Our ever-aging society faces the growing problem of neurodegenerative diseases, in particular dementia. Magnetic Resonance Imaging provides a unique tool for non-invasive investigation of these brain diseases. However, it is extremely difficult for neurologists to identify complex disease patterns from large amounts of three-dimensional images. In contrast, machine learning excels at automatic pattern recognition from large amounts of data. In particular, deep learning has achieved impressive results in image classification. Unfortunately, its application to medical image classification remains difficult. We consider two reasons for this difficulty: First, volumetric medical image data is considerably scarcer than natural images. Second, the complexity of 3D medical images is much higher compared to common 2D images. To address the problem of small data set size, we assemble the largest dataset ever used for training a deep 3D convolutional neural network to classify brain images as healthy (HC), mild cognitive impairment (MCI) or Alzheimers disease (AD). We use more than 20.000 images from subjects of these three classes, which is almost 9x the size of the previously largest data set. The problem of high dimensionality is addressed by using a deep 3D convolutional neural network, which is state-of-the-art in large-scale image classification. We exploit its ability to process the images directly, only with standard preprocessing, but without the need for elaborate feature engineering. Compared to other work, our workflow is considerably simpler, which increases clinical applicability. Accuracy is measured on the ADNI+AIBL data sets, and the independent CADDementia benchmark.
Urbanowicz, Tomasz K; Budniak, Wiktor; Buczkowski, Piotr; Perek, Bartłomiej; Walczak, Maciej; Tomczyk, Jadwiga; Katarzyński, Sławomir; Jemielity, Marek
2014-12-01
Monitoring the central nervous system during aortic dissection repair may improve the understanding of the intraoperative changes related to its bioactivity. The aim of the study was to evaluate the influence of deep hypothermia on intraoperative brain bioactivity measured by the compressed spectral array (CSA) method and to assess the influence of the operations on postoperative cognitive function. The study enrolled 40 patients (31 men and 9 women) at the mean age of 60.2 ± 8.6 years, diagnosed with acute aortic dissection. They underwent emergency operations in deep hypothermic circulatory arrest (DHCA). During the operations, brain bioactivity was monitored with the compressed spectral array method. There were no intraoperative deaths. Electrocerebral silence during DHCA was observed in 31 patients (74%). The lowest activity was observed during DHCA: it was 0.01 ± 0.05 nW in the left hemisphere and 0.01 ± 0.03 nW in the right hemisphere. The postoperative results of neurological tests deteriorated statistically significantly (26.9 ± 1.7 points vs. 22.0 ± 1.7 points; p < 0.001), especially among patients who exhibited brain activity during DHCA. The compressed spectral array method is clinically useful in monitoring brain bioactivity during emergency operations of acute aortic dissections. Electrocerebral silence occurs in 75% of patients during DHCA. The cognitive function of patients deteriorates significantly after operations with DHCA.
Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lau, Steven; Lu, Weiguo; Yan, Yulong; Jiang, Steve B.; Zhen, Xin; Timmerman, Robert; Nedzi, Lucien
2017-01-01
Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases. PMID:28985229
Liu, Yan; Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lau, Steven; Lu, Weiguo; Yan, Yulong; Jiang, Steve B; Zhen, Xin; Timmerman, Robert; Nedzi, Lucien; Gu, Xuejun
2017-01-01
Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.
Hou, Jin; Wang, Wei; Quan, Xianyue; Liang, Wen; Li, Zhiming; Chen, Deji; Han, Hongbin
2017-09-03
BACKGROUND This study assessed an innovative tracer-based magnetic resonance imaging (MRI) system to visualize the dynamic transportation of tracers in regions of deep brain extracellular space (ECS) and to measure transportation ability and ECS structure. MATERIAL AND METHODS Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) was the chosen tracer and was injected into the caudate nucleus and thalamus. Real-time dynamic transportation of Gd-DTPA in ECS was observed and the results were verified by laser scanning confocal microscopy. Using Transwell assay across the blood-brain barrier, a modified diffusion equation was further simplified. Effective diffusion coefficient D* and tortuosity λ were calculated. Immunohistochemical staining and Western blot analysis were used to investigate the extracellular matrix contributing to ECS structure. RESULTS Tracers injected into the caudate nucleus were transported to the ipsilateral frontal and temporal cortices away from the injection points, while both of them injected into the thalamus were only distributed on site. Although the caudate nucleus was closely adjacent to the thalamus, tracer transportation between partitions was not observed. In addition, D* and the λ showed statistically significant differences between partitions. ECS was shown to be a physiologically partitioned system, and its division is characterized by the unique distribution territory and transportation ability of substances located in it. Versican and Tenascin R are possible contributors to the tortuosity of ECS. CONCLUSIONS Tracer-based MRI will improve our understanding of the brain microenvironment, improve the techniques for local delivery of drugs, and highlight brain tissue engineering fields in the future.
The Role of a Neuropsychologist on a Movement Disorders Deep Brain Stimulation Team.
Kubu, Cynthia S
2018-05-01
The term movement disorders is misleading in the implication that the symptoms are limited to motor problems. Most movement disorders include a variety of neurobehavioral and neurocognitive symptoms that require neuropsychological expertise. The goal of this paper is to provide a rationale and practical roadmap for neuropsychologists' involvement in a Movement Disorders team with a specific focus on pre-operative deep brain stimulation (DBS) evaluations. Pragmatic recommendations regarding requisite skills, clinical practice, recommendations, communication, and benefits are outlined.
Assessing the direct effects of deep brain stimulation using embedded axon models
NASA Astrophysics Data System (ADS)
Sotiropoulos, Stamatios N.; Steinmetz, Peter N.
2007-06-01
To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.
Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation
2015-10-01
currently investigating the effects of CG stimulation in subjects with debilitating pain due to cervical or thoracic SCI. This study stemmed from...had a low thoracic injury and pain in lumbar dermatomes, whereas Subject 1 had mainly mid- cervical pain that responded minimally to DBS and matched...AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation PRINCIPAL
Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A
2014-01-01
Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico
Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease
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
Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts
Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.
2016-01-01
Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680
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
Closing the loop of deep brain stimulation
Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance
2013-01-01
High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555
Closing the loop of deep brain stimulation.
Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance
2013-12-20
High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.
Minimally invasive multimode optical fiber microendoscope for deep brain fluorescence imaging
Ohayon, Shay; Caravaca-Aguirre, Antonio; Piestun, Rafael; DiCarlo, James J.
2018-01-01
A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive multi-photon approaches for deep (>2mm) structures, while gradient refractive index (GRIN) endoscopes are relatively thick and can cause significant damage upon insertion. Here, we present a novel micro-endoscope design to image neural activity at arbitrary depths via an ultra-thin multi-mode optical fiber (MMF) probe that has 5–10X thinner diameter than commercially available micro-endoscopes. We demonstrate micron-scale resolution, multi-spectral and volumetric imaging. In contrast to previous approaches, we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator (GCaMP). Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions. PMID:29675297
Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease.
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.
Student beats the teacher: deep neural networks for lateral ventricles segmentation in brain MR
NASA Astrophysics Data System (ADS)
Ghafoorian, Mohsen; Teuwen, Jonas; Manniesing, Rashindra; Leeuw, Frank-Erik d.; van Ginneken, Bram; Karssemeijer, Nico; Platel, Bram
2018-03-01
Ventricular volume and its progression are known to be linked to several brain diseases such as dementia and schizophrenia. Therefore accurate measurement of ventricle volume is vital for longitudinal studies on these disorders, making automated ventricle segmentation algorithms desirable. In the past few years, deep neural networks have shown to outperform the classical models in many imaging domains. However, the success of deep networks is dependent on manually labeled data sets, which are expensive to acquire especially for higher dimensional data in the medical domain. In this work, we show that deep neural networks can be trained on muchcheaper-to-acquire pseudo-labels (e.g., generated by other automated less accurate methods) and still produce more accurate segmentations compared to the quality of the labels. To show this, we use noisy segmentation labels generated by a conventional region growing algorithm to train a deep network for lateral ventricle segmentation. Then on a large manually annotated test set, we show that the network significantly outperforms the conventional region growing algorithm which was used to produce the training labels for the network. Our experiments report a Dice Similarity Coefficient (DSC) of 0.874 for the trained network compared to 0.754 for the conventional region growing algorithm (p < 0.001).
Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression
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. PMID:29618967
Deep brain stimulation of anterior nucleus thalami disrupts sleep in epilepsy patients.
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.
Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang
2016-01-01
Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543
Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang
2016-01-01
Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.
Face-Name Association Learning and Brain Structural Substrates in Alcoholism
Pitel, Anne-Lise; Chanraud, Sandra; Rohlfing, Torsten; Pfefferbaum, Adolf; Sullivan, Edith V.
2011-01-01
Background Associative learning is required for face-name association and is impaired in alcoholism, but the cognitive processes and brain structural components underlying this deficit remain unclear. It is also unknown whether prompting alcoholics to implement a deep level of processing during face-name encoding would enhance performance. Methods Abstinent alcoholics and controls performed a levels-of-processing face-name learning task. Participants indicated whether the face was that of an honest person (deep encoding) or that of a man (shallow encoding). Retrieval was examined using an associative (face-name) recognition task and a single-item (face or name only) recognition task. Participants also underwent a 3T structural MRI. Results Compared with controls, alcoholics had poorer associative and single-item recognition, each impaired to the same extent. Level of processing at encoding had little effect on recognition performance but affected reaction time. Correlations with brain volumes were generally modest and based primarily on reaction time in alcoholics, where the deeper the processing at encoding, the more restricted the correlations with brain volumes. In alcoholics, longer control task reaction times correlated modestly with volumes across several anterior to posterior brain regions; shallow encoding correlated with calcarine and striatal volumes; deep encoding correlated with precuneus and parietal volumes; associative recognition RT correlated with cerebellar volumes. In controls, poorer associative recognition with deep encoding correlated significantly with smaller volumes of frontal and striatal structures. Conclusions Despite prompting, alcoholics did not take advantage of encoding memoranda at a deep level to enhance face-name recognition accuracy. Nonetheless, conditions of deeper encoding resulted in faster reaction times and more specific relations with regional brain volumes than did shallow encoding. The normal relation between associative
Martinez-Ramirez, Daniel; Rossi, Peter J.; Peng, Zhongxing; Gunduz, Aysegul; Okun, Michael S.
2015-01-01
Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome. PMID:25851890
DeepNeuron: an open deep learning toolbox for neuron tracing.
Zhou, Zhi; Kuo, Hsien-Chi; Peng, Hanchuan; Long, Fuhui
2018-06-06
Reconstructing three-dimensional (3D) morphology of neurons is essential for understanding brain structures and functions. Over the past decades, a number of neuron tracing tools including manual, semiautomatic, and fully automatic approaches have been developed to extract and analyze 3D neuronal structures. Nevertheless, most of them were developed based on coding certain rules to extract and connect structural components of a neuron, showing limited performance on complicated neuron morphology. Recently, deep learning outperforms many other machine learning methods in a wide range of image analysis and computer vision tasks. Here we developed a new Open Source toolbox, DeepNeuron, which uses deep learning networks to learn features and rules from data and trace neuron morphology in light microscopy images. DeepNeuron provides a family of modules to solve basic yet challenging problems in neuron tracing. These problems include but not limited to: (1) detecting neuron signal under different image conditions, (2) connecting neuronal signals into tree(s), (3) pruning and refining tree morphology, (4) quantifying the quality of morphology, and (5) classifying dendrites and axons in real time. We have tested DeepNeuron using light microscopy images including bright-field and confocal images of human and mouse brain, on which DeepNeuron demonstrates robustness and accuracy in neuron tracing.
NASA Astrophysics Data System (ADS)
Fins, Joseph J.; MD; FACP
2009-10-01
At the height of the psychosurgery debate the editors of The Lancet referenced the popular hesitancy to intervene surgically with the workings of the brain. They wrote that to do so `carries a peculiar penumbra of sacrilege' [1, 2]. Penumbra of sacrilege is a memorable, even strange phrase. It is one worth unpacking as we embark on an era which will see ever more border crossings at the blood-brain barrier. By invoking popular beliefs about a penumbra of sacrilege, the editors were suggesting that psychosurgery represented a gray zone in the shadows, a desecration or violation of a sacred space, the seat of the soul, the self. And as such, they were reflecting a cultural hesitancy, a lay reluctance to pursue this work. Fortunately for those with intractable neuropsychiatric disorders, neuromodulation has evolved beyond the primitive—and barbaric—sweep of the lobotomy, and with this advance, categorical resistance to this work has dissipated. And that is all to the good. But as the field progresses, and we implant more and more devices for therapeutic and investigational purposes, we must not let the placement of electrodes become too easy. It is a decision that should be made with full awareness of its implications for patients and families. Recently, I spoke to a friend who appeared to have early essential tremor. (Some non-essential aspects of this story have been changed to protect confidentiality.) He asked me, `Do you know anything about deep brain stimulation?' I indicated that I did. `Really?', he asked, seemingly unaware of my scholarly interest in the topic [3, 4, 5, 6] and involvement as a co-investigator in the use of deep brain stimulation in the minimally conscious state [7, 8, 9]. Satisfied that I might be a credible source for some free advice, he told me that his neurologist had sent him to a neurosurgeon to see about a stimulator. I asked him how disabling his condition was. As he competently drank a cup of soda, he told me it was a bit of a
General anaesthesia for deep brain stimulator electrode insertion in Parkinson's disease.
Sutcliffe, A J; Mitchell, R D; Gan, Y C; Mocroft, A P; Nightingale, P
2011-03-01
This paper compares the use of general and local anaesthetic in patients having deep brain stimulator (DBS) surgery. It is a retrospective case note study of 46 patients treated consecutively with subthalamic nucleus stimulation for Parkinson's disease as practise changed in a Neurosurgical unit. The first 20 patients (LA group) had permanent electrodes placed under local anaesthesia. The remaining 26 patients (GA group) had the entire procedure under general anaesthesia. The groups were similar for age, sex, duration of Parkinson's disease and preoperative levodopa requirement. The clinical results were similar in that within each group, the reduction in levodopa was not only clinically but also statistically significant (p < 0.001 for both, paired t test): for the LA group, the 6-month requirement was 39.4% (29.5-52.6%) of the preoperative requirement and for the GA group, the 6-month requirement was 32.3% (25.2-41.5%) of the preoperative requirement. The reduction in levodopa was maintained at 1 year. Of note, duration of surgery and length of stay were reduced. The mean duration of surgery was 8.2 h (7.8-8.6) for the LA group and 7.5 h (7.2-7.8) for the GA group (p = 0.003). The geometric mean of length of hospital stay was 5.4 days(4.6-6.3) for the LA group and 3.8 days (3.4-4.4) for the GA group (p = 0.001) There was no difference in electrophysiological recording. This study describes benefits in the GA group for the entire procedure of STN DBS. In these samples, there was no difference in the adverse effects seen in patients undergoing deep brain stimulator insertion with general anaesthetic compared with local anaesthetic. The use of general anaesthetic did not detract from the known benefits of surgery.
ERIC Educational Resources Information Center
Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine
2011-01-01
Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…
Informed Consent Decision-Making in Deep Brain Stimulation.
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.
A foldable electrode array for 3D recording of deep-seated abnormal brain cavities
NASA Astrophysics Data System (ADS)
Kil, Dries; De Vloo, Philippe; Fierens, Guy; Ceyssens, Frederik; Hunyadi, Borbála; Bertrand, Alexander; Nuttin, Bart; Puers, Robert
2018-06-01
Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.
Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling
NASA Astrophysics Data System (ADS)
Béduer, Amélie; Joris, Pierre; Mosser, Sébastien; Fraering, Patrick C.; Renaud, Philippe
2015-04-01
Objective. Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (Aß) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study, we investigated if we could monitor the presence of these aggregates by performing in situ electrical impedance spectroscopy measurements in AD model mice brains. Approach. In this study, electrical impedance spectroscopy measurements were performed post-mortem in APPPS1 transgenic mice brains. This transgenic model is commonly used to study amyloidogenesis, a pathological hallmark of AD. We used flexible probes with embedded micrometric electrodes array to demonstrate the feasibility of detecting senile plaques composed of Aß peptides by localized impedance measurements. Main results. We particularly focused on deep brain structures, such as the hippocampus. Ex vivo experiments using brains from young and old APPPS1 mice lead us to show that impedance measurements clearly correlate with the percentage of Aβ plaque load in the brain tissues. We could monitor the effects of aging in the AD APPPS1 mice model. Significance. We demonstrated that a localized electrical impedance measurement constitutes a valuable technique to monitor the presence of Aβ-plaques, which is complementary with existing imaging techniques. This method does not require prior Aβ staining, precluding the risk of variations in tissue uptake of dyes or tracers, and consequently ensuring reproducible data collection.
Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy.
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.
Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy
Barretto, Robert P. J.; Ko, Tony H.; Jung, Juergen C.; Wang, Tammy J.; Capps, George; Waters, Allison C.; Ziv, Yaniv; Attardo, Alessio; Recht, Lawrence; Schnitzer, Mark J.
2013-01-01
The combination of intravital microscopy and animal models of disease has propelled studies of disease mechanisms and treatments. However, many disorders afflict tissues inaccessible to light microscopy in live subjects. Here we introduce cellular-level time-lapse imaging deep within the live mammalian brain by one- and two-photon fluorescence microendoscopy over multiple weeks. Bilateral imaging sites allowed longitudinal comparisons within individual subjects, including of normal and diseased tissues. Using this approach we tracked CA1 hippocampal pyramidal neuron dendrites in adult mice, revealing these dendrites' extreme stability (>8,000 day mean lifetime) and rare examples of their structural alterations. To illustrate disease studies, we tracked deep lying gliomas by observing tumor growth, visualizing three-dimensional vasculature structure, and determining microcirculatory speeds. Average erythrocyte speeds in gliomas declined markedly as the disease advanced, notwithstanding significant increases in capillary diameters. Time-lapse microendoscopy will be applicable to studies of numerous disorders, including neurovascular, neurological, cancerous, and trauma-induced conditions. PMID:21240263
Hemodynamic measurements in deep brain tissues of humans by near-infrared time-resolved spectroscopy
NASA Astrophysics Data System (ADS)
Suzuki, Hiroaki; Oda, Motoki; Yamaki, Etsuko; Suzuki, Toshihiko; Yamashita, Daisuke; Yoshimoto, Kenji; Homma, Shu; Yamashita, Yutaka
2014-03-01
Using near-infrared time-resolved spectroscopy (TRS), we measured the human head in transmittance mode to obtain the optical properties, tissue oxygenation, and hemodynamics of deep brain tissues in 50 healthy adult volunteers. The right ear canal was irradiated with 3-wavelengths of pulsed light (760, 795, and 835nm), and the photons passing through the human head were collected at the left ear canal. Optical signals with sufficient intensity could be obtained from 46 of the 50 volunteers. By analyzing the temporal profiles based on the photon diffusion theory, we successfully obtained absorption coefficients for each wavelength. The levels of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), total hemoglobin (tHb), and tissue oxygen saturation (SO2) were then determined by referring to the hemoglobin spectroscopic data. Compared with the SO2 values for the forehead measurements in reflectance mode, the SO2 values of the transmittance measurements of the human head were approximately 10% lower, and tHb values of the transmittance measurements were always lower than those of the forehead reflectance measurements. Moreover, the level of hemoglobin and the SO2 were strongly correlated between the human head measurements in transmittance mode and the forehead measurements in the reflectance mode, respectively. These results demonstrated a potential application of this TRS system in examining deep brain tissues of humans.
Pinaya, Walter H. L.; Gadelha, Ary; Doyle, Orla M.; Noto, Cristiano; Zugman, André; Cordeiro, Quirino; Jackowski, Andrea P.; Bressan, Rodrigo A.; Sato, João R.
2016-01-01
Neuroimaging-based models contribute to increasing our understanding of schizophrenia pathophysiology and can reveal the underlying characteristics of this and other clinical conditions. However, the considerable variability in reported neuroimaging results mirrors the heterogeneity of the disorder. Machine learning methods capable of representing invariant features could circumvent this problem. In this structural MRI study, we trained a deep learning model known as deep belief network (DBN) to extract features from brain morphometry data and investigated its performance in discriminating between healthy controls (N = 83) and patients with schizophrenia (N = 143). We further analysed performance in classifying patients with a first-episode psychosis (N = 32). The DBN highlighted differences between classes, especially in the frontal, temporal, parietal, and insular cortices, and in some subcortical regions, including the corpus callosum, putamen, and cerebellum. The DBN was slightly more accurate as a classifier (accuracy = 73.6%) than the support vector machine (accuracy = 68.1%). Finally, the error rate of the DBN in classifying first-episode patients was 56.3%, indicating that the representations learned from patients with schizophrenia and healthy controls were not suitable to define these patients. Our data suggest that deep learning could improve our understanding of psychiatric disorders such as schizophrenia by improving neuromorphometric analyses. PMID:27941946
NASA Astrophysics Data System (ADS)
Pinaya, Walter H. L.; Gadelha, Ary; Doyle, Orla M.; Noto, Cristiano; Zugman, André; Cordeiro, Quirino; Jackowski, Andrea P.; Bressan, Rodrigo A.; Sato, João R.
2016-12-01
Neuroimaging-based models contribute to increasing our understanding of schizophrenia pathophysiology and can reveal the underlying characteristics of this and other clinical conditions. However, the considerable variability in reported neuroimaging results mirrors the heterogeneity of the disorder. Machine learning methods capable of representing invariant features could circumvent this problem. In this structural MRI study, we trained a deep learning model known as deep belief network (DBN) to extract features from brain morphometry data and investigated its performance in discriminating between healthy controls (N = 83) and patients with schizophrenia (N = 143). We further analysed performance in classifying patients with a first-episode psychosis (N = 32). The DBN highlighted differences between classes, especially in the frontal, temporal, parietal, and insular cortices, and in some subcortical regions, including the corpus callosum, putamen, and cerebellum. The DBN was slightly more accurate as a classifier (accuracy = 73.6%) than the support vector machine (accuracy = 68.1%). Finally, the error rate of the DBN in classifying first-episode patients was 56.3%, indicating that the representations learned from patients with schizophrenia and healthy controls were not suitable to define these patients. Our data suggest that deep learning could improve our understanding of psychiatric disorders such as schizophrenia by improving neuromorphometric analyses.
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.
Technological Advances in Deep Brain Stimulation.
Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars
2015-01-01
Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware.
Deep brain stimulation for Parkinson's disease: recent trends and future direction.
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.
Kinfe, Thomas M; Vesper, Jan
2013-01-01
Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.
Differential effects of deep brain stimulation on verbal fluency.
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.
Katnani, Husam A; Patel, Shaun R; Kwon, Churl-Su; Abdel-Aziz, Samer; Gale, John T; Eskandar, Emad N
2016-01-04
The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect.
High-speed swept source optical coherence Doppler tomography for deep brain microvascular imaging
NASA Astrophysics Data System (ADS)
Chen, Wei; You, Jiang; Gu, Xiaochun; Du, Congwu; Pan, Yingtian
2016-12-01
Noninvasive microvascular imaging using optical coherence Doppler tomography (ODT) has shown great promise in brain studies; however, high-speed microcirculatory imaging in deep brain remains an open quest. A high-speed 1.3 μm swept-source ODT (SS-ODT) system is reported which was based on a 200 kHz vertical-cavity-surface-emitting laser. Phase errors induced by sweep-trigger desynchronization were effectively reduced by spectral phase encoding and instantaneous correlation among the A-scans. Phantom studies have revealed a significant reduction in phase noise, thus an enhancement of minimally detectable flow down to 268.2 μm/s. Further in vivo validation was performed, in which 3D cerebral-blood-flow (CBF) networks in mouse brain over a large field-of-view (FOV: 8.5 × 5 × 3.2 mm3) was scanned through thinned skull. Results showed that fast flows up to 3 cm/s in pial vessels and minute flows down to 0.3 mm/s in arterioles or venules were readily detectable at depths down to 3.2 mm. Moreover, the dynamic changes of the CBF networks elicited by acute cocaine such as heterogeneous responses in various vessel compartments and at different cortical layers as well as transient ischemic events were tracked, suggesting the potential of SS-ODT for brain functional imaging that requires high flow sensitivity and dynamic range, fast frame rate and a large FOV to cover different brain regions.
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
Lightning may pose a danger to patients receiving deep brain stimulation: case report.
Prezelj, Neža; Trošt, Maja; Georgiev, Dejan; Flisar, Dušan
2018-05-01
Deep brain stimulation (DBS) is an established treatment option for advanced stages of Parkinson's disease and other movement disorders. It is known that DBS is susceptible to strong electromagnetic fields (EMFs) that can be generated by various electrical devices at work, home, and in medical environments. EMFs can interfere with the proper functioning of implantable pulse generators (IPGs). Very strong EMFs can generate induction currents in implanted electrodes and even damage the brain. Manufacturers of DBS devices have issued a list of warnings on how to avoid this danger. Strong EMFs can result from natural forces as well. The authors present the case of a 66-year-old woman who was being treated with a rechargeable DBS system for neck dystonia when her apartment was struck by lightning. Domestic electronic devices that were operating during the event were burned and destroyed. The woman's IPG switched off but remained undamaged, and she suffered no neurological consequences.
Deep brain stimulation for severe autism: from pathophysiology to procedure.
Sinha, Saurabh; McGovern, Robert A; Sheth, Sameer A
2015-06-01
Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.
Manjila, Sunil; Karhade, Aditya; Phi, Ji Hoon; Scott, R Michael; Smith, Edward R
2017-01-01
Brain shift during the exposure of cranial lesions may reduce the accuracy of frameless stereotaxy. We describe a rapid, safe, and effective method to approach deep-seated brain lesions using real-time intraoperative ultrasound placement of a catheter to mark the dissection trajectory to the lesion. With Institutional Review Board approval, we retrospectively reviewed the radiographic, pathologic, and intraoperative data of 11 pediatric patients who underwent excision of 12 lesions by means of this technique. Full data sets were available for 12 lesions in 11 patients. Ten lesions were tumors and 2 were cavernous malformations. Lesion locations included the thalamus (n = 4), trigone (n = 3), mesial temporal lobe (n = 3), and deep white matter (n = 2). Catheter placement was successful in all patients, and the median time required for the procedure was 3 min (range 2-5 min). There were no complications related to catheter placement. The median diameter of surgical corridors on postresection magnetic resonance imaging was 6.6 mm (range 3.0-12.1 mm). Use of real-time ultrasound guidance to place a catheter to aid in the dissection to reach a deep-seated brain lesion provides advantages complementary to existing techniques, such as frameless stereotaxy. The catheter insertion technique described here provides a quick, accurate, and safe method for reaching deep-seated lesions. © 2017 S. Karger AG, Basel.
Panic and fear induced by deep brain stimulation.
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.
Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome.
Ackermans, Linda; Duits, Annelien; Temel, Yasin; Winogrodzka, Ania; Peeters, Frenk; Beuls, Emile A M; Visser-Vandewalle, Veerle
2010-10-01
Thalamic deep brain stimulation for intractable Tourette Syndrome was introduced in 1999 by Vandewalle et al. In this follow-up study, the authors report on the long-term (6 and 10 years) outcome in terms of tic reduction, cognition, mood and side effects of medial thalamic deep brain stimulation in two previously described Tourette patients. The authors compared the outcome of two patients at 6 and 10 years after surgery with their preoperative status and after 8 months and 5 years of treatment, respectively. Standardised video recordings were scored by three independent investigators. Both patients underwent (neuro)psychological assessment at all time points of follow-up. Tic improvement observed at 5 years in patient 1 (90.1%) was maintained at 10 years (92.6%). In patient 2, the tic improvement at 8 months (82%) was slightly decreased at 6 years (78%). During follow-up, case 1 revealed no changes in cognition, but case 2 showed a decrease in verbal fluency and learning which was in line with his subjective reports. Case 2 showed a slight decrease in depression, but overall psychopathology was still high at 6 years after surgery with an increase in anger and aggression together with difficulties in social adaptation. Besides temporary hardware-related complications, no distressing adverse effects were observed. Bilateral thalamic stimulation may provide sustained tic benefit after at least 6 years, but to maximise overall outcome, attention is needed for postoperative psychosocial adaptation, already prior to surgery.
Horikawa, Tomoyasu; Kamitani, Yukiyasu
2017-01-01
Dreaming is generally thought to be generated by spontaneous brain activity during sleep with patterns common to waking experience. This view is supported by a recent study demonstrating that dreamed objects can be predicted from brain activity during sleep using statistical decoders trained with stimulus-induced brain activity. However, it remains unclear whether and how visual image features associated with dreamed objects are represented in the brain. In this study, we used a deep neural network (DNN) model for object recognition as a proxy for hierarchical visual feature representation, and DNN features for dreamed objects were analyzed with brain decoding of fMRI data collected during dreaming. The decoders were first trained with stimulus-induced brain activity labeled with the feature values of the stimulus image from multiple DNN layers. The decoders were then used to decode DNN features from the dream fMRI data, and the decoded features were compared with the averaged features of each object category calculated from a large-scale image database. We found that the feature values decoded from the dream fMRI data positively correlated with those associated with dreamed object categories at mid- to high-level DNN layers. Using the decoded features, the dreamed object category could be identified at above-chance levels by matching them to the averaged features for candidate categories. The results suggest that dreaming recruits hierarchical visual feature representations associated with objects, which may support phenomenal aspects of dream experience.
Kushibar, Kaisar; Valverde, Sergi; González-Villà, Sandra; Bernal, Jose; Cabezas, Mariano; Oliver, Arnau; Lladó, Xavier
2018-06-15
Sub-cortical brain structure segmentation in Magnetic Resonance Images (MRI) has attracted the interest of the research community for a long time as morphological changes in these structures are related to different neurodegenerative disorders. However, manual segmentation of these structures can be tedious and prone to variability, highlighting the need for robust automated segmentation methods. In this paper, we present a novel convolutional neural network based approach for accurate segmentation of the sub-cortical brain structures that combines both convolutional and prior spatial features for improving the segmentation accuracy. In order to increase the accuracy of the automated segmentation, we propose to train the network using a restricted sample selection to force the network to learn the most difficult parts of the structures. We evaluate the accuracy of the proposed method on the public MICCAI 2012 challenge and IBSR 18 datasets, comparing it with different traditional and deep learning state-of-the-art methods. On the MICCAI 2012 dataset, our method shows an excellent performance comparable to the best participant strategy on the challenge, while performing significantly better than state-of-the-art techniques such as FreeSurfer and FIRST. On the IBSR 18 dataset, our method also exhibits a significant increase in the performance with respect to not only FreeSurfer and FIRST, but also comparable or better results than other recent deep learning approaches. Moreover, our experiments show that both the addition of the spatial priors and the restricted sampling strategy have a significant effect on the accuracy of the proposed method. In order to encourage the reproducibility and the use of the proposed method, a public version of our approach is available to download for the neuroimaging community. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Optogenetically inspired deep brain stimulation: linking basic with clinical research.
Lüscher, Christian; Pollak, Pierre
2016-01-01
In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders. By extension, the technique has also been used to propose blueprints for innovative rational treatment of these diseases. The goal is to design manipulations that disrupt pathological circuit function or restore normal activity. This can be achieved by targeting specific projections in order to apply specific stimulation protocols validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a number of cases, specific forms of pathological synaptic plasticity have been implicated. For example, addictive drugs via strong increase of dopamine trigger a myriad of alterations of glutamate and γ-aminobutyric acid transmission, also called drug-evoked synaptic plasticity. This opens the way to the design of optogenetic reversal protocols, which might restore normal transmission with the hope to abolish the pathological behaviour. Several proof of principle studies for this approach have recently been published. However, for many reasons, optogenetics will not be translatable to human applications in the near future. Here, we argue that an intermediate step is novel deep brain stimulation (DBS) protocols that emulate successful optogenetic approaches in animal models. We provide a roadmap for a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand to novel indications.
NASA Astrophysics Data System (ADS)
Fontaine, Arjun K.; Kirchner, Matthew S.; Caldwell, John H.; Weir, Richard F.; Gibson, Emily A.
2018-02-01
Two-photon microscopy is a powerful tool of current scientific research, allowing optical visualization of structures below the surface of tissues. This is of particular value in neuroscience, where optically accessing regions within the brain is critical for the continued advancement in understanding of neural circuits. However, two-photon imaging at significant depths have typically used Ti:Sapphire based amplifiers that are prohibitively expensive and bulky. In this study, we demonstrate deep tissue two-photon imaging using a compact, inexpensive, turnkey operated Ytterbium fiber laser (Y-Fi, KM Labs). The laser is based on all-normal dispersion (ANDi) that provides short pulse durations and high pulse energies. Depth measurements obtained in ex vivo mouse cortex exceed those obtainable with standard two-photon microscopes using Ti:Sapphire lasers. In addition to demonstrating the capability of deep-tissue imaging in the brain, we investigated imaging depth in highly-scattering white matter with measurements in sciatic nerve showing limited optical penetration of heavily myelinated nerve tissue relative to grey matter.
A critical reflection on the technological development of deep brain stimulation (DBS)
Ineichen, Christian; Glannon, Walter; Temel, Yasin; Baumann, Christian R.; Sürücü, Oguzkan
2014-01-01
Since the translational research findings of Benabid and colleagues which partly led to their seminal paper regarding the treatment of mainly tremor-dominant Parkinson patients through thalamic high-frequency-stimulation (HFS) in 1987, we still struggle with identifying a satisfactory mechanistic explanation of the underlying principles of deep brain stimulation (DBS). Furthermore, the technological advance of DBS devices (electrodes and implantable pulse generators, IPG’s) has shown a distinct lack of dynamic progression. In light of this we argue that it is time to leave the paleolithic age and enter hellenistic times: the device-manufacturing industry and the medical community together should put more emphasis on advancing the technology rather than resting on their laurels. PMID:25278864
Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.
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
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
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
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.
Engineering the next generation of clinical deep brain stimulation technology.
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.
Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen
2018-05-01
The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.
Christiansen, Peter; Nielsen, Lars N; Steen, Kim A; Jørgensen, Rasmus N; Karstoft, Henrik
2016-11-11
Convolutional neural network (CNN)-based systems are increasingly used in autonomous vehicles for detecting obstacles. CNN-based object detection and per-pixel classification (semantic segmentation) algorithms are trained for detecting and classifying a predefined set of object types. These algorithms have difficulties in detecting distant and heavily occluded objects and are, by definition, not capable of detecting unknown object types or unusual scenarios. The visual characteristics of an agriculture field is homogeneous, and obstacles, like people, animals and other obstacles, occur rarely and are of distinct appearance compared to the field. This paper introduces DeepAnomaly, an algorithm combining deep learning and anomaly detection to exploit the homogenous characteristics of a field to perform anomaly detection. We demonstrate DeepAnomaly as a fast state-of-the-art detector for obstacles that are distant, heavily occluded and unknown. DeepAnomaly is compared to state-of-the-art obstacle detectors including "Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks" (RCNN). In a human detector test case, we demonstrate that DeepAnomaly detects humans at longer ranges (45-90 m) than RCNN. RCNN has a similar performance at a short range (0-30 m). However, DeepAnomaly has much fewer model parameters and (182 ms/25 ms =) a 7.28-times faster processing time per image. Unlike most CNN-based methods, the high accuracy, the low computation time and the low memory footprint make it suitable for a real-time system running on a embedded GPU (Graphics Processing Unit).
Christiansen, Peter; Nielsen, Lars N.; Steen, Kim A.; Jørgensen, Rasmus N.; Karstoft, Henrik
2016-01-01
Convolutional neural network (CNN)-based systems are increasingly used in autonomous vehicles for detecting obstacles. CNN-based object detection and per-pixel classification (semantic segmentation) algorithms are trained for detecting and classifying a predefined set of object types. These algorithms have difficulties in detecting distant and heavily occluded objects and are, by definition, not capable of detecting unknown object types or unusual scenarios. The visual characteristics of an agriculture field is homogeneous, and obstacles, like people, animals and other obstacles, occur rarely and are of distinct appearance compared to the field. This paper introduces DeepAnomaly, an algorithm combining deep learning and anomaly detection to exploit the homogenous characteristics of a field to perform anomaly detection. We demonstrate DeepAnomaly as a fast state-of-the-art detector for obstacles that are distant, heavily occluded and unknown. DeepAnomaly is compared to state-of-the-art obstacle detectors including “Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks” (RCNN). In a human detector test case, we demonstrate that DeepAnomaly detects humans at longer ranges (45–90 m) than RCNN. RCNN has a similar performance at a short range (0–30 m). However, DeepAnomaly has much fewer model parameters and (182 ms/25 ms =) a 7.28-times faster processing time per image. Unlike most CNN-based methods, the high accuracy, the low computation time and the low memory footprint make it suitable for a real-time system running on a embedded GPU (Graphics Processing Unit). PMID:27845717
Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation
Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.
2016-01-01
Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709
Deep brain stimulation for the treatment of Alzheimer disease and dementias.
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.
NASA Astrophysics Data System (ADS)
Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David
2005-04-01
Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.
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
Hosain, M D Kamal; Kouzani, Abbas Z; Tye, Susannah J; Abulseoud, Osama A; Amiet, Andrew; Galehdar, Amir; Kaynak, Akif; Berk, Michael
2014-01-01
Design of a rectangular spiral planar inverted-F antenna (PIFA) at 915 MHz for wireless power transmission applications is proposed. The antenna and rectifying circuitry form a rectenna, which can produce dc power from a distant radio frequency energy transmitter. The generated dc power is used to operate a low-power deep brain stimulation pulse generator. The proposed antenna has the dimensions of 10 mm [Formula: see text]12.5 mm [Formula: see text]1.5 mm and resonance frequency of 915 MHz with a measured bandwidth of 15 MHz at return loss of [Formula: see text]. A dielectric substrate of FR-4 of [Formula: see text] and [Formula: see text] with thickness of 1.5 mm is used for both antenna and rectifier circuit simulation and fabrication because of its availability and low cost. An L-section impedance matching circuit is used between the PIFA and voltage doubler rectifier. The impedance matching circuit also works as a low-pass filter for elimination of higher order harmonics. Maximum dc voltage at the rectenna output is 7.5 V in free space and this rectenna can drive a deep brain stimulation pulse generator at a distance of 30 cm from a radio frequency energy transmitter, which transmits power of 26.77 dBm.
Synofzik, M
2007-12-01
Through the rapid progress in neuropharmacology it seems to become possible to effectively improve our cognitive capacities and emotional states by easily applicable means. Moreover, deep-brain stimulation may allow an effective therapeutic option for those neurological and psychiatric diseases which still can not be sufficiently treated by pharmacological measures. So far, however, both the benefit and the harm of these techniques are only insufficiently understood by neuroscience and detailed ethical analyses are still missing. In this article ethical criteria and most recent empirical evidence are systematically brought together for the first time. This analysis shows that it is irrelevant for an ethical evaluation whether a drug or a brain-machine interface is categorized as "enhancement" or "treatment" or whether it changes "human nature". The only decisive criteria are whether the intervention (1.) benefits the patient, (2.) does not harm the patient and (3.) is desired by the patient. However, current empirical data in both fields, neuropharmacology and deep-brain stimulation are still too sparse to adequately evaluate these criteria. Moreover, the focus in both fields has been strongly misled by neglecting the distinction between "benefit" and "efficacy": In past years research and clinical practice have only focused on physiological effects, but not on the actual benefit to the patient.
Semi-Automated Trajectory Analysis of Deep Ballistic Penetrating Brain Injury
Folio, Les; Solomon, Jeffrey; Biassou, Nadia; Fischer, Tatjana; Dworzak, Jenny; Raymont, Vanessa; Sinaii, Ninet; Wassermann, Eric M.; Grafman, Jordan
2016-01-01
Background Penetrating head injuries (PHIs) are common in combat operations and most have visible wound paths on computed tomography (CT). Objective We assess agreement between an automated trajectory analysis-based assessment of brain injury and manual tracings of encephalomalacia on CT. Methods We analyzed 80 head CTs with ballistic PHI from the Institutional Review Board approved Vietnam head injury registry. Anatomic reports were generated from spatial coordinates of projectile entrance and terminal fragment location. These were compared to manual tracings of the regions of encephalomalacia. Dice’s similarity coefficients, kappa, sensitivities, and specificities were calculated to assess agreement. Times required for case analysis were also compared. Results Results show high specificity of anatomic regions identified on CT with semiautomated anatomical estimates and manual tracings of tissue damage. Radiologist’s and medical students’ anatomic region reports were similar (Kappa 0.8, t-test p < 0.001). Region of probable injury modeling of involved brain structures was sensitive (0.7) and specific (0.9) compared with manually traced structures. Semiautomated analysis was 9-fold faster than manual tracings. Conclusion Our region of probable injury spatial model approximates anatomical regions of encephalomalacia from ballistic PHI with time-saving over manual methods. Results show potential for automated anatomical reporting as an adjunct to current practice of radiologist/neurosurgical review of brain injury by penetrating projectiles. PMID:23707123
Finder, Stuart G; Bliton, Mark J; Gill, Chandler E; Davis, Thomas L; Konrad, Peter E; Charles, P David
2012-01-01
Central to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson's disease, since potential subjects will be Parkinson's patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses. As part of an expanded informed consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson's disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation. While the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as poten- tial benefit from enrolling. However, 91 percent also indicated helping other Parkinson's patients as motivation when considering whether or not to enroll. This combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects' preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson's sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed.
Programming Deep Brain Stimulation for Tremor and Dystonia: The Toronto Western Hospital Algorithms.
Picillo, Marina; Lozano, Andres M; Kou, Nancy; Munhoz, Renato Puppi; Fasano, Alfonso
2016-01-01
Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET) and dystonia. After surgery, a number of extensive programming sessions are performed, mainly relying on neurologist's personal experience as no programming guidelines have been provided so far, with the exception of recommendations provided by groups of experts. Finally, fewer information is available for the management of DBS in ET and dystonia compared with Parkinson's disease. Our aim is to review the literature on initial and follow-up DBS programming procedures for ET and dystonia and integrate the results with our current practice at Toronto Western Hospital (TWH) to develop standardized DBS programming protocols. We conducted a literature search of PubMed from inception to July 2014 with the keywords "balance", "bradykinesia", "deep brain stimulation", "dysarthria", "dystonia", "gait disturbances", "initial programming", "loss of benefit", "micrographia", "speech", "speech difficulties" and "tremor". Seventy-six papers were considered for this review. Based on the literature review and our experience at TWH, we refined three algorithms for management of ET, including: (1) initial programming, (2) management of balance and speech issues and (3) loss of stimulation benefit. We also depicted algorithms for the management of dystonia, including: (1) initial programming and (2) management of stimulation-induced hypokinesia (shuffling gait, micrographia and speech impairment). We propose five algorithms tailored to an individualized approach to managing ET and dystonia patients with DBS. We encourage the application of these algorithms to supplement current standards of care in 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.
Hemispheric dissociation of reward processing in humans: insights from deep brain stimulation.
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.
Guo, Xiaopeng; Zhang, Fa; Wu, Yue; Gao, Lu; Wang, Qiang; Wang, Zihao; Feng, Chenzhe; Yang, Yi; Xing, Bing; Xu, Zhiqin
2018-06-01
To explore coagulation function in patients with brain tumors before and after craniotomy and tumor resection and to analyze its correlation with deep vein thrombosis (DVT). This study enrolled 133 consecutive patients with brain tumors. Coagulation evaluation and limb venous ultrasonography were performed before and after surgery. Clinical characteristics and dynamic changes in coagulation parameters were recorded, and their correlations with DVT were analyzed. The incidence of postoperative DVT in patients with brain tumors was 10.5%. The average age of patients with DVT was older compared with patients without DVT (63.21 ± 11.21 years vs. 50.24 ± 11.95 years, P < 0.001), and the incidence of hepatitis B (21% vs. 4%, P = 0.035) was higher in patients with DVT compared with patients without DVT. D-dimer and fibrinogen were the most variable parameters during the perioperative period. In patients with DVT, D-dimer levels displayed a "zigzagging-rise" trend and were significantly higher than levels in patients without DVT. Platelet levels displayed a "first-descend-then-rise" trend and were significantly lower in patients with DVT on the second and third postoperative days. In patients with brain tumors, D-dimer and fibrinogen were elevated postoperatively, manifesting as hypercoagulability. Postoperative DVT was correlated with aging and hepatitis B. A "zigzagging-rise" trend of D-dimer and a "sharp-descent" trend of platelets in the early postoperative period might predict DVT in patients with brain tumors. Copyright © 2018 Elsevier Inc. All rights reserved.
Bilateral adaptive deep brain stimulation is effective in Parkinson's disease.
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/
Analysis of electrodes' placement and deformation in deep brain stimulation from medical images
NASA Astrophysics Data System (ADS)
Mehri, Maroua; Lalys, Florent; Maumet, Camille; Haegelen, Claire; Jannin, Pierre
2012-02-01
Deep brain stimulation (DBS) is used to reduce the motor symptoms such as rigidity or bradykinesia, in patients with Parkinson's disease (PD). The Subthalamic Nucleus (STN) has emerged as prime target of DBS in idiopathic PD. However, DBS surgery is a difficult procedure requiring the exact positioning of electrodes in the pre-operative selected targets. This positioning is usually planned using patients' pre-operative images, along with digital atlases, assuming that electrode's trajectory is linear. However, it has been demonstrated that anatomical brain deformations induce electrode's deformations resulting in errors in the intra-operative targeting stage. In order to meet the need of a higher degree of placement accuracy and to help constructing a computer-aided-placement tool, we studied the electrodes' deformation in regards to patients' clinical data (i.e., sex, mean PD duration and brain atrophy index). Firstly, we presented an automatic algorithm for the segmentation of electrode's axis from post-operative CT images, which aims to localize the electrodes' stimulated contacts. To assess our method, we applied our algorithm on 25 patients who had undergone bilateral STNDBS. We found a placement error of 0.91+/-0.38 mm. Then, from the segmented axis, we quantitatively analyzed the electrodes' curvature and correlated it with patients' clinical data. We found a positive significant correlation between mean curvature index of the electrode and brain atrophy index for male patients and between mean curvature index of the electrode and mean PD duration for female patients. These results help understanding DBS electrode' deformations and would help ensuring better anticipation of electrodes' placement.
Deep Brain Stimulation in Early Parkinson’s Disease: Enrollment Experience from a Pilot Trial
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
Okun, Michael S; Foote, Kelly D; Wu, Samuel S; Ward, Herbert E; Bowers, Dawn; Rodriguez, Ramon L; Malaty, Irene A; Goodman, Wayne K; Gilbert, Donald M; Walker, Harrison C; Mink, Jonathan W; Merritt, Stacy; Morishita, Takashi; Sanchez, Justin C
2013-01-01
To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. A university movement disorders center. Five patients with implanted DBS. A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. This study provides
A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo
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
Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U
2016-11-01
Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar
The epistemology of Deep Brain Stimulation and neuronal pathophysiology
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
State of the Art: Novel Applications for Deep Brain Stimulation.
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.
Effects of thalamic deep brain stimulation on spontaneous language production.
Ehlen, Felicitas; Vonberg, Isabelle; Kühn, Andrea A; Klostermann, Fabian
2016-08-01
The thalamus is thought to contribute to language-related processing, but specifications of this notion remain vague. An assessment of potential effects of thalamic deep brain stimulation (DBS) on spontaneous language may help to delineate respective functions. For this purpose, we analyzed spontaneous language samples from thirteen (six female / seven male) patients with essential tremor treated with DBS of the thalamic ventral intermediate nucleus (VIM) in their respective ON vs. OFF conditions. Samples were obtained from semi-structured interviews and examined on multidimensional linguistic levels. In the VIM-DBS ON condition, participants used a significantly higher proportion of paratactic as opposed to hypotactic sentence structures. This increase correlated negatively with the change in the more global cognitive score, which in itself did not change significantly. In conclusion, VIM-DBS appears to induce the use of a simplified syntactic structure. The findings are discussed in relation to concepts of thalamic roles in language-related cognitive behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.
Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study
NASA Astrophysics Data System (ADS)
Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans
2015-03-01
Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.
Donovan, Chris; Sweet, Jennifer; Eccher, Matthew; Megerian, Cliff; Semaan, Maroun; Murray, Gail; Miller, Jonathan
2015-12-01
Tinnitus is a source of considerable morbidity, and neuromodulation has been shown to be a potential treatment option. However, the location of the primary auditory cortex within Heschl gyrus in the temporal operculum presents challenges for targeting and electrode implantation. To determine whether anatomic targeting with intraoperative verification using evoked potentials can be used to implant electrodes directly into the Heschl gyrus (HG). Nine patients undergoing stereo-electroencephalogram evaluation for epilepsy were enrolled. HG was directly targeted on volumetric magnetic resonance imaging, and framed stereotaxy was used to implant an electrode parallel to the axis of the gyrus by using an oblique anterolateral-posteromedial trajectory. Intraoperative evoked potentials from auditory stimuli were recorded from multiple electrode contacts. Postoperatively, stimulation of each electrode was performed and participants were asked to describe the percept. Audiometric analysis was performed for 2 participants during subthreshold stimulation. Sounds presented to the contralateral and ipsilateral ears produced evoked potentials in HG electrodes in all participants intraoperatively. Stimulation produced a reproducible sensation of sound in all participants with perceived volume proportional to amplitude. Four participants reported distinct sounds when different electrodes were stimulated, with more medial contacts producing tones perceived as higher in pitch. Stimulation was not associated with adverse audiometric effects. There were no complications of electrode implantation. Direct anatomic targeting with physiological verification can be used to implant electrodes directly into primary auditory cortex. If deep brain stimulation proves effective for intractable tinnitus, this technique may be useful to assist with electrode implantation. DBS, deep brain stimulatorEEG, electroencephalographyHG, Heschl gyrus.
Deep brain stimulation can regulate arterial blood pressure in awake humans.
Green, Alexander L; Wang, Shouyan; Owen, Sarah L F; Xie, Kangning; Liu, Xuguang; Paterson, David J; Stein, John F; Bain, Peter G; Aziz, Tipu Z
2005-11-07
The periaqueductal grey matter is known to play a role in cardiovascular control in animals. Cardiovascular responses to electrical stimulation of the periventricular/periaqueductal grey matter were measured in 15 awake human study participants following implantation of deep brain stimulating electrodes for treatment of chronic pain. We found that stimulation of the ventral periventricular/periaqueductal grey matter caused a mean reduction in systolic blood pressure of 14.2+/-3.6 mmHg in seven patients and stimulation of the dorsal periventricular/periaqueductal grey matter caused a mean increase of 16.7+/-5.9 mmHg in six patients. A comparison between ventral and dorsal electrodes demonstrated significant differences (P<0.05). These changes were accompanied by analogous changes in diastolic blood pressure, pulse pressure, maximum dP/dt but not in the time interval between each R wave on the electrocardiogram.
Deep Sequencing to Identify the Causes of Viral Encephalitis
Chan, Benjamin K.; Wilson, Theodore; Fischer, Kael F.; Kriesel, John D.
2014-01-01
Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue. PMID:24699691
ERIC Educational Resources Information Center
Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; van Doorn, Jan
2013-01-01
Purpose: The purpose of the present study was to examine the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) pitch characteristics of connected speech in patients with Parkinson's disease (PD). Method: The authors evaluated 16 patients preoperatively and 12 months after DBS surgery. Eight…
Viaña, John Noel M; Vickers, James C; Cook, Mark J; Gilbert, Frederic
2017-08-01
The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention. Based on information from these reports and studies, we identify potential translational challenges of this approach and determine practical and ethical considerations for clinical trials, focusing on issues regarding selection criteria, trial design, and outcome evaluation. Based on initial results suggesting greater benefit for those with milder disease stage, we find it essential that participant expectations are carefully managed to avoid treatment disenchantment and/or frustration from participants and caregivers. Finally, we urge for collaboration between centers to establish proper clinical standards and to promote better trial results comparison. Copyright © 2017 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.
2014-06-01
Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.
Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R
2014-06-01
Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.
Delayed and lasting effects of deep brain stimulation on locomotion in Parkinson's disease
NASA Astrophysics Data System (ADS)
Beuter, Anne; Modolo, Julien
2009-06-01
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a variety of motor signs affecting gait, postural stability, and tremor. These symptoms can be improved when electrodes are implanted in deep brain structures and electrical stimulation is delivered chronically at high frequency (>100 Hz). Deep brain stimulation (DBS) onset or cessation affects PD signs with different latencies, and the long-term improvements of symptoms affecting the body axis and those affecting the limbs vary in duration. Interestingly, these effects have not been systematically analyzed and modeled. We compare these timing phenomena in relation to one axial (i.e., locomotion) and one distal (i.e., tremor) signs. We suggest that during DBS, these symptoms are improved by different network mechanisms operating at multiple time scales. Locomotion improvement may involve a delayed plastic reorganization, which takes hours to develop, whereas rest tremor is probably alleviated by an almost instantaneous desynchronization of neural activity in subcortical structures. Even if all PD patients develop both distal and axial symptoms sooner or later, current computational models of locomotion and rest tremor are separate. Furthermore, a few computational models of locomotion focus on PD and none exploring the effect of DBS was found in the literature. We, therefore, discuss a model of a neuronal network during DBS, general enough to explore the subcircuits controlling locomotion and rest tremor simultaneously. This model accounts for synchronization and plasticity, two mechanisms that are believed to underlie the two types of symptoms analyzed. We suggest that a hysteretic effect caused by DBS-induced plasticity and synchronization modulation contributes to the different therapeutic latencies observed. Such a comprehensive, generic computational model of DBS effects, incorporating these timing phenomena, should assist in developing a more efficient, faster, durable treatment of
Quinn, Emma J; Blumenfeld, Zack; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren A; Trager, Megan H; Hill, Bruce C; Kilbane, Camilla; Henderson, Jaimie M; Brontë-Stewart, Helen
2015-11-01
Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS. © 2015 International Parkinson and Movement Disorder Society.
Akata, Takashi; Setoguchi, Hidekazu; Shirozu, Kazuhiro; Yoshino, Jun
2007-06-01
It is essential to estimate the brain temperature of patients during deliberate deep hypothermia. Using jugular bulb temperature as a standard for brain temperature, we evaluated the accuracy and precision of 5 standard temperature monitoring sites (ie, pulmonary artery, nasopharynx, forehead deep-tissue, urinary bladder, and fingertip skin-surface tissue) during deep hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction. In 20 adult patients with thoracic aortic aneurysms, the 5 temperature monitoring sites were recorded every 1 minute during deep hypothermic (<20 degrees C) cardiopulmonary bypass. The accuracy was evaluated by the difference from jugular bulb temperature, and the precision was evaluated by its standard deviation, as well as by the correlation with jugular bulb temperature. Pulmonary artery temperature and jugular bulb temperature began to change immediately after the start of cooling or rewarming, closely matching each other, and the other temperatures lagged behind these two temperatures. During either situation, the accuracy of pulmonary artery temperature measurement (0.3 degrees C-0.5 degrees C) was much superior to the other measurements, and its precision (standard deviation of the difference from jugular bulb temperature = 1.5 degrees C-1.8 degrees C; correlation coefficient = 0.94-0.95) was also best among the measurements, with its rank order being pulmonary artery > or = nasopharynx > forehead > bladder > fingertip. However, the accuracy and precision of pulmonary artery temperature measurement was significantly impaired during and for several minutes after infusion of cold cardioplegic solution. Pulmonary artery temperature measurement is recommended to estimate brain temperature during deep hypothermic cardiopulmonary bypass, even if it is conducted with the sternum opened; however, caution needs to be exercised in interpreting its measurements during periods of the cardioplegic solution infusion.
Classification of CT brain images based on deep learning networks.
Gao, Xiaohong W; Hui, Rui; Tian, Zengmin
2017-01-01
While computerised tomography (CT) may have been the first imaging tool to study human brain, it has not yet been implemented into clinical decision making process for diagnosis of Alzheimer's disease (AD). On the other hand, with the nature of being prevalent, inexpensive and non-invasive, CT does present diagnostic features of AD to a great extent. This study explores the significance and impact on the application of the burgeoning deep learning techniques to the task of classification of CT brain images, in particular utilising convolutional neural network (CNN), aiming at providing supplementary information for the early diagnosis of Alzheimer's disease. Towards this end, three categories of CT images (N = 285) are clustered into three groups, which are AD, lesion (e.g. tumour) and normal ageing. In addition, considering the characteristics of this collection with larger thickness along the direction of depth (z) (~3-5 mm), an advanced CNN architecture is established integrating both 2D and 3D CNN networks. The fusion of the two CNN networks is subsequently coordinated based on the average of Softmax scores obtained from both networks consolidating 2D images along spatial axial directions and 3D segmented blocks respectively. As a result, the classification accuracy rates rendered by this elaborated CNN architecture are 85.2%, 80% and 95.3% for classes of AD, lesion and normal respectively with an average of 87.6%. Additionally, this improved CNN network appears to outperform the others when in comparison with 2D version only of CNN network as well as a number of state of the art hand-crafted approaches. As a result, these approaches deliver accuracy rates in percentage of 86.3, 85.6 ± 1.10, 86.3 ± 1.04, 85.2 ± 1.60, 83.1 ± 0.35 for 2D CNN, 2D SIFT, 2D KAZE, 3D SIFT and 3D KAZE respectively. The two major contributions of the paper constitute a new 3-D approach while applying deep learning technique to extract signature information
Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.
Koivu, Maija; Huotarinen, Antti; Scheperjans, Filip; Laakso, Aki; Kivisaari, Riku; Pekkonen, Eero
2018-05-30
To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.
2016-09-01
Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.
Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.
2016-01-01
Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought. PMID:27624437
Bar-Kochva, Irit
2011-01-01
Orthographies range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Two forms of script transcribe the Hebrew language: the shallow pointed script (with diacritics) and the deep unpointed script (without diacritics). This study was set out to examine whether the reading of these scripts evokes distinct brain activity. Preliminary results indicate distinct Event-related-potentials (ERPs). As an equivalent finding was absent when ERPs of non-orthographic stimuli with and without meaningless diacritics were compared, the results imply that print-specific aspects of processing account for the distinct activity elicited by the pointed and unpointed scripts.
Dr. Robert G. Heath: a controversial figure in the history of deep brain stimulation.
O'Neal, Christen M; Baker, Cordell M; Glenn, Chad A; Conner, Andrew K; Sughrue, Michael E
2017-09-01
The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.
Deep brain stimulation, brain maps and personalized medicine: lessons from the human genome project.
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.
Mechanisms and targets of deep brain stimulation in movement disorders.
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.
Stable microwave radiometry system for long term monitoring of deep tissue temperature
NASA Astrophysics Data System (ADS)
Stauffer, Paul R.; Rodriques, Dario B.; Salahi, Sara; Topsakal, Erdem; Oliveira, Tiago R.; Prakash, Aniruddh; D'Isidoro, Fabio; Reudink, Douglas; Snow, Brent W.; Maccarini, Paolo F.
2013-02-01
Background: There are numerous clinical applications for non-invasive monitoring of deep tissue temperature. We present the design and experimental performance of a miniature radiometric thermometry system for measuring volume average temperature of tissue regions located up to 5cm deep in the body. Methods: We constructed a miniature sensor consisting of EMI-shielded log spiral microstrip antenna with high gain onaxis and integrated high-sensitivity 1.35GHz total power radiometer with 500 MHz bandwidth. We tested performance of the radiometry system in both simulated and experimental multilayer phantom models of several intended clinical measurement sites: i) brown adipose tissue (BAT) depots within 2cm of the skin surface, ii) 3-5cm deep kidney, and iii) human brain underlying intact scalp and skull. The physical models included layers of circulating tissue-mimicking liquids controlled at different temperatures to characterize our ability to quantify small changes in target temperature at depth under normothermic surface tissues. Results: We report SAR patterns that characterize the sense region of a 2.6cm diameter receive antenna, and radiometric power measurements as a function of deep tissue temperature that quantify radiometer sensitivity. The data demonstrate: i) our ability to accurately track temperature rise in realistic tissue targets such as urine refluxed from prewarmed bladder into kidney, and 10°C drop in brain temperature underlying normothermic scalp and skull, and ii) long term accuracy and stability of +0.4°C over 4.5 hours as needed for monitoring core body temperature over extended surgery or monitoring effects of brown fat metabolism over an extended sleep/wake cycle. Conclusions: A non-invasive sensor consisting of 2.6cm diameter receive antenna and integral 1.35GHz total power radiometer has demonstrated sufficient sensitivity to track clinically significant changes in temperature of deep tissue targets underlying normothermic surface
Feinkohl, Insa; Flemming, Danny; Cress, Ulrike
2016-01-01
Background Laypeople frequently discuss medical research findings on Web-based platforms, but little is known about whether they grasp the tentativeness that is inherent in these findings. Potential influential factors involved in understanding medical tentativeness have hardly been assessed to date. Objective The research presented here aimed to examine the effects of personality factors and of other users’ previous contributions in a Web-based forum on laypeople’s understanding of the tentativeness of medical research findings, using the example of research on deep brain stimulation. Methods We presented 70 university students with an online news article that reported findings on applying deep brain stimulation as a novel therapeutic method for depression, which participants were unfamiliar with. In a randomized controlled experiment, we manipulated the forum such that the article was either accompanied by user comments that addressed the issue of tentativeness, by comments that did not address this issue, or the article was accompanied by no comments at all. Participants were instructed to write their own individual user comments. Their scientific literacy, epistemological beliefs, and academic self-efficacy were measured. The outcomes measured were perceived tentativeness and tentativeness addressed in the participants’ own comments. Results More sophisticated epistemological beliefs enhanced the perception of tentativeness (standardized β=.26, P=.034). Greater scientific literacy (stand. β=.25, P=.025) and greater academic self-efficacy (stand. β=.31, P=.007) were both predictors of a more extensive discussion of tentativeness in participants’ comments. When forum posts presented in the experiment addressed the issue of tentativeness, participants’ subsequent behavior tended to be consistent with what they had read in the forum, F 2,63=3.66; P=.049, ηp 2=.092. Conclusions Students’ understanding of the tentativeness of research findings on deep
ERIC Educational Resources Information Center
Knowles, Thea; Adams, Scott; Abeyesekera, Anita; Mancinelli, Cynthia; Gilmore, Greydon; Jog, Mandar
2018-01-01
Purpose: The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility. Method: Participants were tested under permutations of low, mid, and high STN-DBS frequency,…
Rejecting deep brain stimulation artefacts from MEG data using ICA and mutual information.
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.
Effect of deep brain stimulation on different speech subsystems in patients with multiple sclerosis.
Pützer, Manfred; Barry, William John; Moringlane, Jean Richard
2007-11-01
The effect of deep brain stimulation on articulation and phonation subsystems in seven patients with multiple sclerosis (MS) was examined. Production parameters in fast syllable-repetitions were defined and measured, and the phonation quality during vowel productions was analyzed. Speech material was recorded for patients (with and without stimulation) and for a group of healthy control speakers. With stimulation, the precision of glottal and supraglottal articulatory gestures is reduced, whereas phonation has a greater tendency to be hyperfunctional in comparison with the healthy control data. Different effects on the two speech subsystems are induced by electrical stimulation of the thalamus in patients with MS.
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
Haq, Ihtsham U; Foote, Kelly D; Goodman, Wayne G; Wu, Samuel S; Sudhyadhom, Atchar; Ricciuti, Nicola; Siddiqui, Mustafa S; Bowers, Dawn; Jacobson, Charles E; Ward, Herbert; Okun, Michael S
2011-01-01
We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over 2 years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes. Five patients experienced at least one smile response during testing. At higher voltages of stimulation, some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and p<0.0001 for left brain). In contrast, at contacts where smiles were not observed, mood was negatively correlated with voltage (p=0.0591 for right brain and p=0.0086 for left). Smile and laughter-inducing sites were located relatively medial, posterior, and deep in the ALIC-NA. The presence of stimulation induced laughter predicted improvement in OCD symptoms at 2 years. The higher the percentage of laugh conditions experienced in an individual patient, the greater the reduction in YBOCS (24 months, p=0.034). Other correlations between clinical outcomes and percent of smile/laugh conditions were not significant. These stimulation-induced behaviors were less frequently observed with 1 and 2-month postoperative test stimulation and were not observed at subsequent test stimulation sessions. Intraoperative stimulation-induced laughter may predict long-term OCD response to DBS. Identifying other potential response predictors for OCD will become increasingly important as more patients are
Haq, Ihtsham U; Foote, Kelly D; Goodman, Wayne G; Wu, Samuel S; Sudhyadhom, Atchar; Ricciutti, Nicola; Siddiqui, Mustafa S.; Bowers, Dawn; Jacobson, Charles E; Ward, Herbert; Okun, Michael S
2010-01-01
We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over two years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes. Five patients experienced at least one smile response during testing. At higher voltages of stimulation some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and p<0.0001 for left brain). In contrast, at contacts where smiles were not observed, mood was negatively correlated with voltage (p=0.0591 for right brain and p=0.0086 for left). Smile and laughter-inducing sites were located relatively medial, posterior, and deep in the ALIC-NA. The presence of stimulation induced laughter predicted improvement in OCD symptoms at two years. The higher the percentage of laugh conditions experienced in an individual patient, the greater the reduction in YBOCS (24 months, p=0.034). Other correlations between clinical outcomes and percent of smile/laugh conditions were not significant. These stimulation-induced behaviors were less frequently observed with one and two-month postoperative test stimulation and were not observed at subsequent test stimulation sessions. Intraoperative stimulation-induced laughter may predict long-term OCD response to DBS. Identifying other potential response predictors for OCD will become increasingly important as more
Deep learning for neuroimaging: a validation study.
Plis, Sergey M; Hjelm, Devon R; Salakhutdinov, Ruslan; Allen, Elena A; Bockholt, Henry J; Long, Jeffrey D; Johnson, Hans J; Paulsen, Jane S; Turner, Jessica A; Calhoun, Vince D
2014-01-01
Deep learning methods have recently made notable advances in the tasks of classification and representation learning. These tasks are important for brain imaging and neuroscience discovery, making the methods attractive for porting to a neuroimager's toolbox. Success of these methods is, in part, explained by the flexibility of deep learning models. However, this flexibility makes the process of porting to new areas a difficult parameter optimization problem. In this work we demonstrate our results (and feasible parameter ranges) in application of deep learning methods to structural and functional brain imaging data. These methods include deep belief networks and their building block the restricted Boltzmann machine. We also describe a novel constraint-based approach to visualizing high dimensional data. We use it to analyze the effect of parameter choices on data transformations. Our results show that deep learning methods are able to learn physiologically important representations and detect latent relations in neuroimaging data.
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.
Usability of therapy controllers in elderly patients with deep brain stimulation
2012-01-01
Background Technical devices are becoming more prevalent in society and also in medical care. Older adults need more support to learn new technologies than younger subjects. So far, no research has been done on the usability of patient controllers in deep brain stimulation in an elderly population. The aim of the study was to investigate the factors influencing the performance of elderly DBS patients with respect to usability aspects of Medtronic Access therapy controllers. Methods Time, mistakes and frequency of use of the controller were compared in 41 elderly DBS patients who prior to the study had already owned a therapy controller for more than six years. One group (n = 20, mean age = 66.4 years) was watching an instructional video and then completed practical assignments on a model implantable pulse generator (IPG). The other group (n = 21, mean age = 65.9 years) completed the tasks without having seen the video before. Any errors that patients made were documented and also corrected so that all of them received hands-on training. After six months all patients were re-evaluated on the dummy IPG in order to compare the effects of hands-on alone vs. video-based training combined with hands-on. Results The group that had seen the video before significantly outperformed the control group at both assessments with respect to number of errors. Both groups performed faster after six months compared to baseline and tend to use the controller more often than at baseline. Conclusion Our results indicate that elderly DBS patients who have been using the controller for several years still have various difficulties in operating the device. However, we also showed that age-specific training may improve the performance in older adults. In general, the design of DBS patient controllers should focus on the specific needs of the end-users. But as changes to medical devices take a long time to be implemented, video instructions with age-specific content plus hands-on training
Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection
Mertz, Jerome; Kim, Jinhyun
2010-01-01
It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast. PMID:20210471
Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection.
Mertz, Jerome; Kim, Jinhyun
2010-01-01
It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast.
Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection
NASA Astrophysics Data System (ADS)
Mertz, Jerome; Kim, Jinhyun
2010-01-01
It is well known that light-sheet illumination can enable optically sectioned wide-field imaging of macroscopic samples. However, the optical sectioning capacity of a light-sheet macroscope is undermined by sample-induced scattering or aberrations that broaden the thickness of the sheet illumination. We present a technique to enhance the optical sectioning capacity of a scanning light-sheet microscope by out-of-focus background rejection. The technique, called HiLo microscopy, makes use of two images sequentially acquired with uniform and structured sheet illumination. An optically sectioned image is then synthesized by fusing high and low spatial frequency information from both images. The benefits of combining light-sheet macroscopy and HiLo background rejection are demonstrated in optically cleared whole mouse brain samples, using both green fluorescent protein (GFP)-fluorescence and dark-field scattered light contrast.
Bardinet, Eric; Bhattacharjee, Manik; Dormont, Didier; Pidoux, Bernard; Malandain, Grégoire; Schüpbach, Michael; Ayache, Nicholas; Cornu, Philippe; Agid, Yves; Yelnik, Jérôme
2009-02-01
The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.
Chattha, P K; Greene, P E; Ramdhani, Ritesh A
2015-01-01
Pseudobulbar affect is a common symptom in neurodegenerative diseases and can also result from lesions in cortical, subcortical and brainstem regions. In Parkinson's disease (PD), pseudobulbar affect (PBA) can occur as a wearing off phenomenon, manifested usually as crying without emotionality. In addition, subthalamic (STN) deep brain stimulation (DBS) has been reported to induce PBA in PD patients with no prior history of such episodes. We present a case of inappropriate laughter lacking mirth as a levodopa OFF phenomenon in a patient with PD, whose laughter also worsened with STN-DBS in his non-medicated state. Levodopa ameliorated his PBA both with and without stimulation. The case demonstrates pseudobulbar laughter as a levodopa OFF phenomenon that is also exacerbated by STN-DBS.
Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.
Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho
2012-12-06
Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.
Medical Management of Parkinson's Disease after Initiation of Deep Brain Stimulation.
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.
Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation
Vidal, Jose; Ghovanloo, Maysam
2013-01-01
We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987
Fine-tuning convolutional deep features for MRI based brain tumor classification
NASA Astrophysics Data System (ADS)
Ahmed, Kaoutar B.; Hall, Lawrence O.; Goldgof, Dmitry B.; Liu, Renhao; Gatenby, Robert A.
2017-03-01
Prediction of survival time from brain tumor magnetic resonance images (MRI) is not commonly performed and would ordinarily be a time consuming process. However, current cross-sectional imaging techniques, particularly MRI, can be used to generate many features that may provide information on the patient's prognosis, including survival. This information can potentially be used to identify individuals who would benefit from more aggressive therapy. Rather than using pre-defined and hand-engineered features as with current radiomics methods, we investigated the use of deep features extracted from pre-trained convolutional neural networks (CNNs) in predicting survival time. We also provide evidence for the power of domain specific fine-tuning in improving the performance of a pre-trained CNN's, even though our data set is small. We fine-tuned a CNN initially trained on a large natural image recognition dataset (Imagenet ILSVRC) and transferred the learned feature representations to the survival time prediction task, obtaining over 81% accuracy in a leave one out cross validation.
Wu, Xi; Qiu, Yiqing; Simfukwe, Keith; Wang, Jiali; Chen, Jianchun
2017-01-01
Background Stimulation-induced transient nonmotor psychiatric symptoms (STPSs) are side effects following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. We designed algorithms which (1) determine the electrode contacts that induce STPSs and (2) provide a programming protocol to eliminate STPS and maintain the optimal motor functions. Our objective is to test the effectiveness of these algorithms. Materials and Methods 454 PD patients who underwent programming sessions after STN-DBS implantations were retrospectively analyzed. Only STPS patients were enrolled. In these patients, the contacts inducing STPS were found and the programming protocol algorithms used. Results Eleven patients were diagnosed with STPS. Of these patients, two had four episodes of crying, and two had four episodes of mirthful laughter. In one patient, two episodes of abnormal sense of spatial orientation were observed. Hallucination episodes were observed twice in one patient, while five patients recorded eight episodes of hypomania. There were no statistical differences between the UPDRS-III under the final stimulation parameter (without STPS) and previous optimum UPDRS-III under the STPSs (p = 1.000). Conclusion The flow diagram used for determining electrode contacts that induce STPS and the programming protocol employed in the treatment of these symptoms are effective. PMID:28894620
Kouzani, Abbas Z; Kale, Rajas P; Zarate-Garza, Pablo Patricio; Berk, Michael; Walder, Ken; Tye, Susannah J
2017-09-01
Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength [Formula: see text], width [Formula: see text], and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.
Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.
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.
Nagatani, Kimihiro; Takeuchi, Satoru; Feng, Dongxia; Mori, Kentaro; Day, J Diaz
2015-07-01
The high-definition exoscope (VITOM®, Karl Storz GmbH & Co., Tuttlingen, Germany) is a new equipment that can be used as an alternative to the operating microscope in neurosurgery. Several neurosurgeons have recently reported that the exoscope allows for long working distances and great depth of field. Herein, we review reported cases of exoscope use in neurosurgery. We also describe the advantages of the exoscope compared to the operating microscope and endoscope. Furthermore, we introduce a novel technique for microsurgical resection of deep brain lesions, in which the exoscope is used along with tubular retraction and frameless neuronavigation. Before the operation, neuronavigation is registered and the surgical trajectory is planned to avoid damaging the functional cortex and eloquent white matter tracts. By using intraoperative neuronavigation, the tubular retractor (NICO BrainPath®, NICO Corporation, Indianapolis, US), which is designed to split the white matter when gently inserted, is inserted transcortically into the brain to reach the lesion, along the preplanned trajectory. After insertion, the tubular retractor is fixed in place using a self-retaining arm. This creates a narrow corridor that enables the use of the exoscope (for optimum visualization), bimanual dissection technique, and long bayoneted surgical instruments. The large focal distance of the exoscope allows it to be placed sufficiently further away from the surgical site, permitting the passage of long surgical instruments under the scope. Although obtaining surgical access to deep-seated brain lesions is challenging, we consider that this technique facilitates a safe surgical approach for lesions in deep locations.
Recent advances in deep brain stimulation in psychiatric disorders.
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.
[Mental competence in the context of deep brain stimulation].
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.
Systems for deep brain stimulation: review of technical features.
Amon, A; Alesch, F
2017-09-01
The use of deep brain stimulation (DBS) is an important treatment option for movement disorders and other medical conditions. Today, three major manufacturers provide implantable systems for DBS. Although the underlying principle is basically the same for all available systems, the differences in the technical features vary considerably. This article outlines aspects regarding the technical features of DBS systems. The differences between voltage and current sources are addressed and their effect on stimulation is shown. To maintain clinical benefit and minimize side effects the stimulation field has to be adapted to the requirements of the patient. Shaping of the stimulation field can be achieved by the electrode design and polarity configuration. Furthermore, the electric signal consisting of stimulation rate, stimulation amplitude and pulse width affect the stimulation field. Interleaving stimulation is an additional concept, which permits improved treatment outcomes. Therefore, the electrode design, the polarity, the electric signal, and the concept of interleaving stimulation are presented. The investigated systems can be also categorized as rechargeable and non-rechargeable, which is briefly discussed. Options for interconnecting different system components from various manufacturers are presented. The present paper summarizes the technical features and their combination possibilities, which can have a major impact on the therapeutic effect.
Gronchi-Perrin, Aline; Viollier, Sarah; Ghika, Joseph; Combremont, Pierre; Villemure, Jean-Guy; Bogousslavsky, Julien; Burkhard, Pierre R; Vingerhoets, François
2006-09-01
We investigated the impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on quality of life (QOL) in patients with advanced Parkinson's disease, as self-assessed before and after surgery by completing the Parkinson's Disease Questionnaire (PDQ39). In addition to this prospective evaluation, we asked patients postoperatively to evaluate their preoperative QOL. In the prospective assessment, results showed that patients perceived a general improvement of QOL after the STN DBS. However, when evaluated retrospectively, they tended to overestimate their preoperative functioning, therefore obscuring the improvement found prospectively. This observation highlights the impact of the method used on obtained results when assessing the effects of STN DBS. (c) 2006 Movement Disorder Society.
Thalamic deep brain stimulation decelerates automatic lexical activation.
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.
Short circuit in deep brain stimulation.
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
Sun, Yulong; Ip, Philbert; Chakrabartty, Avijit
2017-09-03
Immunofluorescence is a common method used to visualize subcellular compartments and to determine the localization of specific proteins within a tissue sample. A great hindrance to the acquisition of high quality immunofluorescence images is endogenous autofluorescence of the tissue caused by aging pigments such as lipofuscin or by common sample preparation processes such as aldehyde fixation. This protocol describes how background fluorescence can be greatly reduced through photobleaching using white phosphor light emitting diode (LED) arrays prior to treatment with fluorescent probes. The broad-spectrum emission of white phosphor LEDs allow for bleaching of fluorophores across a range of emission peaks. The photobleaching apparatus can be constructed from off-the-shelf components at very low cost and offers an accessible alternative to commercially available chemical quenchers. A photobleaching pre-treatment of the tissue followed by conventional immunofluorescence staining generates images free of background autofluorescence. Compared to established chemical quenchers which reduced probe as well as background signals, photobleaching treatment had no effect on probe fluorescence intensity while it effectively reduced background and lipofuscin fluorescence. Although photobleaching requires more time for pre-treatment, higher intensity LED arrays may be used to reduce photobleaching time. This simple method can potentially be applied to a variety of tissues, particularly postmitotic tissues that accumulate lipofuscin such as the brain and cardiac or skeletal muscles.
Kuhn, Jens; Lenartz, Doris; Huff, Wolfgang; Lee, Sun-Hee; Koulousakis, Athanasios; Klosterkoetter, Joachim; Sturm, Volker
2009-01-01
Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient’s comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general. PMID:21686755
Fluoro jade-C staining in the assessment of brain injury after deep hypothermia circulatory arrest.
Wang, Ren; Ma, Wei-Guo; Gao, Guo-Dong; Mao, Qun-Xia; Zheng, Jun; Sun, Li-Zhong; Liu, Ying-Long
2011-02-04
To evaluate the efficacy of Fluoro Jade-C staining (FJC) in the assessment of brain injury after deep hypothermia circulatory arrest (DHCA). Six healthy adult miniature male pigs underwent DHCA, the rectal temperature was down to 18°C, circulation was stopped , circulatory arrest was maintained for 60 minutes. On postoperative day 1, perfusion-fixation was performed on brain tissue. Cerebral cortex, hippocampus, cerebellum were taken for sampling. FJC, hematoxylin-eosin staining (HE), nissl staining (NISSL), terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) were performed to detect the histological and pathological changes. Histological scores of all slices were ranked. Comparison between the FJC and other techniques was done by analysis of variance (ANOVA) according to histological scores. All animals survived the operation. On the cerebral cortex, in comparison of FJC between HE, NISSL and TUNEL, the p value was 0.90, 0.40, 0.16 respectively (p>0.05). On the hippocampus, the comparison of FJC with HE, NISSL and TUNEL had a p value of 0.12, 0.23, 0.62 respectively (p>0.05). On the cerebellum, in comparing FJC with HE, NISSL and TUNEL, the p value was 0.96, 0.77, 0.96 respectively (p>0.05). On representative regions, the results of FJC were in accordance with that of TUNEL, NISSL and HE. Furthermore, ascertainment of brain injury is easier with FJC. FJC is a reliable and convenient method to assess brain injury after DHCA. Copyright © 2010 Elsevier B.V. All rights reserved.
Naesström, Matilda; Blomstedt, Patric; Hariz, Marwan; Bodlund, Owe
2017-01-01
Background: Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. The number of implants worldwide is slowly increasing. Therefore, it is of importance to explore knowledge and concerns of this novel treatment among patients and their psychiatric healthcare contacts. This information is relevant for scientific professionals working with clinical studies for DBS for this indication. Especially, for future study designs and the creation of information targeting healthcare professionals and patients. The aim of this study was to explore the knowledge and concerns toward DBS among patients with OCD, psychiatrists, and cognitive behavioral therapists. Methods: The study was conducted through web-based surveys for the aimed target groups –psychiatrist, patients, and cognitive behavioral therapists. The surveys contained questions regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy. Results: The main source of information was from scientific sources among psychiatrists and psychotherapists. The patient's main source of information was the media. Common concerns among the groups included complications from surgery, anesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists, and ethical concerns among psychiatrists. Conclusion: There are challenges for DBS in OCD as identified by the participants of this study; source and quality of information, efficacy, potential adverse effects, and eligibility. In all of which the current evidence base still is limited. A broad research agenda is needed for studies going forward. PMID:29285414
NASA Astrophysics Data System (ADS)
McElcheran, Clare
Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In this thesis, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Three pTx coil configurations with 2-elements, 4-elements, and 8-elements, respectively, were investigated. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. Three cases were investigated to develop and evaluate this technique. First, a Proof-of-Concept study was performed to investigate the case of a simple, uniform cylindrical phantom with a straight, perfectly conducting wire. Second, a heterogeneous subject with bilateral, curved implanted wires was investigated. Finally, the third case investigated realistic patient lead-trajectories obtained from intra-operative CT scans. In all three cases, specific absorption rate (SAR), a metric used to quantify power deposition which results in heating, was reduced by over 90%. Maximal reduction in SAR was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the
Batra, Vinita; Guerin, Glenn F.; Goeders, Nicholas E.; Wilden, Jessica A.
2016-01-01
Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID:26863392
Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report.
Tamás, Gertrúd; Kovács, Norbert; Varga, Noémi Ágnes; Barsi, Péter; Erőss, Loránd; Molnár, Mária Judit; Balás, István
2016-01-01
We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Cui, Shaoguo; Mao, Lei; Jiang, Jingfeng; Liu, Chang; Xiong, Shuyu
2018-01-01
Brain tumors can appear anywhere in the brain and have vastly different sizes and morphology. Additionally, these tumors are often diffused and poorly contrasted. Consequently, the segmentation of brain tumor and intratumor subregions using magnetic resonance imaging (MRI) data with minimal human interventions remains a challenging task. In this paper, we present a novel fully automatic segmentation method from MRI data containing in vivo brain gliomas. This approach can not only localize the entire tumor region but can also accurately segment the intratumor structure. The proposed work was based on a cascaded deep learning convolutional neural network consisting of two subnetworks: (1) a tumor localization network (TLN) and (2) an intratumor classification network (ITCN). The TLN, a fully convolutional network (FCN) in conjunction with the transfer learning technology, was used to first process MRI data. The goal of the first subnetwork was to define the tumor region from an MRI slice. Then, the ITCN was used to label the defined tumor region into multiple subregions. Particularly, ITCN exploited a convolutional neural network (CNN) with deeper architecture and smaller kernel. The proposed approach was validated on multimodal brain tumor segmentation (BRATS 2015) datasets, which contain 220 high-grade glioma (HGG) and 54 low-grade glioma (LGG) cases. Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity were used as evaluation metrics. Our experimental results indicated that our method could obtain the promising segmentation results and had a faster segmentation speed. More specifically, the proposed method obtained comparable and overall better DSC values (0.89, 0.77, and 0.80) on the combined (HGG + LGG) testing set, as compared to other methods reported in the literature. Additionally, the proposed approach was able to complete a segmentation task at a rate of 1.54 seconds per slice.
Mao, Lei; Liu, Chang; Xiong, Shuyu
2018-01-01
Brain tumors can appear anywhere in the brain and have vastly different sizes and morphology. Additionally, these tumors are often diffused and poorly contrasted. Consequently, the segmentation of brain tumor and intratumor subregions using magnetic resonance imaging (MRI) data with minimal human interventions remains a challenging task. In this paper, we present a novel fully automatic segmentation method from MRI data containing in vivo brain gliomas. This approach can not only localize the entire tumor region but can also accurately segment the intratumor structure. The proposed work was based on a cascaded deep learning convolutional neural network consisting of two subnetworks: (1) a tumor localization network (TLN) and (2) an intratumor classification network (ITCN). The TLN, a fully convolutional network (FCN) in conjunction with the transfer learning technology, was used to first process MRI data. The goal of the first subnetwork was to define the tumor region from an MRI slice. Then, the ITCN was used to label the defined tumor region into multiple subregions. Particularly, ITCN exploited a convolutional neural network (CNN) with deeper architecture and smaller kernel. The proposed approach was validated on multimodal brain tumor segmentation (BRATS 2015) datasets, which contain 220 high-grade glioma (HGG) and 54 low-grade glioma (LGG) cases. Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity were used as evaluation metrics. Our experimental results indicated that our method could obtain the promising segmentation results and had a faster segmentation speed. More specifically, the proposed method obtained comparable and overall better DSC values (0.89, 0.77, and 0.80) on the combined (HGG + LGG) testing set, as compared to other methods reported in the literature. Additionally, the proposed approach was able to complete a segmentation task at a rate of 1.54 seconds per slice. PMID:29755716
Subthalamic nucleus deep brain stimulation improves deglutition in Parkinson's disease.
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
Ulanowski, Elizabeth A; Danzl, Megan M; Sims, Kara M
2017-01-01
There is a lack of evidence examining the role of physical therapy (PT) to address movement dysfunction for individuals with essential tremor (ET). A 61-year-old male with ET and prolonged bilateral deep brain stimulation (DBS) completed 14 sessions of outpatient PT that emphasized balance, functional movements, and proximal stability training with an integration of principles of body awareness training and visual motor coordination. Improvements were noted in all outcome measures. This report describes a novel PT approach that offers a promising means of improving functional mobility and balance while decreasing falls risk in patients with ET.
ERIC Educational Resources Information Center
Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia
2011-01-01
Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…
ERIC Educational Resources Information Center
Karlsson, Fredrik; Olofsson, Katarina; Blomstedt, Patric; Linder, Jan; Nordh, Erik; van Doorn, Jan
2014-01-01
Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…
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.
Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami
2018-05-01
Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.
Litvak, Vladimir; Eusebio, Alexandre; Jha, Ashwani; Oostenveld, Robert; Barnes, Gareth R; Penny, William D; Zrinzo, Ludvic; Hariz, Marwan I; Limousin, Patricia; Friston, Karl J; Brown, Peter
2010-05-01
Insight into how brain structures interact is critical for understanding the principles of functional brain architectures and may lead to better diagnosis and therapy for neuropsychiatric disorders. We recorded, simultaneously, magnetoencephalographic (MEG) signals and subcortical local field potentials (LFP) in a Parkinson's disease (PD) patient with bilateral deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). These recordings offer a unique opportunity to characterize interactions between the subcortical structures and the neocortex. However, high-amplitude artefacts appeared in the MEG. These artefacts originated from the percutaneous extension wire, rather than from the actual DBS electrode and were locked to the heart beat. In this work, we show that MEG beamforming is capable of suppressing these artefacts and quantify the optimal regularization required. We demonstrate how beamforming makes it possible to localize cortical regions whose activity is coherent with the STN-LFP, extract artefact-free virtual electrode time-series from regions of interest and localize cortical areas exhibiting specific task-related power changes. This furnishes results that are consistent with previously reported results using artefact-free MEG data. Our findings demonstrate that physiologically meaningful information can be extracted from heavily contaminated MEG signals and pave the way for further analysis of combined MEG-LFP recordings in DBS patients. 2009 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Rosnitskiy, P. B.; Gavrilov, L. R.; Yuldashev, P. V.; Sapozhnikov, O. A.; Khokhlova, V. A.
2017-09-01
A noninvasive ultrasound surgery method that relies on using multi-element focused phased arrays is being successfully used to destroy tumors and perform neurosurgical operations in deep structures of the human brain. However, several drawbacks that limit the possibilities of the existing systems in their clinical use have been revealed: a large size of the hemispherical array, impossibility of its mechanical movement relative to the patient's head, limited volume of dynamic focusing around the center of curvature of the array, and side effect of overheating skull. Here we evaluate the possibility of using arrays of smaller size and aperture angles to achieve shock-wave formation at the focus for thermal and mechanical ablation (histotripsy) of brain tissue taking into account current intensity limitations at the array elements. The proposed approach has potential advantages to mitigate the existing limitations and expand the possibilities of transcranial ultrasound surgery.
Paschali, Anna; Messinis, Lambros; Lyros, Epameinondas; Constantoyannis, Costas; Kefalopoulou, Zinovia; Lakiotis, Velissarios; Papathanasopoulos, Panagiotis; Vassilakos, Paulos
2009-11-01
In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. During all assessments patients were "on" standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings.
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.
Modelling Peri-Perceptual Brain Processes in a Deep Learning Spiking Neural Network Architecture.
Gholami Doborjeh, Zohreh; Kasabov, Nikola; Gholami Doborjeh, Maryam; Sumich, Alexander
2018-06-11
Familiarity of marketing stimuli may affect consumer behaviour at a peri-perceptual processing level. The current study introduces a method for deep learning of electroencephalogram (EEG) data using a spiking neural network (SNN) approach that reveals the complexity of peri-perceptual processes of familiarity. The method is applied to data from 20 participants viewing familiar and unfamiliar logos. The results support the potential of SNN models as novel tools in the exploration of peri-perceptual mechanisms that respond differentially to familiar and unfamiliar stimuli. Specifically, the activation pattern of the time-locked response identified by the proposed SNN model at approximately 200 milliseconds post-stimulus suggests greater connectivity and more widespread dynamic spatio-temporal patterns for familiar than unfamiliar logos. The proposed SNN approach can be applied to study other peri-perceptual or perceptual brain processes in cognitive and computational neuroscience.
Computer-Guided Deep Brain Stimulation Programming for Parkinson's Disease.
Heldman, Dustin A; Pulliam, Christopher L; Urrea Mendoza, Enrique; Gartner, Maureen; Giuffrida, Joseph P; Montgomery, Erwin B; Espay, Alberto J; Revilla, Fredy J
2016-02-01
Pilot study to evaluate computer-guided deep brain stimulation (DBS) programming designed to optimize stimulation settings using objective motion sensor-based motor assessments. Seven subjects (five males; 54-71 years) with Parkinson's disease (PD) and recently implanted DBS systems participated in this pilot study. Within two months of lead implantation, the subject returned to the clinic to undergo computer-guided programming and parameter selection. A motion sensor was placed on the index finger of the more affected hand. Software guided a monopolar survey during which monopolar stimulation on each contact was iteratively increased followed by an automated assessment of tremor and bradykinesia. After completing assessments at each setting, a software algorithm determined stimulation settings designed to minimize symptom severities, side effects, and battery usage. Optimal DBS settings were chosen based on average severity of motor symptoms measured by the motion sensor. Settings chosen by the software algorithm identified a therapeutic window and improved tremor and bradykinesia by an average of 35.7% compared with baseline in the "off" state (p < 0.01). Motion sensor-based computer-guided DBS programming identified stimulation parameters that significantly improved tremor and bradykinesia with minimal clinician involvement. Automated motion sensor-based mapping is worthy of further investigation and may one day serve to extend programming to populations without access to specialized DBS centers. © 2015 International Neuromodulation Society.
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
Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.
Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D
2015-11-01
This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.
Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation
Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.
2015-01-01
This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727
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.
Hirai, Yasuharu; Nishino, Eri
2015-01-01
Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950
Hirai, Yasuharu; Nishino, Eri; Ohmori, Harunori
2015-06-01
Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. Copyright © 2015 the American Physiological Society.
FDTD analysis of a noninvasive hyperthermia system for brain tumors
2012-01-01
Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors. PMID:22891953
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.
Deep brain stimulation for the treatment of childhood dystonic cerebral palsy.
Keen, Joseph R; Przekop, Allison; Olaya, Joffre E; Zouros, Alexander; Hsu, Frank P K
2014-12-01
Deep brain stimulation (DBS) for dystonic cerebral palsy (CP) has rarely been reported, and its efficacy, though modest when compared with that for primary dystonia, remains unclear, especially in the pediatric population. The authors present a small series of children with dystonic CP who underwent bilateral pallidal DBS, to evaluate the treatment's efficacy and safety in the pediatric dystonic CP population. The authors conducted a retrospective review of patients (under the age of 18 years) with dystonic CP who had undergone DBS of the bilateral globus pallidus internus between 2010 and 2012. Two of the authors independently assessed outcomes using the Barry-Albright Dystonia Scale (BADS) and the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M). Five children were diagnosed with dystonic CP due to insults occurring before the age of 1 year. Mean age at surgery was 11 years (range 8-17 years), and the mean follow-up was 26.6 months (range 2-42 months). The mean target position was 20.6 mm lateral to the midcommissural point. The mean preoperative and postoperative BADS scores were 23.8 ± 4.9 (range 18.5-29.0) and 20.0 ± 5.5 (range 14.5-28.0), respectively, with a mean overall percent improvement of 16.0% (p = 0.14). The mean preoperative and postoperative BFMDRS-M scores were 73.3 ± 26.6 (range 38.5-102.0) and 52.4 ± 21.5 (range 34.0-80.0), respectively, with a mean overall percent improvement of 28.5% (p = 0.10). Those stimulated at least 23 months (4 patients) improved 18.3% (p = 0.14) on the BADS and 30.5% (p = 0.07) on the BFMDRS-M. The percentage improvement per body region yielded conflicting results between rating scales; however, BFMDRS-M scores for speech showed some of the greatest improvements. Two patients required hardware removal (1 complete system, 1 unilateral electrode) within 4 months after implantation because of infections that resolved with antibiotics. All postoperative dystonia rating scale scores improved with pallidal
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
Resendez, Shanna L.; Jennings, Josh H.; Ung, Randall L.; Namboodiri, Vijay Mohan K.; Zhou, Zhe Charles; Otis, James M.; Nomura, Hiroshi; McHenry, Jenna A.; Kosyk, Oksana; Stuber, Garret D.
2016-01-01
Genetically encoded calcium indicators for visualizing dynamic cellular activity have greatly expanded our understanding of the brain. However, due to light scattering properties of the brain as well as the size and rigidity of traditional imaging technology, in vivo calcium imaging has been limited to superficial brain structures during head fixed behavioral tasks. This limitation can now be circumvented by utilizing miniature, integrated microscopes in conjunction with an implantable microendoscopic lens to guide light into and out of the brain, thus permitting optical access to deep brain (or superficial) neural ensembles during naturalistic behaviors. Here, we describe procedural steps to conduct such imaging studies using mice. However, we anticipate the protocol can be easily adapted for use in other small vertebrates. Successful completion of this protocol will permit cellular imaging of neuronal activity and the generation of data sets with sufficient statistical power to correlate neural activity with stimulus presentation, physiological state, and other aspects of complex behavioral tasks. This protocol takes 6–11 weeks to complete. PMID:26914316
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.
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
Swallowing Quality of Life After Zona Incerta Deep Brain Stimulation.
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.
Mohammed, Ameer; Zamani, Majid; Bayford, Richard; Demosthenous, Andreas
2017-12-01
In Parkinson's disease (PD), on-demand deep brain stimulation is required so that stimulation is regulated to reduce side effects resulting from continuous stimulation and PD exacerbation due to untimely stimulation. Also, the progressive nature of PD necessitates the use of dynamic detection schemes that can track the nonlinearities in PD. This paper proposes the use of dynamic feature extraction and dynamic pattern classification to achieve dynamic PD detection taking into account the demand for high accuracy, low computation, and real-time detection. The dynamic feature extraction and dynamic pattern classification are selected by evaluating a subset of feature extraction, dimensionality reduction, and classification algorithms that have been used in brain-machine interfaces. A novel dimensionality reduction technique, the maximum ratio method (MRM) is proposed, which provides the most efficient performance. In terms of accuracy and complexity for hardware implementation, a combination having discrete wavelet transform for feature extraction, MRM for dimensionality reduction, and dynamic k-nearest neighbor for classification was chosen as the most efficient. It achieves a classification accuracy of 99.29%, an F1-score of 97.90%, and a choice probability of 99.86%.
Deep brain stimulation with a pre-existing cochlear implant: Surgical technique and outcome.
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.
Forster, Marie-Therese; Hoecker, Alexander Claudius; Kang, Jun-Suk; Quick, Johanna; Seifert, Volker; Hattingen, Elke; Hilker, Rüdiger; Weise, Lutz Martin
2015-06-01
Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures. To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking. Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift. Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation. The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.
Müller, Ulf J; Truebner, Kurt; Schiltz, Kolja; Kuhn, Jens; Mawrin, Christian; Dobrowolny, Henrik; Bernstein, Hans-Gert; Bogerts, Bernhard; Steiner, Johann
2015-12-01
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is increasingly investigated in neuropsychiatric disorders. DBS requires computer-assisted 3D planning to implant the stimulation electrode precisely. Recently, there has been a debate about the true dimensions of NAc in healthy as well as in mentally ill individuals. Knowing its true dimensions in different neuropsychiatric disorders may improve even more precise targeting of NAc for therapeutic DBS. Volumes of NAc of heroin addicts (n = 14) and healthy controls (n = 12) were calculated by using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1478.85 ± 62.34 vs. mean 1352.38 ± 103.24 cm(3)), as the heroin group was more than 10 years younger (p = 0.001). However, the mean volume of the NAc in heroin addicts was smaller than in controls (0.528 ± 0.166 vs. 0.623 ± 0.196 cm(3); p = 0.019). This group effect did not significantly differ between the hemispheres. When assessed separately, left-hemispheric NAc volume was 15 % lower (p = 0.020), while right-hemispheric NAc volume was 16 % lower (p = 0.047) in the heroin-addicted group compared to controls. Based on these diagnosis-related differences, we believe it is important to further analyze NAc volumes in different psychiatric disorders to further improve precise targeting and electrode placement.
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.
Cognitive functioning in psychiatric disorders following deep brain stimulation.
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.
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.
Self-guided training for deep brain stimulation planning using objective assessment.
Holden, Matthew S; Zhao, Yulong; Haegelen, Claire; Essert, Caroline; Fernandez-Vidal, Sara; Bardinet, Eric; Ungi, Tamas; Fichtinger, Gabor; Jannin, Pierre
2018-04-04
Deep brain stimulation (DBS) is an increasingly common treatment for neurodegenerative diseases. Neurosurgeons must have thorough procedural, anatomical, and functional knowledge to plan electrode trajectories and thus ensure treatment efficacy and patient safety. Developing this knowledge requires extensive training. We propose a training approach with objective assessment of neurosurgeon proficiency in DBS planning. To assess proficiency, we propose analyzing both the viability of the planned trajectory and the manner in which the operator arrived at the trajectory. To improve understanding, we suggest a self-guided training course for DBS planning using real-time feedback. To validate the proposed measures of proficiency and training course, two experts and six novices followed the training course, and we monitored their proficiency measures throughout. At baseline, experts planned higher quality trajectories and did so more efficiently. As novices progressed through the training course, their proficiency measures increased significantly, trending toward expert measures. We developed and validated measures which reliably discriminate proficiency levels. These measures are integrated into a training course, which quantitatively improves trainee performance. The proposed training course can be used to improve trainees' proficiency, and the quantitative measures allow trainees' progress to be monitored.
Delbeke, Jean; Hoffman, Luis; Mols, Katrien; Braeken, Dries; Prodanov, Dimiter
2017-01-01
Deep Brain Stimulation (DBS) has evolved into a well-accepted add-on treatment for patients with severe Parkinsons disease as well as for other chronic neurological conditions. The focal action of electrical stimulation can yield better responses and it exposes the patient to fewer side effects compared to pharmaceuticals distributed throughout the body toward the brain. On the other hand, the current practice of DBS is hampered by the relatively coarse level of neuromodulation achieved. Optogenetics, in contrast, offers the perspective of much more selective actions on the various physiological structures, provided that the stimulated cells are rendered sensitive to the action of light. Optogenetics has experienced tremendous progress since its first in vivo applications about 10 years ago. Recent advancements of viral vector technology for gene transfer substantially reduce vector-associated cytotoxicity and immune responses. This brings about the possibility to transfer this technology into the clinic as a possible alternative to DBS and neuromodulation. New paths could be opened toward a rich panel of clinical applications. Some technical issues still limit the long term use in humans but realistic perspectives quickly emerge. Despite a rapid accumulation of observations about patho-physiological mechanisms, it is still mostly serendipity and empiric adjustments that dictate clinical practice while more efficient logically designed interventions remain rather exceptional. Interestingly, it is also very much the neuro technology developed around optogenetics that offers the most promising tools to fill in the existing knowledge gaps about brain function in health and disease. The present review examines Parkinson's disease and refractory epilepsy as use cases for possible optogenetic stimulation therapies. PMID:29311765
Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras
2016-07-01
OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional
Chabardès, Stéphan; Carron, Romain; Seigneuret, Eric; Torres, Napoleon; Goetz, Laurent; Krainik, Alexandre; Piallat, Brigitte; Pham, Pascale; David, Olivier; Giraud, Pierrick; Benabid, Alim Louis
2016-12-01
The third ventricle (3rd V) is surrounded by centers related to satiety, homeostasis, hormones, sleep, memory, and pain. Stimulation of the wall of the 3rd V could be useful to treat disorders related to dysfunction of the hypothalamus. To assess safety and efficacy of endoventricular electrical stimulation of the hypothalamus using a floating deep brain stimulation (DBS) lead laid on the floor of the 3rd V to treat refractory cluster headaches (CH). Seven patients, aged 24 to 60 years, experiencing chronic CH (mean chronic duration 5.8 ± 2.5 years) were enrolled in this pilot, prospective, open study assessing the safety and potential efficacy of chronic DBS of the 3rd V. Number of attacks was collected during baseline and was compared with those occurring at 3, 6, and 12 months postoperation. Any side effects that occurred during or after surgery were reported. Effect on mood was assessed using the Hospital Anxiety and Depression scale during baseline and at 6 and 12 months postoperation. Insertion of the lead into the posterior 3rd V and chronic stimulation was feasible and safe in all patients. The voltage ranged from 0.9 to 2.3 volts. The most common side effect was transient trembling vision during stimulation. At 12 months, 3 of 7 patients were pain free, 2 had 90% improvement, 1 of 7 had 75% improvement, and 1 of 7 was not significantly improved. This proof of concept demonstrates the feasibility, safety, and potential efficacy of 3rd V DBS using an endoventricular road that could be applied to treat various diseases involving hypothalamic areas. CCH, chronic cluster headacheCH, cluster headacheDBS, deep brain stimulationHAD, hospital anxiety depressionONS, occipital nerve stimulationPAG, periaqueductal gray matterPH, posterior hypothalamusPVG, periventricular gray matter3rd V, third ventricle.
Deep Brain Stimulation for Parkinson's Disease
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Golestanirad, Laleh; Elahi, Behzad; Graham, Simon J; Das, Sunit; Wald, Lawrence L
2016-01-01
Pedunculopontine nucleus (PPN) has complex reciprocal connections with basal ganglia, especially with internal globus pallidus and substantia nigra, and it has been postulated that PPN stimulation may improve gait instability and freezing of gait. In this meta-analysis, we will assess the evidence for PPN deep brain stimulation in treatment of gait and motor abnormalities especially focusing on Parkinson disease patients. PubMed and Scopus electronic databases were searched for related studies published before February 2014. Medline (1966-2014), Embase (1974-2010), CINAHL, Web of Science, Scopus bibliographic, and Google Scholar databases (1960-2014) were also searched for studies investigating effect of PPN deep brain stimulation in treatment of postural and postural instability and total of ten studies met the inclusion criteria for this analysis. Our findings showed a significant improvement in postural instability (p<0.001) and motor symptoms of Parkinson disease on and off medications (p<0.05), but failed to show improvement in freezing of gait. Despite significant improvement in postural instability observed in included studies, evidence from current literature is not sufficient to generalize these findings to the majority of patients.
Deep Brain Stimulation for Dystonia: A Novel Perspective on the Value of Genetic Testing
Jinnah, H. A.; Alterman, Ron; Klein, Christine; Krauss, Joachim K.; Moro, Elena; Vidailhet, Marie; Raike, Robert
2017-01-01
The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal movements and postures. There are many different clinical manifestations and underlying causes. Deep brain stimulation (DBS) provides an effect treatment, but outcomes can vary considerably among the different subtypes of dystonia. Several variables are thought to contribute to this variation including age of onset and duration of dystonia, specific characteristics of the dystonic movements, location of stimulation and stimulator settings, and others. The potential contributions of genetic factors have received little attention. In this review, we summarize evidence that some of the variation in DBS outcomes for dystonia is due to genetic factors. The evidence suggests that more methodical genetic testing may provide useful information in the assessment of potential surgical candidates, and in advancing our understanding of the biological mechanisms that influence DBS outcomes. PMID:28160152
2011-01-01
Stuttering is a speech disorder with disruption of verbal fluency which is occasionally present in patients with Parkinson's disease (PD). Long-term medical management of PD is frequently complicated by fluctuating motor functions and dyskinesias. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment of motor fluctuations and is the most common surgical procedure in PD. Here we report the re-occurrence and aggravation of stuttering following STN-DBS in two male patients treated for advanced PD. In both patients the speech fluency improved considerably when the neurostimulator was turned off, indicating that stuttering aggravation was related to neurostimulation of the STN itself, its afferent or efferent projections and/or to structures localized in the immediate proximity. This report supports previous studies demonstrating that lesions of the basal ganglia-thalamocortical motor circuit, including the STN, is involved in the development of stuttering. In advanced PD STN-DBS is generally an effective and safe treatment. However, patients with PD and stuttering should be informed about the risk of aggravated symptoms following surgical therapy. PMID:21477305
Thalamic deep brain stimulation for writer's cramp.
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
Swann, Nicole; Poizner, Howard; Houser, Melissa; Gould, Sherrie; Greenhouse, Ian; Cai, Weidong; Strunk, Jon; George, Jobi; Aron, Adam R
2011-01-01
Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (~16-20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's Disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right-lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally-connected, functional, circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basal ganglia circuit. PMID:21490213
Lucas-Neto, Lia; Reimão, Sofia; Oliveira, Edson; Rainha-Campos, Alexandre; Sousa, João; Nunes, Rita G; Gonçalves-Ferreira, António; Campos, Jorge G
2015-07-01
The human nucleus accumbens (Acc) has become a target for deep brain stimulation (DBS) in some neuropsychiatric disorders. Nonetheless, even with the most recent advances in neuroimaging it remains difficult to accurately delineate the Acc and closely related subcortical structures, by conventional MRI sequences. It is our purpose to perform a MRI study of the human Acc and to determine whether there are reliable anatomical landmarks that enable the precise location and identification of the nucleus and its core/shell division. For the Acc identification and delineation, based on anatomical landmarks, T1WI, T1IR and STIR 3T-MR images were acquired in 10 healthy volunteers. Additionally, 32-direction DTI was obtained for Acc segmentation. Seed masks for the Acc were generated with FreeSurfer and probabilistic tractography was performed using FSL. The probability of connectivity between the seed voxels and distinct brain areas was determined and subjected to k-means clustering analysis, defining 2 different regions. With conventional T1WI, the Acc borders are better defined through its surrounding anatomical structures. The DTI color-coded vector maps and IR sequences add further detail in the Acc identification and delineation. Additionally, using probabilistic tractography it is possible to segment the Acc into a core and shell division and establish its structural connectivity with different brain areas. Advanced MRI techniques allow in vivo delineation and segmentation of the human Acc and represent an additional guiding tool in the precise and safe target definition for DBS. © 2015 International Neuromodulation Society.
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
Konrad, Peter E.; Neimat, Joseph S.; Yu, Hong; Kao, Chris C.; Remple, Michael S.; D'Haese, Pierre-François; Dawant, Benoit M.
2011-01-01
Background The microTargeting™ platform (MTP) stereotaxy system (FHC Inc., Bowdoin, Me., USA) was FDA approved in 2001 utilizing rapid-prototyping technology to create custom platforms for human stereotaxy procedures. It has also been called the STarFix (surgical targeting fixture) system since it is based on the concept of a patient- and procedure-specific surgical fixture. This is an alternative stereotactic method by which planned trajectories are incorporated into custom-built, miniature stereotactic platforms mounted onto bone fiducial markers. Our goal is to report the clinical experience with this system over a 6-year period. Methods We present the largest reported series of patients who underwent deep brain stimulation (DBS) implantations using customized rapidly prototyped stereotactic frames (MTP). Clinical experience and technical features for the use of this stereotactic system are described. Final lead location analysis using postoperative CT was performed to measure the clinical accuracy of the stereotactic system. Results Our series included 263 patients who underwent 284 DBS implantation surgeries at one institution over a 6-year period. The clinical targeting error without accounting for brain shift in this series was found to be 1.99 mm (SD 0.9). Operating room time was reduced through earlier incision time by 2 h per case. Conclusion Customized, miniature stereotactic frames, namely STarFix platforms, are an acceptable and efficient alternative method for DBS implantation. Its clinical accuracy and outcome are comparable to those associated with traditional stereotactic frame systems. PMID:21160241
Deep Brain Stimulation, Continuity over Time, and the True Self.
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.
Deep brain stimulation: a return journey from psychiatry to neurology.
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.
Barriers to investigator-initiated deep brain stimulation and device research
Malone, Donald; Okun, Michael S.; Booth, Joan; Machado, Andre G.
2014-01-01
The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients. PMID:24670888
Safonova, O A; Popova, T N; Kryl'skii, D V
2016-01-01
It was studied the total antioxidant activity, content of primary lipid peroxidation (LPO) products and reduced glutathione, and the activity of glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase in rat tissues under phenylethyl biguanide (phenfor- min) action on the background of experimental brain ischemia/reperfusion development. It is stablished the analyzed parameters, increasing under ischemia/reperfusion conditions in the brain and blood serum of animals, exhibit a decrease upon the introduction of this biguanide derivative. The obtained data can be explained by a decrease in degree of mobilization of the antioxidant system--in particular, of its glutathione chain--in the pathologic state. Hence, there is a need in NADPH supply for the system functioning compared with the pathology. Thus, phenylethyl biguanide demonstrates its antioxidant and protective properties under oxidative stress development that is accompanied by accumulation of the products of free radical oxidation of biomolecules during the ischemic brain injury.
A Right Brain/Left Brain Model of Acting.
ERIC Educational Resources Information Center
Bowlen, Clark
Using current right brain/left brain research, this paper develops a model that explains acting's underlying quality--the actor is both himself and the character. Part 1 presents (1) the background of the right brain/left brain theory, (2) studies showing that propositional communication is a left hemisphere function while affective communication…
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
Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.
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.
Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat
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
Sustained deep-tissue pain alters functional brain connectivity.
Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly
2013-08-01
Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity. Copyright © 2013 International Association for the Study of Pain. Published by
Complications of deep brain stimulation: a collective review.
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
Sustained deep-tissue pain alters functional brain connectivity
Kim, Jieun; Loggia, Marco L.; Edwards, Robert; Wasan, Ajay D.; Gollub, Randy L.; Napadow, Vitaly
2013-01-01
Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically-relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, fronto-parietal control and default mode networks; SMN, SLN, DAN, FCN and DMN) was evaluated with functional-connectivity MRI, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable with no significant changes of subjects’ pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala, was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to inter-individual differences in pain sensitivity. PMID:23718988
NASA Astrophysics Data System (ADS)
Wei, Xuefeng F.; Grill, Warren M.
2005-12-01
Deep brain stimulation (DBS) electrodes are designed to stimulate specific areas of the brain. The most widely used DBS electrode has a linear array of 4 cylindrical contacts that can be selectively turned on depending on the placement of the electrode and the specific area of the brain to be stimulated. The efficacy of DBS therapy can be improved by localizing the current delivery into specific populations of neurons and by increasing the power efficiency through a suitable choice of electrode geometrical characteristics. We investigated segmented electrode designs created by sectioning each cylindrical contact into multiple rings. Prototypes of these designs, made with different materials and larger dimensions than those of clinical DBS electrodes, were evaluated in vitro and in simulation. A finite element model was developed to study the effects of varying the electrode characteristics on the current density and field distributions in an idealized electrolytic medium and in vitro experiments were conducted to measure the electrode impedance. The current density over the electrode surface increased towards the edges of the electrode, and multiple edges increased the non-uniformity of the current density profile. The edge effects were more pronounced over the end segments than over the central segments. Segmented electrodes generated larger magnitudes of the second spatial difference of the extracellular potentials, and thus required lower stimulation intensities to achieve the same level of neuronal activation as solid electrodes. For a fixed electrode conductive area, increasing the number of segments (edges) decreased the impedance compared to a single solid electrode, because the average current density over the segments increased. Edge effects played a critical role in determining the current density distributions, neuronal excitation patterns, and impedance of cylindrical electrodes, and segmented electrodes provide a means to increase the efficiency of DBS.
Speed effects of deep brain stimulation for Parkinson's disease.
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.
Association of Deep Brain Stimulation Washout Effects With Parkinson Disease Duration
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
Kuenzel, Wayne J; Kang, Seong W; Zhou, Z Jimmy
2015-04-01
In the eyes of mammals, specialized photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGC) have been identified that sense photoperiodic or daylight exposure, providing them over time with seasonal information. Detectors of photoperiods are critical in vertebrates, particularly for timing the onset of reproduction each year. In birds, the eyes do not appear to monitor photoperiodic information; rather, neurons within at least 4 different brain structures have been proposed to function in this capacity. Specialized neurons, called deep brain photoreceptors (DBP), have been found in the septum and 3 hypothalamic areas. Within each of the 4 brain loci, one or more of 3 unique photopigments, including melanopsin, neuropsin, and vertebrate ancient opsin, have been identified. An experiment was designed to characterize electrophysiological responses of neurons proposed to be avian DBP following light stimulation. A second study used immature chicks raised under short-day photoperiods and transferred to long day lengths. Gene expression of photopigments was then determined in 3 septal-hypothalamic regions. Preliminary electrophysiological data obtained from patch-clamping neurons in brain slices have shown that bipolar neurons in the lateral septal organ responded to photostimulation comparable with mammalian ipRGC, particularly by showing depolarization and a delayed, slow response to directed light stimulation. Utilizing real-time reverse-transcription PCR, it was found that all 3 photopigments showed significantly increased gene expression in the septal-hypothalamic regions in chicks on the third day after being transferred to long-day photoperiods. Each dissected region contained structures previously proposed to have DBP. The highly significant increased gene expression for all 3 photopigments on the third, long-day photoperiod in brain regions proposed to contain 4 structures with DBP suggests that all 3 types of DBP (melanopsin, neuropsin
Deep Learning MR Imaging-based Attenuation Correction for PET/MR Imaging.
Liu, Fang; Jang, Hyungseok; Kijowski, Richard; Bradshaw, Tyler; McMillan, Alan B
2018-02-01
Purpose To develop and evaluate the feasibility of deep learning approaches for magnetic resonance (MR) imaging-based attenuation correction (AC) (termed deep MRAC) in brain positron emission tomography (PET)/MR imaging. Materials and Methods A PET/MR imaging AC pipeline was built by using a deep learning approach to generate pseudo computed tomographic (CT) scans from MR images. A deep convolutional auto-encoder network was trained to identify air, bone, and soft tissue in volumetric head MR images coregistered to CT data for training. A set of 30 retrospective three-dimensional T1-weighted head images was used to train the model, which was then evaluated in 10 patients by comparing the generated pseudo CT scan to an acquired CT scan. A prospective study was carried out for utilizing simultaneous PET/MR imaging for five subjects by using the proposed approach. Analysis of covariance and paired-sample t tests were used for statistical analysis to compare PET reconstruction error with deep MRAC and two existing MR imaging-based AC approaches with CT-based AC. Results Deep MRAC provides an accurate pseudo CT scan with a mean Dice coefficient of 0.971 ± 0.005 for air, 0.936 ± 0.011 for soft tissue, and 0.803 ± 0.021 for bone. Furthermore, deep MRAC provides good PET results, with average errors of less than 1% in most brain regions. Significantly lower PET reconstruction errors were realized with deep MRAC (-0.7% ± 1.1) compared with Dixon-based soft-tissue and air segmentation (-5.8% ± 3.1) and anatomic CT-based template registration (-4.8% ± 2.2). Conclusion The authors developed an automated approach that allows generation of discrete-valued pseudo CT scans (soft tissue, bone, and air) from a single high-spatial-resolution diagnostic-quality three-dimensional MR image and evaluated it in brain PET/MR imaging. This deep learning approach for MR imaging-based AC provided reduced PET reconstruction error relative to a CT-based standard within the brain compared
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.
Deep Logic Networks: Inserting and Extracting Knowledge From Deep Belief Networks.
Tran, Son N; d'Avila Garcez, Artur S
2018-02-01
Developments in deep learning have seen the use of layerwise unsupervised learning combined with supervised learning for fine-tuning. With this layerwise approach, a deep network can be seen as a more modular system that lends itself well to learning representations. In this paper, we investigate whether such modularity can be useful to the insertion of background knowledge into deep networks, whether it can improve learning performance when it is available, and to the extraction of knowledge from trained deep networks, and whether it can offer a better understanding of the representations learned by such networks. To this end, we use a simple symbolic language-a set of logical rules that we call confidence rules-and show that it is suitable for the representation of quantitative reasoning in deep networks. We show by knowledge extraction that confidence rules can offer a low-cost representation for layerwise networks (or restricted Boltzmann machines). We also show that layerwise extraction can produce an improvement in the accuracy of deep belief networks. Furthermore, the proposed symbolic characterization of deep networks provides a novel method for the insertion of prior knowledge and training of deep networks. With the use of this method, a deep neural-symbolic system is proposed and evaluated, with the experimental results indicating that modularity through the use of confidence rules and knowledge insertion can be beneficial to network performance.
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.
Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs.
Liu, C C; Chien, J H; Kim, J H; Chuang, Y F; Cheng, D T; Anderson, W S; Lenz, F A
2015-09-10
Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0-10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40-70 Hz) and high-gamma (HG, 70-110 Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4-7 Hz) and alpha (8-1 2 Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Targeting of deep-brain structures in nonhuman primates using MR and CT Images
NASA Astrophysics Data System (ADS)
Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.
2015-03-01
In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.
Deep brain stimulation macroelectrodes compared to multiple microelectrodes in rat hippocampus
Arcot Desai, Sharanya; Gutekunst, Claire-Anne; Potter, Steve M.; Gross, Robert E.
2014-01-01
Microelectrode arrays (wire diameter <50 μm) were compared to traditional macroelectrodes for deep brain stimulation (DBS). Understanding the neuronal activation volume may help solve some of the mysteries associated with DBS, e.g., its mechanisms of action. We used c-fos immunohistochemistry to investigate neuronal activation in the rat hippocampus caused by multi-micro- and macroelectrode stimulation. At ± 1V stimulation at 25 Hz, microelectrodes (33 μm diameter) had a radius of activation of 100 μm, which is 50% of that seen with 150 μm diameter macroelectrode stimulation. Macroelectrodes activated about 5.8 times more neurons than a single microelectrode, but displaced ~20 times more neural tissue. The sphere of influence of stimulating electrodes can be significantly increased by reducing their impedance. By ultrasonic electroplating (sonicoplating) the microelectrodes with platinum to increase their surface area and reduce their impedance by an order of magnitude, the radius of activation increased by 50 μm and more than twice the number of neurons were activated within this increased radius compared to unplated microelectrodes. We suggest that a new approach to DBS, one that uses multiple high-surface area microelectrodes, may be more therapeutically effective due to increased neuronal activation. PMID:24971060
Role of deep brain stimulation in modulating memory formation and recall
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
Towards deep learning with segregated dendrites.
Guerguiev, Jordan; Lillicrap, Timothy P; Richards, Blake A
2017-12-05
Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the neocortex optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network learns to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful higher-order representations-the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the morphology of neocortical pyramidal neurons.
NASA Astrophysics Data System (ADS)
Kim, Sungho
2017-06-01
Automatic target recognition (ATR) is a traditionally challenging problem in military applications because of the wide range of infrared (IR) image variations and the limited number of training images. IR variations are caused by various three-dimensional target poses, noncooperative weather conditions (fog and rain), and difficult target acquisition environments. Recently, deep convolutional neural network-based approaches for RGB images (RGB-CNN) showed breakthrough performance in computer vision problems, such as object detection and classification. The direct use of RGB-CNN to the IR ATR problem fails to work because of the IR database problems (limited database size and IR image variations). An IR variation-reduced deep CNN (IVR-CNN) to cope with the problems is presented. The problem of limited IR database size is solved by a commercial thermal simulator (OKTAL-SE). The second problem of IR variations is mitigated by the proposed shifted ramp function-based intensity transformation. This can suppress the background and enhance the target contrast simultaneously. The experimental results on the synthesized IR images generated by the thermal simulator (OKTAL-SE) validated the feasibility of IVR-CNN for military ATR applications.
Identification of autism spectrum disorder using deep learning and the ABIDE dataset.
Heinsfeld, Anibal Sólon; Franco, Alexandre Rosa; Craddock, R Cameron; Buchweitz, Augusto; Meneguzzi, Felipe
2018-01-01
The goal of the present study was to apply deep learning algorithms to identify autism spectrum disorder (ASD) patients from large brain imaging dataset, based solely on the patients brain activation patterns. We investigated ASD patients brain imaging data from a world-wide multi-site database known as ABIDE (Autism Brain Imaging Data Exchange). ASD is a brain-based disorder characterized by social deficits and repetitive behaviors. According to recent Centers for Disease Control data, ASD affects one in 68 children in the United States. We investigated patterns of functional connectivity that objectively identify ASD participants from functional brain imaging data, and attempted to unveil the neural patterns that emerged from the classification. The results improved the state-of-the-art by achieving 70% accuracy in identification of ASD versus control patients in the dataset. The patterns that emerged from the classification show an anticorrelation of brain function between anterior and posterior areas of the brain; the anticorrelation corroborates current empirical evidence of anterior-posterior disruption in brain connectivity in ASD. We present the results and identify the areas of the brain that contributed most to differentiating ASD from typically developing controls as per our deep learning model.
Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I
2018-01-01
Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information. PMID:29513219
Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I
2018-03-07
Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.
Camalier, Corrie R; Wang, Alice Y; McIntosh, Lindsey G; Park, Sohee; Neimat, Joseph S
2017-03-01
Computational and theoretical accounts hypothesize the basal ganglia play a supramodal "gating" role in the maintenance of working memory representations, especially in preservation from distractor interference. There are currently two major limitations to this account. The first is that supporting experiments have focused exclusively on the visuospatial domain, leaving questions as to whether such "gating" is domain-specific. The second is that current evidence relies on correlational measures, as it is extremely difficult to causally and reversibly manipulate subcortical structures in humans. To address these shortcomings, we examined non-spatial, auditory working memory performance during reversible modulation of the basal ganglia, an approach afforded by deep brain stimulation of the subthalamic nucleus. We found that subthalamic nucleus stimulation impaired auditory working memory performance, specifically in the group tested in the presence of distractors, even though the distractors were predictable and completely irrelevant to the encoding of the task stimuli. This study provides key causal evidence that the basal ganglia act as a supramodal filter in working memory processes, further adding to our growing understanding of their role in cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.
PyDBS: an automated image processing workflow for deep brain stimulation surgery.
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.
Beste, Christian; Mückschel, Moritz; Elben, Saskia; J Hartmann, Christian; McIntyre, Cameron C; Saft, Carsten; Vesper, Jan; Schnitzler, Alfons; Wojtecki, Lars
2015-07-01
Deep brain stimulation of the dorsal pallidum (globus pallidus, GP) is increasingly considered as a surgical therapeutic option in Huntington's disease (HD), but there is need to identify outcome measures useful for clinical trials. Computational models consider the GP to be part of a basal ganglia network involved in cognitive processes related to the control of actions. We examined behavioural and event-related potential (ERP) correlates of action control (i.e., error monitoring) and evaluated the effects of deep brain stimulation (DBS). We did this using a standard flanker paradigm and evaluated error-related ERPs. Patients were recruited from a prospective pilot trial for pallidal DBS in HD (trial number NCT00902889). From the initial four patients with Huntington's chorea, two patients with chronic external dorsal pallidum stimulation were available for follow-up and able to perform the task. The results suggest that the external GP constitutes an important basal ganglia element not only for error processing and behavioural adaptation but for general response monitoring processes as well. Response monitoring functions were fully controllable by switching pallidal DBS stimulation on and off. When stimulation was switched off, no neurophysiological and behavioural signs of error and general performance monitoring, as reflected by the error-related negativity and post-error slowing in reaction times were evident. The modulation of response monitoring processes by GP-DBS reflects a side effect of efforts to alleviate motor symptoms in HD. From a clinical neurological perspective, the results suggest that DBS in the external GP segment can be regarded as a potentially beneficial treatment with respect to cognitive functions.
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.
Tamir, Idit; Marmor-Levin, Odeya; Eitan, Renana; Bergman, Hagai; Israel, Zvi
2017-10-01
The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome. Copyright © 2017 Elsevier Inc. All rights reserved.
Dolz, Jose; Betrouni, Nacim; Quidet, Mathilde; Kharroubi, Dris; Leroy, Henri A; Reyns, Nicolas; Massoptier, Laurent; Vermandel, Maximilien
2016-09-01
Delineation of organs at risk (OARs) is a crucial step in surgical and treatment planning in brain cancer, where precise OARs volume delineation is required. However, this task is still often manually performed, which is time-consuming and prone to observer variability. To tackle these issues a deep learning approach based on stacking denoising auto-encoders has been proposed to segment the brainstem on magnetic resonance images in brain cancer context. Additionally to classical features used in machine learning to segment brain structures, two new features are suggested. Four experts participated in this study by segmenting the brainstem on 9 patients who underwent radiosurgery. Analysis of variance on shape and volume similarity metrics indicated that there were significant differences (p<0.05) between the groups of manual annotations and automatic segmentations. Experimental evaluation also showed an overlapping higher than 90% with respect to the ground truth. These results are comparable, and often higher, to those of the state of the art segmentation methods but with a considerably reduction of the segmentation time. Copyright © 2016 Elsevier Ltd. All rights reserved.
Modulation of human time processing by subthalamic deep brain stimulation.
Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons
2011-01-01
Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.
Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation
Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons
2011-01-01
Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767
Evaluation of high-perimeter electrode designs for deep brain stimulation
NASA Astrophysics Data System (ADS)
Howell, Bryan; Grill, Warren M.
2014-08-01
Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, complications including infections and mis-programing following surgical replacement of the battery-powered implantable pulse generator adversely impact the safety profile of this therapy. We sought to decrease power consumption and extend battery life by modifying the electrode geometry to increase stimulation efficiency. The specific goal of this study was to determine whether electrode contact perimeter or area had a greater effect on increasing stimulation efficiency. Approach. Finite-element method (FEM) models of eight prototype electrode designs were used to calculate the electrode access resistance, and the FEM models were coupled with cable models of passing axons to quantify stimulation efficiency. We also measured in vitro the electrical properties of the prototype electrode designs and measured in vivo the stimulation efficiency following acute implantation in anesthetized cats. Main results. Area had a greater effect than perimeter on altering the electrode access resistance; electrode (access or dynamic) resistance alone did not predict stimulation efficiency because efficiency was dependent on the shape of the potential distribution in the tissue; and, quantitative assessment of stimulation efficiency required consideration of the effects of the electrode-tissue interface impedance. Significance. These results advance understanding of the features of electrode geometry that are important for designing the next generation of efficient DBS electrodes.
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
Moliz, Nicolás; Katati, Majed J; Iañez, Benjamín; García, Asunción; Yagui, Eskandar; Horcajadas, Ángel
2015-01-01
Twiddler's syndrome is a rare complication associated with implantable electrical stimulation devices. First described in a patient with a pacemaker, it is a known complication in the field of cardiology. However, it is not so recognised in the world of neurosurgery, in which it has been described in relation to deep brain stimulation (DBS) devices. Characterised by manipulating either consciously or unconsciously the generator of such devices, which causes it to rotate on itself, the syndrome causes the coiling of the wiring of these systems and can lead to their rupture or the displacement of intracranial electrodes. We describe a case of twiddler's syndrome in a patient treated with DBS for obsessive-compulsive disorder, in which clinical deterioration presented after a good initial response. Control radiographs revealed rotation of the wiring system and displacement of the intracranial electrodes. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.
Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia syndrome.
Weiss, Daniel; Mielke, Carina; Wächter, Tobias; Bender, Benjamin; Liscic, Rajka M; Scholten, Marlieke; Naros, Georgios; Plewnia, Christian; Gharabaghi, Alireza; Krüger, Rejko
2015-03-01
Fragile X-associated tremor/ataxia syndrome (FXTAS) presents as complex movement disorder including tremor and cerebellar ataxia. The efficacy and safety of deep brain stimulation of the nucleus ventralis intermedius of the thalamus in atypical tremor syndromes like FXTAS remains to be determined. Here, we report the long-term outcome of three male genetically confirmed FXTAS patients treated with bilateral neurostimulation of the nucleus ventralis intermedius for up to four years. All patients demonstrated sustained improvement of both tremor and ataxia - the latter included improvement of intention tremor and axial tremor. Kinematic gait analyses further demonstrated a regularization of the gait cycle. Initial improvements of hand functional disability were not sustained and reached the preoperative level of impairment within one to two years from surgery. Our data on patients with a genetic cause of tremor show favorable outcome and may contribute to improved patient stratification for neurostimulation therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.
Messina, Giuseppe; Rizzi, Michele; Cordella, Roberto; Caraceni, Augusto; Zecca, Ernesto; Bussone, Gennaro; Franzini, Angelo; Leone, Massimo
2013-01-01
Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) has been reported as an effective treatment for primary, drug-refractory and chronic cluster headache (CCH). We here describe the use of such a procedure for the treatment of secondary CCH due to a neoplasm affecting the soft tissues of the right hemiface. A 27-year-old man affected by infiltrating angiomyolipoma of the right hemiface who subsequently developed drug refractory homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta. After surgery, the patient presented a significant reduction in frequency of pain bouts. However, because of a subsequent infection, the entire system was removed. After re-implantation of the system, successful outcome was observed at 2 years follow-up. This brief report shows the feasibility of pHyp DBS in secondary drug-refractory CCH syndromes; future reports are needed in order to confirm our positive result.
A tripolar current-steering stimulator ASIC for field shaping in deep brain stimulation.
Valente, Virgilio; Demosthenous, Andreas; Bayford, Richard
2012-06-01
A significant problem with clinical deep brain stimulation (DBS) is the high variability of its efficacy and the frequency of side effects, related to the spreading of current beyond the anatomical target area. This is the result of the lack of control that current DBS systems offer on the shaping of the electric potential distribution around the electrode. This paper presents a stimulator ASIC with a tripolar current-steering output stage, aiming at achieving more selectivity and field shaping than current DBS systems. The ASIC was fabricated in a 0.35-μ m CMOS technology occupying a core area of 0.71 mm(2). It consists of three current sourcing/sinking channels. It is capable of generating square and exponential-decay biphasic current pulses with five different time constants up to 28 ms and delivering up to 1.85 mA of cathodic current, in steps of 4 μA, from a 12 V power supply. Field shaping was validated by mapping the potential distribution when injecting current pulses through a multicontact DBS electrode in saline.
Kouzani, Abbas Z.; Tye, Susannah J.; Abulseoud, Osama A.; Amiet, Andrew; Galehdar, Amir; Kaynak, Akif; Berk, Michael
2014-01-01
Design of a rectangular spiral planar inverted-F antenna (PIFA) at 915 MHz for wireless power transmission applications is proposed. The antenna and rectifying circuitry form a rectenna, which can produce dc power from a distant radio frequency energy transmitter. The generated dc power is used to operate a low-power deep brain stimulation pulse generator. The proposed antenna has the dimensions of 10 mm \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\times\\,$ \\end{document}12.5 mm \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\times\\,$ \\end{document}1.5 mm and resonance frequency of 915 MHz with a measured bandwidth of 15 MHz at return loss of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${-}{\\rm 10}~{\\rm dB}$ \\end{document}. A dielectric substrate of FR-4 of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\varepsilon _{r}=4.8$ \\end{document} and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\delta=0.015$ \\end{document} with thickness of 1.5 mm is used for both antenna and rectifier
Boccard, Sandra G J; Rebelo, Pedro; Cheeran, Binith; Green, Alexander; FitzGerald, James J; Aziz, Tipu Z
2016-12-01
Deep brain stimulation (DBS) is a well-established treatment to reduce tremor, notably in Parkinson disease. DBS may also be effective in post-traumatic tremor, one of the most common movement disorders caused by head injury. However, the cohorts of patients often have multiple lesions that may impact the outcome depending on which fiber tracts are affected. A 20-year-old man presented after road traffic accident with severe closed head injury and polytrauma. Computed tomography scan showed left frontal and basal ganglia hemorrhagic contusions and intraventricular hemorrhage. A disabling tremor evolved in step with motor recovery. Despite high-intensity signals in the intended thalamic target, a visual analysis of the preoperative diffusion tensor imaging revealed preservation of connectivity of the intended target, ventralis oralis posterior thalamic nucleus (VOP). This was confirmed by the postoperative tractography study presented here. DBS of the VOP/zona incerta was performed. Six months postimplant, marked improvement of action (postural, kinetic, and intention) tremor was achieved. We demonstrated a strong connectivity between the VOP and the superior frontal gyrus containing the premotor cortex and other central brain areas responsible for movement control. In spite of an existing lesion in the target, the preservation of these tracts may be relevant to the improvement of the patient's symptoms by DBS. Copyright © 2016 Elsevier Inc. All rights reserved.
Flores Alves Dos Santos, Joao; Tezenas du Montcel, Sophie; Gargiulo, Marcella; Behar, Cecile; Montel, Sébastien; Hergueta, Thierry; Navarro, Soledad; Belaid, Hayat; Cloitre, Pauline; Karachi, Carine; Mallet, Luc
2017-01-01
Background Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for the motor and non-motor signs of Parkinson’s disease (PD), however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption. Methods Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS) scores from patients and carers that received the psychoeducation programme (n = 9) were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10). Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers’ anxiety and burden were also analysed. Results Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058). At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015). At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively). No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability. Conclusions Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies. PMID:28399152
Theory of feedback controlled brain stimulations for Parkinson's disease
NASA Astrophysics Data System (ADS)
Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.
2016-01-01
Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.
deepTools: a flexible platform for exploring deep-sequencing data.
Ramírez, Fidel; Dündar, Friederike; Diehl, Sarah; Grüning, Björn A; Manke, Thomas
2014-07-01
We present a Galaxy based web server for processing and visualizing deeply sequenced data. The web server's core functionality consists of a suite of newly developed tools, called deepTools, that enable users with little bioinformatic background to explore the results of their sequencing experiments in a standardized setting. Users can upload pre-processed files with continuous data in standard formats and generate heatmaps and summary plots in a straight-forward, yet highly customizable manner. In addition, we offer several tools for the analysis of files containing aligned reads and enable efficient and reproducible generation of normalized coverage files. As a modular and open-source platform, deepTools can easily be expanded and customized to future demands and developments. The deepTools webserver is freely available at http://deeptools.ie-freiburg.mpg.de and is accompanied by extensive documentation and tutorials aimed at conveying the principles of deep-sequencing data analysis. The web server can be used without registration. deepTools can be installed locally either stand-alone or as part of Galaxy. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Towards deep learning with segregated dendrites
Guerguiev, Jordan; Lillicrap, Timothy P
2017-01-01
Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the neocortex optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network learns to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful higher-order representations—the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the morphology of neocortical pyramidal neurons. PMID:29205151
In vivo three-photon imaging of deep cerebellum
NASA Astrophysics Data System (ADS)
Wang, Mengran; Wang, Tianyu; Wu, Chunyan; Li, Bo; Ouzounov, Dimitre G.; Sinefeld, David; Guru, Akash; Nam, Hyung-Song; Capecchi, Mario R.; Warden, Melissa R.; Xu, Chris
2018-02-01
We demonstrate three-photon microscopy (3PM) of mouse cerebellum at 1 mm depth by imaging both blood vessels and neurons. We compared 3PM and 2PM in the mouse cerebellum for imaging green (using excitation sources at 1300 nm and 920 nm, respectively) and red fluorescence (using excitation sources at 1680 nm and 1064 nm, respectively). 3PM enabled deeper imaging than 2PM because the use of longer excitation wavelength reduces the scattering in biological tissue and the higher order nonlinear excitation provides better 3D localization. To illustrate these two advantages quantitatively, we measured the signal decay as well as the signal-to-background ratio (SBR) as a function of depth. We performed 2-photon imaging from the brain surface all the way down to the area where the SBR reaches 1, while at the same depth, 3PM still has SBR above 30. The segmented decay curve shows that the mouse cerebellum has different effective attenuation lengths at different depths, indicating heterogeneous tissue property for this brain region. We compared the third harmonic generation (THG) signal, which is used to visualize myelinated fibers, with the decay curve. We found that the regions with shorter effective attenuation lengths correspond to the regions with more fibers. Our results indicate that the widespread, non-uniformly distributed myelinated fibers adds heterogeneity to mouse cerebellum, which poses additional challenges in deep imaging of this brain region.
Richieri, Raphaëlle; Blackman, Graham; Musil, Richard; Spatola, Giorgio; Cavanna, Andrea E; Lançon, Christophe; Régis, Jean
2018-04-26
We report the first case of a patient with severe, intractable Tourette Syndrome with comorbid Obsessive Compulsive disorder, who recovered from both disorders with gamma-knife (GK) stereotactic radiosurgery following deep brain stimulation (DBS). This case highlights the possible role of the internal capsule within the neural circuitries underlying both TS and OCD, and suggests that in cases of treatment-refractory TS and comorbid OCD, bilateral anterior capsulotomy using stereotactic radiosurgery may be a viable treatment option. Copyright © 2018 Elsevier B.V. All rights reserved.
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.
Deep Brain Stimulation for Early Stage Parkinson's Disease: An Illustrative Case
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
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.
Deep learning with convolutional neural networks for EEG decoding and visualization.
Schirrmeister, Robin Tibor; Springenberg, Jost Tobias; Fiederer, Lukas Dominique Josef; Glasstetter, Martin; Eggensperger, Katharina; Tangermann, Michael; Hutter, Frank; Burgard, Wolfram; Ball, Tonio
2017-11-01
Deep learning with convolutional neural networks (deep ConvNets) has revolutionized computer vision through end-to-end learning, that is, learning from the raw data. There is increasing interest in using deep ConvNets for end-to-end EEG analysis, but a better understanding of how to design and train ConvNets for end-to-end EEG decoding and how to visualize the informative EEG features the ConvNets learn is still needed. Here, we studied deep ConvNets with a range of different architectures, designed for decoding imagined or executed tasks from raw EEG. Our results show that recent advances from the machine learning field, including batch normalization and exponential linear units, together with a cropped training strategy, boosted the deep ConvNets decoding performance, reaching at least as good performance as the widely used filter bank common spatial patterns (FBCSP) algorithm (mean decoding accuracies 82.1% FBCSP, 84.0% deep ConvNets). While FBCSP is designed to use spectral power modulations, the features used by ConvNets are not fixed a priori. Our novel methods for visualizing the learned features demonstrated that ConvNets indeed learned to use spectral power modulations in the alpha, beta, and high gamma frequencies, and proved useful for spatially mapping the learned features by revealing the topography of the causal contributions of features in different frequency bands to the decoding decision. Our study thus shows how to design and train ConvNets to decode task-related information from the raw EEG without handcrafted features and highlights the potential of deep ConvNets combined with advanced visualization techniques for EEG-based brain mapping. Hum Brain Mapp 38:5391-5420, 2017. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.
2013-03-01
Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.
Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes
NASA Astrophysics Data System (ADS)
Howell, Bryan; Huynh, Brian; Grill, Warren M.
2015-08-01
Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS. Approach. We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo. Main results. Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45-84% less power. Similar gains in selectivity were evident with the optimized electrodes: 50% of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44 to 48% with the standard electrode to 0-14% with bipolar designs; 50% of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53 to 55% with the standard electrode to 1-5% with an array of cathodes; and, 50% of TAs could be activated while reducing activation of AOPs from 43 to 100% with the standard electrode to 2-15% with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation. Significance. Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes.
Cost-Effectiveness of Deep Brain Stimulation for Advanced Parkinson's Disease in the United States.
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.
Deep Sleep and Parietal Cortex Gene Expression Changes Are Related to Cognitive Deficits with Age
Buechel, Heather M.; Popovic, Jelena; Searcy, James L.; Porter, Nada M.; Thibault, Olivier; Blalock, Eric M.
2011-01-01
Background Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging. Methodology We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken. Principal Findings Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the active period was most strongly correlated to maze performance. Transcriptional profiles were strongly associated with behavior and age, and were validated against prior studies. Bioinformatic analysis revealed increased translation and decreased myelin/neuronal pathways. Conclusions The F344 rat appears to serve as a reasonable model for some common sleep architecture and cognitive changes seen with age in humans, including the cognitively disrupting influence of active period deep sleep. Microarray analysis suggests that the processes engaged by this sleep are consistent with its function. Thus, active period deep sleep appears temporally misaligned but mechanistically intact, leading to the following: first, aged brain tissue appears capable of generating the slow waves necessary for deep sleep, albeit at a weaker intensity than in young. Second, this activity, presented during the active period, seems disruptive rather than beneficial to cognition. Third, this active period deep sleep may be a cognitively pathologic attempt to recover age-related loss of inactive period deep sleep. Finally, therapeutic strategies aimed at reducing active period deep sleep (e.g., by promoting active period wakefulness and/or inactive period deep sleep) may
Bridges, Leslie R; Andoh, Joycelyn; Lawrence, Andrew J; Khoong, Cheryl H L; Poon, Wayne; Esiri, Margaret M; Markus, Hugh S; Hainsworth, Atticus H
2014-11-01
The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.
Perspective on the Economic Evaluation of Deep Brain Stimulation
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
Particle Swarm Optimization for Programming Deep Brain Stimulation Arrays
Peña, Edgar; Zhang, Simeng; Deyo, Steve; Xiao, YiZi; Johnson, Matthew D.
2017-01-01
Objective Deep brain stimulation (DBS) therapy relies on both precise neurosurgical targeting and systematic optimization of stimulation settings to achieve beneficial clinical outcomes. One recent advance to improve targeting is the development of DBS arrays (DBSAs) with electrodes segmented both along and around the DBS lead. However, increasing the number of independent electrodes creates the logistical challenge of optimizing stimulation parameters efficiently. Approach Solving such complex problems with multiple solutions and objectives is well known to occur in biology, in which complex collective behaviors emerge out of swarms of individual organisms engaged in learning through social interactions. Here, we developed a particle swarm optimization (PSO) algorithm to program DBSAs using a swarm of individual particles representing electrode configurations and stimulation amplitudes. Using a finite element model of motor thalamic DBS, we demonstrate how the PSO algorithm can efficiently optimize a multi-objective function that maximizes predictions of axonal activation in regions of interest (ROI, cerebellar-receiving area of motor thalamus), minimizes predictions of axonal activation in regions of avoidance (ROA, somatosensory thalamus), and minimizes power consumption. Main Results The algorithm solved the multi-objective problem by producing a Pareto front. ROI and ROA activation predictions were consistent across swarms (<1% median discrepancy in axon activation). The algorithm was able to accommodate for (1) lead displacement (1 mm) with relatively small ROI (≤9.2%) and ROA (≤1%) activation changes, irrespective of shift direction; (2) reduction in maximum per-electrode current (by 50% and 80%) with ROI activation decreasing by 5.6% and 16%, respectively; and (3) disabling electrodes (n=3 and 12) with ROI activation reduction by 1.8% and 14%, respectively. Additionally, comparison between PSO predictions and multi-compartment axon model simulations
Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.
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.
Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.
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.
Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear
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
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
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
Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L
2017-11-01
Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.
Howell, Bryan; McIntyre, Cameron C
2016-06-01
Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.
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.
NASA Astrophysics Data System (ADS)
Howell, Bryan; McIntyre, Cameron C.
2016-06-01
Objective. Deep brain stimulation (DBS) is an adjunctive therapy that is effective in treating movement disorders and shows promise for treating psychiatric disorders. Computational models of DBS have begun to be utilized as tools to optimize the therapy. Despite advancements in the anatomical accuracy of these models, there is still uncertainty as to what level of electrical complexity is adequate for modeling the electric field in the brain and the subsequent neural response to the stimulation. Approach. We used magnetic resonance images to create an image-based computational model of subthalamic DBS. The complexity of the volume conductor model was increased by incrementally including heterogeneity, anisotropy, and dielectric dispersion in the electrical properties of the brain. We quantified changes in the load of the electrode, the electric potential distribution, and stimulation thresholds of descending corticofugal (DCF) axon models. Main results. Incorporation of heterogeneity altered the electric potentials and subsequent stimulation thresholds, but to a lesser degree than incorporation of anisotropy. Additionally, the results were sensitive to the choice of method for defining anisotropy, with stimulation thresholds of DCF axons changing by as much as 190%. Typical approaches for defining anisotropy underestimate the expected load of the stimulation electrode, which led to underestimation of the extent of stimulation. More accurate predictions of the electrode load were achieved with alternative approaches for defining anisotropy. The effects of dielectric dispersion were small compared to the effects of heterogeneity and anisotropy. Significance. The results of this study help delineate the level of detail that is required to accurately model electric fields generated by DBS electrodes.
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
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.
Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease.
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.
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
ERIC Educational Resources Information Center
Baldacchino, Godfrey
2006-01-01
The "brain drain" phenomenon is typically seen as a zero-sum game, where one party's gain is presumed to be another's drain. This corresponds to deep-seated assumptions about what is "home" and what is "away". This article challenges the view, driven by much "brain drain" literature, that the dynamic is an…
Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation
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
Thalamic deep brain stimulation for tremor in Parkinson disease, essential tremor, and dystonia.
Cury, Rubens Gisbert; Fraix, Valerie; Castrioto, Anna; Pérez Fernández, Maricely Ambar; Krack, Paul; Chabardes, Stephan; Seigneuret, Eric; Alho, Eduardo Joaquim Lopes; Benabid, Alim-Louis; Moro, Elena
2017-09-26
To report on the long-term outcomes of deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) in Parkinson disease (PD), essential tremor (ET), and dystonic tremor. One hundred fifty-nine patients with PD, ET, and dystonia underwent VIM DBS due to refractory tremor at the Grenoble University Hospital. The primary outcome was a change in the tremor scores at 1 year after surgery and at the latest follow-up (21 years). Secondary outcomes included the relationship between tremor score reduction over time and the active contact position. Tremor scores (Unified Parkinson's Disease Rating Scale-III, items 20 and 21; Fahn, Tolosa, Marin Tremor Rating Scale) and the coordinates of the active contacts were recorded. Ninety-eight patients were included. Patients with PD and ET had sustained improvement in tremor with VIM stimulation (mean improvement, 70% and 66% at 1 year; 63% and 48% beyond 10 years, respectively; p < 0.05). There was no significant loss of stimulation benefit over time ( p > 0.05). Patients with dystonia exhibited a moderate response at 1-year follow-up (41% tremor improvement, p = 0.027), which was not sustained after 5 years (30% improvement, p = 0.109). The more dorsal active contacts' coordinates in the right lead were related to a better outcome 1 year after surgery ( p = 0.029). During the whole follow-up, forty-eight patients (49%) experienced minor side effects, whereas 2 (2.0%) had serious events (brain hemorrhage and infection). VIM DBS is an effective long-term (beyond 10 years) treatment for tremor in PD and ET. Effects on dystonic tremor were modest and transient. This provides Class IV evidence. It is an observational study. © 2017 American Academy of Neurology.
Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.
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.
Nagahama, Hiroshi; Suzuki, Kengo; Shonai, Takaharu; Aratani, Kazuki; Sakurai, Yuuki; Nakamura, Manami; Sakata, Motomichi
2015-01-01
Electrodes are surgically implanted into the subthalamic nucleus (STN) of Parkinson's disease patients to provide deep brain stimulation. For ensuring correct positioning, the anatomic location of the STN must be determined preoperatively. Magnetic resonance imaging has been used for pinpointing the location of the STN. To identify the optimal imaging sequence for identifying the STN, we compared images produced with T2 star-weighted angiography (SWAN), gradient echo T2*-weighted imaging, and fast spin echo T2-weighted imaging in 6 healthy volunteers. Our comparison involved measurement of the contrast-to-noise ratio (CNR) for the STN and substantia nigra and a radiologist's interpretations of the images. Of the sequences examined, the CNR and qualitative scores were significantly higher on SWAN images than on other images (p < 0.01) for STN visualization. Kappa value (0.74) on SWAN images was the highest in three sequences for visualizing the STN. SWAN is the sequence best suited for identifying the STN at the present time.
Bui, Huu Phuoc; Tomar, Satyendra; Courtecuisse, Hadrien; Audette, Michel; Cotin, Stéphane; Bordas, Stéphane P A
2018-05-01
An error-controlled mesh refinement procedure for needle insertion simulations is presented. As an example, the procedure is applied for simulations of electrode implantation for deep brain stimulation. We take into account the brain shift phenomena occurring when a craniotomy is performed. We observe that the error in the computation of the displacement and stress fields is localised around the needle tip and the needle shaft during needle insertion simulation. By suitably and adaptively refining the mesh in this region, our approach enables to control, and thus to reduce, the error whilst maintaining a coarser mesh in other parts of the domain. Through academic and practical examples we demonstrate that our adaptive approach, as compared with a uniform coarse mesh, increases the accuracy of the displacement and stress fields around the needle shaft and, while for a given accuracy, saves computational time with respect to a uniform finer mesh. This facilitates real-time simulations. The proposed methodology has direct implications in increasing the accuracy, and controlling the computational expense of the simulation of percutaneous procedures such as biopsy, brachytherapy, regional anaesthesia, or cryotherapy. Moreover, the proposed approach can be helpful in the development of robotic surgeries because the simulation taking place in the control loop of a robot needs to be accurate, and to occur in real time. Copyright © 2018 John Wiley & Sons, Ltd.
Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.
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.
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.
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.
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.
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
Owen, S L F; Heath, J; Kringelbach, M L; Stein, J F; Aziz, T Z
2007-10-01
This study aimed to find out whether preoperative diffusion tensor imaging (DTI) and probabilistic tractography could help with surgical planning for deep brain stimulation in the periaqueductal/periventricular grey area (PAG/PVG) in a patient with lower leg stump pain. A preoperative DTI was obtained from the patient, who then received DBS surgery in the PAG/PVG area with good pain relief. The postoperative MRI scan showing electrode placement was used to calculate four seed areas to represent the contacts on the Medtronic 3387 electrode. Probabilistic tractography was then performed from the pre-operative DTI image. Tracts were seen to connect to many areas within the pain network from the four different contacts. These initial findings suggest that preoperative DTI scanning and probabilistic tractography may be able to assist surgical planning in the future.
Body and brain temperature coupling: the critical role of cerebral blood flow
Ackerman, Joseph J. H.; Yablonskiy, Dmitriy A.
2010-01-01
Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; α-chloralose, αCS; and isoflurane, IF) with αCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO2 in 40% O2 and 55% N2). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under αCS anesthesia (ca. 2°C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials—αCS anesthesia resulted in the largest brain temperature increase (0.32 ± 0.08°C), while CH and IF anesthesia lead to smaller increases (0.12 ± 0.03 and 0.16 ± 0.05°C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2–3 min under CH and IF anesthesia and ~4 min under αCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures. PMID:19277681
Body and brain temperature coupling: the critical role of cerebral blood flow.
Zhu, Mingming; Ackerman, Joseph J H; Yablonskiy, Dmitriy A
2009-08-01
Direct measurements of deep-brain and body-core temperature were performed on rats to determine the influence of cerebral blood flow (CBF) on brain temperature regulation under static and dynamic conditions. Static changes of CBF were achieved using different anesthetics (chloral hydrate, CH; alpha-chloralose, alphaCS; and isoflurane, IF) with alphaCS causing larger decreases in CBF than CH and IF; dynamic changes were achieved by inducing transient hypercapnia (5% CO(2) in 40% O(2) and 55% N(2)). Initial deep-brain/body-core temperature differentials were anesthetic-type dependent with the largest differential observed with rats under alphaCS anesthesia (ca. 2 degrees C). Hypercapnia induction raised rat brain temperature under all three anesthesia regimes, but by different anesthetic-dependent amounts correlated with the initial differentials--alphaCS anesthesia resulted in the largest brain temperature increase (0.32 +/- 0.08 degrees C), while CH and IF anesthesia lead to smaller increases (0.12 +/- 0.03 and 0.16 +/- 0.05 degrees C, respectively). The characteristic temperature transition time for the hypercapnia-induced temperature increase was 2-3 min under CH and IF anesthesia and approximately 4 min under alphaCS anesthesia. We conclude that both, the deep-brain/body-core temperature differential and the characteristic temperature transition time correlate with CBF: a lower CBF promotes higher deep-brain/body-core temperature differentials and, upon hypercapnia challenge, longer characteristic transition times to increased temperatures.
NASA Astrophysics Data System (ADS)
Zavala, J. A.; Aretxaga, I.; Geach, J. E.; Hughes, D. H.; Birkinshaw, M.; Chapin, E.; Chapman, S.; Chen, Chian-Chou; Clements, D. L.; Dunlop, J. S.; Farrah, D.; Ivison, R. J.; Jenness, T.; Michałowski, M. J.; Robson, E. I.; Scott, Douglas; Simpson, J.; Spaans, M.; van der Werf, P.
2017-01-01
We present deep observations at 450 and 850 μm in the Extended Groth Strip field taken with the SCUBA-2 camera mounted on the James Clerk Maxwell Telescope as part of the deep SCUBA-2 Cosmology Legacy Survey (S2CLS), achieving a central instrumental depth of σ450 = 1.2 mJy beam-1 and σ850 = 0.2 mJy beam-1. We detect 57 sources at 450 μm and 90 at 850 μm with signal-to-noise ratio >3.5 over ˜70 arcmin2. From these detections, we derive the number counts at flux densities S450 > 4.0 mJy and S850 > 0.9 mJy, which represent the deepest number counts at these wavelengths derived using directly extracted sources from only blank-field observations with a single-dish telescope. Our measurements smoothly connect the gap between previous shallower blank-field single-dish observations and deep interferometric ALMA results. We estimate the contribution of our SCUBA-2 detected galaxies to the cosmic infrared background (CIB), as well as the contribution of 24 μm-selected galaxies through a stacking technique, which add a total of 0.26 ± 0.03 and 0.07 ± 0.01 MJy sr-1, at 450 and 850 μm, respectively. These surface brightnesses correspond to 60 ± 20 and 50 ± 20 per cent of the total CIB measurements, where the errors are dominated by those of the total CIB. Using the photometric redshifts of the 24 μm-selected sample and the redshift distributions of the submillimetre galaxies, we find that the redshift distribution of the recovered CIB is different at each wavelength, with a peak at z ˜ 1 for 450 μm and at z ˜ 2 for 850 μm, consistent with previous observations and theoretical models.
Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution.
Smaers, J B; Soligo, C
2013-05-22
Comparative analyses of primate brain evolution have highlighted changes in size and internal organization as key factors underlying species diversity. It remains, however, unclear (i) how much variation in mosaic brain reorganization versus variation in relative brain size contributes to explaining the structural neural diversity observed across species, (ii) which mosaic changes contribute most to explaining diversity, and (iii) what the temporal origin, rates and processes are that underlie evolutionary shifts in mosaic reorganization for individual branches of the primate tree of life. We address these questions by combining novel comparative methods that allow assessing the temporal origin, rate and process of evolutionary changes on individual branches of the tree of life, with newly available data on volumes of key brain structures (prefrontal cortex, frontal motor areas and cerebrocerebellum) for a sample of 17 species (including humans). We identify patterns of mosaic change in brain evolution that mirror brain systems previously identified by electrophysiological and anatomical tract-tracing studies in non-human primates and functional connectivity MRI studies in humans. Across more than 40 Myr of anthropoid primate evolution, mosaic changes contribute more to explaining neural diversity than changes in relative brain size, and different mosaic patterns are differentially selected for when brains increase or decrease in size. We identify lineage-specific evolutionary specializations for all branches of the tree of life covered by our sample and demonstrate deep evolutionary roots for mosaic patterns associated with motor control and learning.
Brain reorganization, not relative brain size, primarily characterizes anthropoid brain evolution
Smaers, J. B.; Soligo, C.
2013-01-01
Comparative analyses of primate brain evolution have highlighted changes in size and internal organization as key factors underlying species diversity. It remains, however, unclear (i) how much variation in mosaic brain reorganization versus variation in relative brain size contributes to explaining the structural neural diversity observed across species, (ii) which mosaic changes contribute most to explaining diversity, and (iii) what the temporal origin, rates and processes are that underlie evolutionary shifts in mosaic reorganization for individual branches of the primate tree of life. We address these questions by combining novel comparative methods that allow assessing the temporal origin, rate and process of evolutionary changes on individual branches of the tree of life, with newly available data on volumes of key brain structures (prefrontal cortex, frontal motor areas and cerebrocerebellum) for a sample of 17 species (including humans). We identify patterns of mosaic change in brain evolution that mirror brain systems previously identified by electrophysiological and anatomical tract-tracing studies in non-human primates and functional connectivity MRI studies in humans. Across more than 40 Myr of anthropoid primate evolution, mosaic changes contribute more to explaining neural diversity than changes in relative brain size, and different mosaic patterns are differentially selected for when brains increase or decrease in size. We identify lineage-specific evolutionary specializations for all branches of the tree of life covered by our sample and demonstrate deep evolutionary roots for mosaic patterns associated with motor control and learning. PMID:23536600
Deep Extragalactic X-Ray Surveys
NASA Astrophysics Data System (ADS)
Brandt, W. N.; Hasinger, G.
2005-09-01
Deep surveys of the cosmic X-ray background are reviewed in the context of observational progress enabled by the Chandra X-Ray Observatory and the X-Ray Multi-Mirror Mission-Newton. The sources found by deep surveys are described along with their redshift and luminosity distributions, and the effectiveness of such surveys at selecting active galactic nuclei (AGN) is assessed. Some key results from deep surveys are highlighted, including (a) measurements of AGN evolution and the growth of supermassive black holes, (b) constraints on the demography and physics of high-redshift AGN, (c) the X-ray AGN content of infrared and submillimeter galaxies, and (d) X-ray emission from distant starburst and normal galaxies. We also describe some outstanding problems and future prospects for deep extragalactic X-ray surveys.
Representational Distance Learning for Deep Neural Networks
McClure, Patrick; Kriegeskorte, Nikolaus
2016-01-01
Deep neural networks (DNNs) provide useful models of visual representational transformations. We present a method that enables a DNN (student) to learn from the internal representational spaces of a reference model (teacher), which could be another DNN or, in the future, a biological brain. Representational spaces of the student and the teacher are characterized by representational distance matrices (RDMs). We propose representational distance learning (RDL), a stochastic gradient descent method that drives the RDMs of the student to approximate the RDMs of the teacher. We demonstrate that RDL is competitive with other transfer learning techniques for two publicly available benchmark computer vision datasets (MNIST and CIFAR-100), while allowing for architectural differences between student and teacher. By pulling the student's RDMs toward those of the teacher, RDL significantly improved visual classification performance when compared to baseline networks that did not use transfer learning. In the future, RDL may enable combined supervised training of deep neural networks using task constraints (e.g., images and category labels) and constraints from brain-activity measurements, so as to build models that replicate the internal representational spaces of biological brains. PMID:28082889
Representational Distance Learning for Deep Neural Networks.
McClure, Patrick; Kriegeskorte, Nikolaus
2016-01-01
Deep neural networks (DNNs) provide useful models of visual representational transformations. We present a method that enables a DNN (student) to learn from the internal representational spaces of a reference model (teacher), which could be another DNN or, in the future, a biological brain. Representational spaces of the student and the teacher are characterized by representational distance matrices (RDMs). We propose representational distance learning (RDL), a stochastic gradient descent method that drives the RDMs of the student to approximate the RDMs of the teacher. We demonstrate that RDL is competitive with other transfer learning techniques for two publicly available benchmark computer vision datasets (MNIST and CIFAR-100), while allowing for architectural differences between student and teacher. By pulling the student's RDMs toward those of the teacher, RDL significantly improved visual classification performance when compared to baseline networks that did not use transfer learning. In the future, RDL may enable combined supervised training of deep neural networks using task constraints (e.g., images and category labels) and constraints from brain-activity measurements, so as to build models that replicate the internal representational spaces of biological brains.