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.

Systems for deep brain stimulation: review of technical features.

PubMed

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.

Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy.

PubMed

James, J H; Ziparo, V; Jeppsson, B; Fischer, J E

1979-10-13

It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.

The PennBMBI: Design of a General Purpose Wireless Brain-Machine-Brain Interface System.

PubMed

Liu, Xilin; Zhang, Milin; Subei, Basheer; Richardson, Andrew G; Lucas, Timothy H; Van der Spiegel, Jan

2015-04-01

In this paper, a general purpose wireless Brain-Machine-Brain Interface (BMBI) system is presented. The system integrates four battery-powered wireless devices for the implementation of a closed-loop sensorimotor neural interface, including a neural signal analyzer, a neural stimulator, a body-area sensor node and a graphic user interface implemented on the PC end. The neural signal analyzer features a four channel analog front-end with configurable bandpass filter, gain stage, digitization resolution, and sampling rate. The target frequency band is configurable from EEG to single unit activity. A noise floor of 4.69 μVrms is achieved over a bandwidth from 0.05 Hz to 6 kHz. Digital filtering, neural feature extraction, spike detection, sensing-stimulating modulation, and compressed sensing measurement are realized in a central processing unit integrated in the analyzer. A flash memory card is also integrated in the analyzer. A 2-channel neural stimulator with a compliance voltage up to ± 12 V is included. The stimulator is capable of delivering unipolar or bipolar, charge-balanced current pulses with programmable pulse shape, amplitude, width, pulse train frequency and latency. A multi-functional sensor node, including an accelerometer, a temperature sensor, a flexiforce sensor and a general sensor extension port has been designed. A computer interface is designed to monitor, control and configure all aforementioned devices via a wireless link, according to a custom designed communication protocol. Wireless closed-loop operation between the sensory devices, neural stimulator, and neural signal analyzer can be configured. The proposed system was designed to link two sites in the brain, bridging the brain and external hardware, as well as creating new sensory and motor pathways for clinical practice. Bench test and in vivo experiments are performed to verify the functions and performances of the system.

New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

PubMed Central

Lane, Hsien-Yuan

2017-01-01

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future. PMID:28491480

[Long-term care of Parkinson patients with deep brain stimulation].

PubMed

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.

Massage Changes Babies' Body, Brain and Behavior

NASA Astrophysics Data System (ADS)

Ishikawa, Chihiro; Shiga, Takashi

Tactile stimulation is an important factor in mother-infant interactions. Many studies on both human and animals have shown that tactile stimulation during the neonatal period has various beneficial effects in the subsequent growth of the body and brain. In particular, massage is often applied to preterm human babies as “touch care”, because tactile stimulation together with kinesthetic stimulation increases body weight, which is accompanied by behavioral development and the changes of endocrine and neural conditions. Among them, the elevation of insulin-like growth factor-1, catecholamine, and vagus nerve activity may underlie the body weight gain. Apart from the body weight gain, tactile stimulation has various effects on the nervous system and endocrine system. For example, it has been reported that tactile stimulation on human and animal babies activates parasympathetic nervous systems, while suppresses the hypothalamic-pituitary-adrenalcortical (HPA) axis, which may be related to the reduction of emotionality, anxiety-like behavior, and pain sensitivity. In addition, animal experiments have shown that tactile stimulation improves learning and memory. Facilitation of the neuronal activity and the morphological changes including the hippocampal synapse may underlie the improvement of the learning and memory. In conclusion, it has been strongly suggested that tactile stimulation in early life has beneficial effects on body, brain structure and function, which are maintained throughout life.

[Neurological and technical aspects of deep brain stimulation].

PubMed

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).

Non-invasive brain stimulation approaches to fibromyalgia pain

PubMed Central

Short, Baron; Borckardt, Jeffrey J; George, Mark; Beam, Will; Reeves, Scott T

2010-01-01

Fibromyalgia is a poorly understood disorder that likely involves central nervous system sensory hypersensitivity. There are a host of genetic, neuroendocrine and environmental abnormalities associated with the disease, and recent research findings suggest enhanced sensory processing, and abnormalities in central monoamines and cytokines expression in patients with fibromyalgia. The morbidity and financial costs associated with fibromyalgia are quite high despite conventional treatments with antidepressants, anticonvulsants, low-impact aerobic exercise and psychotherapy. Noninvasive brain stimulation techniques, such as transcranial direct current stimulation, transcranial magnetic stimulation, and electroconvulsive therapy are beginning to be studied as possible treatments for fibromyalgia pain. Early studies appear promising but more work is needed. Future directions in clinical care may include innovative combinations of noninvasive brain stimulation, pharmacological augmentation, and behavior therapies. PMID:21841959

Using non-invasive brain stimulation to augment motor training-induced plasticity

PubMed Central

Bolognini, Nadia; Pascual-Leone, Alvaro; Fregni, Felipe

2009-01-01

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date. PMID:19292910

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.

A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation.

PubMed

Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

2013-09-01

A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro .

A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation

PubMed Central

Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

2014-01-01

A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro. PMID:24678126

MRI Guided Brain Stimulation without the Use of a Neuronavigation System

PubMed Central

Vaghefi, Ehsan; Byblow, Winston D.; Stinear, Cathy M.; Thompson, Benjamin

2015-01-01

A key issue in the field of noninvasive brain stimulation (NIBS) is the accurate localization of scalp positions that correspond to targeted cortical areas. The current gold standard is to combine structural and functional brain imaging with a commercially available “neuronavigation” system. However, neuronavigation systems are not commonplace outside of specialized research environments. Here we describe a technique that allows for the use of participant-specific functional and structural MRI data to guide NIBS without a neuronavigation system. Surface mesh representations of the head were generated using Brain Voyager and vectors linking key anatomical landmarks were drawn on the mesh. Our technique was then used to calculate the precise distances on the scalp corresponding to these vectors. These calculations were verified using actual measurements of the head and the technique was used to identify a scalp position corresponding to a brain area localized using functional MRI. PMID:26413537

Activation of sensory cortex by imagined genital stimulation: an fMRI analysis.

PubMed

Wise, Nan J; Frangos, Eleni; Komisaruk, Barry R

2016-01-01

During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. This study extends our previous findings by further characterizing how the brain differentially processes physical 'touch' stimulation and 'imagined' stimulation. Eleven healthy women (age range 29-74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions - imagined dildo self-stimulation and imagined speculum stimulation - were included to characterize the effects of erotic versus non-erotic imagery. Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the 'reward system'. In addition, these results suggest a mechanism by which some individuals may be able to generate orgasm by imagery in the absence of physical stimulation.

Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

NASA Astrophysics Data System (ADS)

Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

2015-03-01

Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

Network connectivity and individual responses to brain stimulation in the human motor system.

PubMed

Cárdenas-Morales, Lizbeth; Volz, Lukas J; Michely, Jochen; Rehme, Anne K; Pool, Eva-Maria; Nettekoven, Charlotte; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2014-07-01

The mechanisms driving cortical plasticity in response to brain stimulation are still incompletely understood. We here explored whether neural activity and connectivity in the motor system relate to the magnitude of cortical plasticity induced by repetitive transcranial magnetic stimulation (rTMS). Twelve right-handed volunteers underwent functional magnetic resonance imaging during rest and while performing a simple hand motor task. Resting-state functional connectivity, task-induced activation, and task-related effective connectivity were assessed for a network of key motor areas. We then investigated the effects of intermittent theta-burst stimulation (iTBS) on motor-evoked potentials (MEP) for up to 25 min after stimulation over left primary motor cortex (M1) or parieto-occipital vertex (for control). ITBS-induced increases in MEP amplitudes correlated negatively with movement-related fMRI activity in left M1. Control iTBS had no effect on M1 excitability. Subjects with better response to M1-iTBS featured stronger preinterventional effective connectivity between left premotor areas and left M1. In contrast, resting-state connectivity did not predict iTBS aftereffects. Plasticity-related changes in M1 following brain stimulation seem to depend not only on local factors but also on interconnected brain regions. Predominantly activity-dependent properties of the cortical motor system are indicative of excitability changes following induction of cortical plasticity with rTMS. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effect of deep brain stimulation on the speech motor system.

PubMed

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.

[Abscess at the implant site following apical parodontitis. Hardware-related complications of deep brain stimulation].

PubMed

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.

Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor.

PubMed

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.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

PubMed Central

Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.

2017-01-01

The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947

The Use of Non-invasive Brain Stimulation Techniques to Facilitate Recovery from Post-stroke Aphasia

PubMed Central

Marchina, Sarah; Wan, Catherine Y.

2011-01-01

Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10–15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies. PMID:21842404

Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease.

PubMed

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.

Focal stimulation of the brain by entirely extracranial means. An example of radiation controlled focal pharmacology

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

Remler, M.P.

A method for focal stimulation of the brain by entirely extracranial means is presented. A focal x ray lesion of cortex was made that reduces the blood-brain barrier in that area. Then parenteral penicillin was administered. Penicillin is primarily confined to the vascular space by the blood-brain barrier in all parts of the brain except for some leakage into the brain at higher doses. An increased concentration of penicillin is created in the irradiated cortex. The penicillin creates a focal epileptic lesion in the irradiated area. This is an example of radiation-controlled focal pharmacology in the central nervous system. (auth)

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

PubMed

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

PubMed Central

Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

2015-01-01

Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease. PMID:25653107

Abnormal brain structure implicated in stimulant drug addiction.

PubMed

Ersche, Karen D; Jones, P Simon; Williams, Guy B; Turton, Abigail J; Robbins, Trevor W; Bullmore, Edward T

2012-02-03

Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

PubMed

Bassi, Gabriel Shimizu; Dias, Daniel Penteado Martins; Franchin, Marcelo; Talbot, Jhimmy; Reis, Daniel Gustavo; Menezes, Gustavo Batista; Castania, Jaci Airton; Garcia-Cairasco, Norberto; Resstel, Leonardo Barbosa Moraes; Salgado, Helio Cesar; Cunha, Fernando Queiróz; Cunha, Thiago Mattar; Ulloa, Luis; Kanashiro, Alexandre

2017-08-01

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment and modulation of neuroplasticity in rehabilitation with transcranial magnetic stimulation

PubMed Central

Bashir, Shahid; Mizrahi, Ilan; Weaver, Kayleen; Fregni, Felipe; Pascual-Leone, Alvaro

2013-01-01

Despite intensive efforts towards the improvement of outcomes after acquired brain injury functional recovery is often limited. One reasons is the challenge in assessing and guiding plasticity after brain injury. In this context, Transcranial Magnetic Stimulation (TMS) - a noninvasive tool of brain stimulation - could play a major role. TMS has shown to be a reliable tool to measure plastic changes in the motor cortex associated with interventions in the motor system; such as motor training and motor cortex stimulation. In addition, as illustrated by the experience in promoting recovery from stroke, TMS a promising therapeutic tool to minimize motor, speech, cognitive, and mood deficits. In this review, we will focus on stroke to discuss how TMS can provide insights into the mechanisms of neurological recovery, and can be used for measurement and modulation of plasticity after an acquired brain insult. PMID:21172687

A brain-spine interface alleviating gait deficits after spinal cord injury in primates.

PubMed

Capogrosso, Marco; Milekovic, Tomislav; Borton, David; Wagner, Fabien; Moraud, Eduardo Martin; Mignardot, Jean-Baptiste; Buse, Nicolas; Gandar, Jerome; Barraud, Quentin; Xing, David; Rey, Elodie; Duis, Simone; Jianzhong, Yang; Ko, Wai Kin D; Li, Qin; Detemple, Peter; Denison, Tim; Micera, Silvestro; Bezard, Erwan; Bloch, Jocelyne; Courtine, Grégoire

2016-11-10

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

Recruitment of Additional Corticospinal Pathways in the Human Brain with State-Dependent Paired Associative Stimulation.

PubMed

Kraus, Dominic; Naros, Georgios; Guggenberger, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

2018-02-07

Standard brain stimulation protocols modify human motor cortex excitability by modulating the gain of the activated corticospinal pathways. However, the restoration of motor function following lesions of the corticospinal tract requires also the recruitment of additional neurons to increase the net corticospinal output. For this purpose, we investigated a novel protocol based on brain state-dependent paired associative stimulation.Motor imagery (MI)-related electroencephalography was recorded in healthy males and females for brain state-dependent control of both cortical and peripheral stimulation in a brain-machine interface environment. State-dependency was investigated with concurrent, delayed, and independent stimulation relative to the MI task. Specifically, sensorimotor event-related desynchronization (ERD) in the β-band (16-22 Hz) triggered peripheral stimulation through passive hand opening by a robotic orthosis and transcranial magnetic stimulation to the respective cortical motor representation, either synchronously or subsequently. These MI-related paradigms were compared with paired cortical and peripheral input applied independent of the brain state. Cortical stimulation resulted in a significant increase in corticospinal excitability only when applied brain state-dependently and synchronously to peripheral input. These gains were resistant to a depotentiation task, revealed a nonlinear evolution of plasticity, and were mediated via the recruitment of additional corticospinal neurons rather than via synchronization of neuronal firing. Recruitment of additional corticospinal pathways may be achieved when cortical and peripheral inputs are applied concurrently, and during β-ERD. These findings resemble a gating mechanism and are potentially important for developing closed-loop brain stimulation for the treatment of hand paralysis following lesions of the corticospinal tract. SIGNIFICANCE STATEMENT The activity state of the motor system influences the excitability of corticospinal pathways to external input. State-dependent interventions harness this property to increase the connectivity between motor cortex and muscles. These stimulation protocols modulate the gain of the activated pathways, but not the overall corticospinal recruitment. In this study, a brain-machine interface paired peripheral stimulation through passive hand opening with transcranial magnetic stimulation to the respective cortical motor representation during volitional β-band desynchronization. Cortical stimulation resulted in the recruitment of additional corticospinal pathways, but only when applied brain state-dependently and synchronously to peripheral input. These effects resemble a gating mechanism and may be important for the restoration of motor function following lesions of the corticospinal tract. Copyright © 2018 the authors 0270-6474/18/381397-12$15.00/0.

Control of Abnormal Synchronization in Neurological Disorders

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2014-01-01

In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

Brain Stimulation in Addiction

PubMed Central

Salling, Michael C; Martinez, Diana

2016-01-01

Localized stimulation of the human brain to treat neuropsychiatric disorders has been in place for over 20 years. Although these methods have been used to a greater extent for mood and movement disorders, recent work has explored brain stimulation methods as potential treatments for addiction. The rationale behind stimulation therapy in addiction involves reestablishing normal brain function in target regions in an effort to dampen addictive behaviors. In this review, we present the rationale and studies investigating brain stimulation in addiction, including transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Overall, these studies indicate that brain stimulation has an acute effect on craving for drugs and alcohol, but few studies have investigated the effect of brain stimulation on actual drug and alcohol use or relapse. Stimulation therapies may achieve their effect through direct or indirect modulation of brain regions involved in addiction, either acutely or through plastic changes in neuronal transmission. Although these mechanisms are not well understood, further identification of the underlying neurobiology of addiction and rigorous evaluation of brain stimulation methods has the potential for unlocking an effective, long-term treatment of addiction. PMID:27240657

Driving working memory with frequency-tuned noninvasive brain stimulation.

PubMed

Albouy, Philippe; Baillet, Sylvain; Zatorre, Robert J

2018-04-29

Frequency-tuned noninvasive brain stimulation is a recent approach in cognitive neuroscience that involves matching the frequency of transcranially applied electromagnetic fields to that of specific oscillatory components of the underlying neurophysiology. The objective of this method is to modulate ongoing/intrinsic brain oscillations, which correspond to rhythmic fluctuations of neural excitability, to causally change behavior. We review the impact of frequency-tuned noninvasive brain stimulation on the research field of human working memory. We argue that this is a powerful method to probe and understand the mechanisms of memory functions, targeting specifically task-related oscillatory dynamics, neuronal representations, and brain networks. We report the main behavioral and neurophysiological outcomes published to date, in particular, how functionally relevant oscillatory signatures in signal power and interregional connectivity yield causal changes of working memory abilities. We also present recent developments of the technique that aim to modulate cross-frequency coupling in polyrhythmic neural activity. Overall, the method has led to significant advances in our understanding of the mechanisms of systems neuroscience, and the role of brain oscillations in cognition and behavior. We also emphasize the translational impact of noninvasive brain stimulation techniques in the development of therapeutic approaches. © 2018 New York Academy of Sciences.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

EKG-based detection of deep brain stimulation in fMRI studies.

PubMed

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.

Advances in the Neuroscience of Intelligence: from Brain Connectivity to Brain Perturbation.

PubMed

Santarnecchi, Emiliano; Rossi, Simone

2016-12-06

Our view is that intelligence, as expression of the complexity of the human brain and of its evolutionary path, represents an intriguing example of "system level brain plasticity": tangible proofs of this assertion lie in the strong links intelligence has with vital brain capacities as information processing (i.e., pure, rough capacity to transfer information in an efficient way), resilience (i.e., the ability to cope with loss of efficiency and/or loss of physical elements in a network) and adaptability (i.e., being able to efficiently rearrange its dynamics in response to environmental demands). Current evidence supporting this view move from theoretical models correlating intelligence and individual response to systematic "lesions" of brain connectivity, as well as from the field of Noninvasive Brain Stimulation (NiBS). Perturbation-based approaches based on techniques as transcranial magnetic stimulation (TMS) and transcranial alternating current stimulation (tACS), are opening new in vivo scenarios which could allow to disclose more causal relationship between intelligence and brain plasticity, overcoming the limitations of brain-behavior correlational evidence.

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

PubMed Central

Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2013-01-01

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound. PMID:24038075

Vagus nerve stimulation for the treatment of depression and other neuropsychiatric disorders.

PubMed

George, Mark S; Nahas, Ziad; Borckardt, Jeffrey J; Anderson, Berry; Burns, Carol; Kose, Samet; Short, E Baron

2007-01-01

Vagus nerve stimulation is an interesting new approach to treating neuropsychiatric diseases within the class of brain-stimulation devices sometimes labeled 'neuromodulators'. With vagus nerve stimulation, a battery-powered generator implanted in the chest wall connects to a wire wrapped around the vagus nerve in the neck, and sends intermittent pulses of electricity along the nerve directly into the brain. This mechanism takes advantage of the natural role of the vagus nerve in conveying information into the brain concerning homeostatic information (e.g., hunger, chest pain and respirations). Vagus nerve stimulation therapy is US FDA approved for the adjunctive treatment of epilepsy and has recently been FDA approved for the treatment of medication-resistant depression. Owing to its novel route into the brain, it has no drug-drug interactions or systemic side effects. This treatment also appears to have high long-term tolerability in patients, with low rates of patients relapsing on vagus nerve stimulation or becoming tolerant. However, alongside the excitement and enthusiasm for this new treatment, a lack of Class I evidence of efficacy in treating depression is currently slowing down adoption by psychiatrists. Much more research is needed regarding exactly how to refine and deliver the electrical pulses and how this differentially affects brain function in health and disease.

Design of optimal nonlinear network controllers for Alzheimer's disease.

PubMed

Sanchez-Rodriguez, Lazaro M; Iturria-Medina, Yasser; Baines, Erica A; Mallo, Sabela C; Dousty, Mehdy; Sotero, Roberto C

2018-05-01

Brain stimulation can modulate the activity of neural circuits impaired by Alzheimer's disease (AD), having promising clinical benefit. However, all individuals with the same condition currently receive identical brain stimulation, with limited theoretical basis for this generic approach. In this study, we introduce a control theory framework for obtaining exogenous signals that revert pathological electroencephalographic activity in AD at a minimal energetic cost, while reflecting patients' biological variability. We used anatomical networks obtained from diffusion magnetic resonance images acquired by the Alzheimer's Disease Neuroimaging Initiative (ADNI) as mediators for the interaction between Duffing oscillators. The nonlinear nature of the brain dynamics is preserved, given that we extend the so-called state-dependent Riccati equation control to reflect the stimulation objective in the high-dimensional neural system. By considering nonlinearities in our model, we identified regions for which control inputs fail to correct abnormal activity. There are changes to the way stimulated regions are ranked in terms of the energetic cost of controlling the entire network, from a linear to a nonlinear approach. We also found that limbic system and basal ganglia structures constitute the top target locations for stimulation in AD. Patients with highly integrated anatomical networks-namely, networks having low average shortest path length, high global efficiency-are the most suitable candidates for the propagation of stimuli and consequent success on the control task. Other diseases associated with alterations in brain dynamics and the self-control mechanisms of the brain can be addressed through our framework.

Effect of electrical stimulation therapy on upper extremity functional recovery and cerebral cortical changes in patients with chronic hemiplegia.

PubMed

Sasaki, Kana; Matsunaga, Toshiki; Tomite, Takenori; Yoshikawa, Takayuki; Shimada, Yoichi

2012-04-01

Hemiplegia is a common sequel of stroke and assisted living care is needed in many cases. The purpose of this study was to evaluate the effect of using surface electrode stimulation device in rehabilitation, in terms of functional improvement in upper limb and the changes in brain activation related to central nervous system reconstruction. Five patients with chronic hemiplegia received electrical stimulation therapy using the orthosis-type surface electrode stimulation device for 12 weeks. Training time was 30 min/day for the first weeks, and increased 30 min/day in every 4 weeks. Upper limb outcome measures included Brunnstrom stage, range of motion, Fugl-Meyer assessment and manual function test. Brain activation was measured using functional MRI. After therapy with therapeutic electrical stimulation (TES) for 12 weeks upper limb function improved in all cases. The results of brain activation showed two patterns. In the first, the stimulation produced an activity in the bilateral somatosensory cortices (SMC), which was seen to continue over time. The second, activation was bilateral and extensive before stimulation, but localized to the SMC after intervention. Treatment with TES using an orthosis-type electrode stimulation device improves upper limb function in chronic hemiplegia patients. The present findings suggest that there are not only efferent but also afferent effects that may promote central nervous system remodeling.

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Paired Associative Stimulation Using Brain-Computer Interfaces for Stroke Rehabilitation: A Pilot Study.

PubMed

Cho, Woosang; Sabathiel, Nikolaus; Ortner, Rupert; Lechner, Alexander; Irimia, Danut C; Allison, Brendan Z; Edlinger, Guenter; Guger, Christoph

2016-06-13

Conventional therapies do not provide paralyzed patients with closed-loop sensorimotor integration for motor rehabilitation. Paired associative stimulation (PAS) uses brain-computer interface (BCI) technology to monitor patients' movement imagery in real-time, and utilizes the information to control functional electrical stimulation (FES) and bar feedback for complete sensorimotor closed loop. To realize this approach, we introduce the recoveriX system, a hardware and software platform for PAS. After 10 sessions of recoveriX training, one stroke patient partially regained control of dorsiflexion in her paretic wrist. A controlled group study is planned with a new version of the recoveriX system, which will use a new FES system and an avatar instead of bar feedback.

Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

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.

The Gut Microbiome and the Brain

PubMed Central

Galland, Leo

2014-01-01

Abstract The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics. PMID:25402818

Fiber-array based optogenetic prosthetic system for stimulation therapy

NASA Astrophysics Data System (ADS)

Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

2012-02-01

Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

Extrinsic Embryonic Sensory Stimulation Alters Multimodal Behavior and Cellular Activation

PubMed Central

Markham, Rebecca G.; Shimizu, Toru; Lickliter, Robert

2009-01-01

Embryonic vision is generated and maintained by spontaneous neuronal activation patterns, yet extrinsic stimulation also sculpts sensory development. Because the sensory and motor systems are interconnected in embryogenesis, how extrinsic sensory activation guides multimodal differentiation is an important topic. Further, it is unknown whether extrinsic stimulation experienced near sensory sensitivity onset contributes to persistent brain changes, ultimately affecting postnatal behavior. To determine the effects of extrinsic stimulation on multimodal development, we delivered auditory stimulation to bobwhite quail groups during early, middle, or late embryogenesis, and then tested postnatal behavioral responsiveness to auditory or visual cues. Auditory preference tendencies were more consistently toward the conspecific stimulus for animals stimulated during late embryogenesis. Groups stimulated during middle or late embryogenesis showed altered postnatal species-typical visual responsiveness, demonstrating a persistent multimodal effect. We also examined whether auditory-related brain regions are receptive to extrinsic input during middle embryogenesis by measuring postnatal cellular activation. Stimulated birds showed a greater number of ZENK-immunopositive cells per unit volume of brain tissue in deep optic tectum, a midbrain region strongly implicated in multimodal function. We observed similar results in the medial and caudomedial nidopallia in the telencephalon. There were no ZENK differences between groups in inferior colliculus or in caudolateral nidopallium, avian analog to prefrontal cortex. To our knowledge, these are the first results linking extrinsic stimulation delivered so early in embryogenesis to changes in postnatal multimodal behavior and cellular activation. The potential role of competitive interactions between the sensory and motor systems is discussed. PMID:18777564

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

PubMed

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 be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Neuronal inhibition and synaptic plasticity of basal ganglia neurons in Parkinson's disease

PubMed Central

Milosevic, Luka; Kalia, Suneil K; Hodaie, Mojgan; Lozano, Andres M; Fasano, Alfonso; Popovic, Milos R; Hutchison, William D

2018-01-01

Abstract Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease symptoms. The therapeutic benefits of deep brain stimulation are frequency-dependent, but the underlying physiological mechanisms remain unclear. To advance deep brain stimulation therapy an understanding of fundamental mechanisms is critical. The objectives of this study were to (i) compare the frequency-dependent effects on cell firing in subthalamic nucleus and substantia nigra pars reticulata; (ii) quantify frequency-dependent effects on short-term plasticity in substantia nigra pars reticulata; and (iii) investigate effects of continuous long-train high frequency stimulation (comparable to conventional deep brain stimulation) on synaptic plasticity. Two closely spaced (600 µm) microelectrodes were advanced into the subthalamic nucleus (n = 27) and substantia nigra pars reticulata (n = 14) of 22 patients undergoing deep brain stimulation surgery for Parkinson’s disease. Cell firing and evoked field potentials were recorded with one microelectrode during stimulation trains from the adjacent microelectrode across a range of frequencies (1–100 Hz, 100 µA, 0.3 ms, 50–60 pulses). Subthalamic firing attenuated with ≥20 Hz (P < 0.01) stimulation (silenced at 100 Hz), while substantia nigra pars reticulata decreased with ≥3 Hz (P < 0.05) (silenced at 50 Hz). Substantia nigra pars reticulata also exhibited a more prominent increase in transient silent period following stimulation. Patients with longer silent periods after 100 Hz stimulation in the subthalamic nucleus tended to have better clinical outcome after deep brain stimulation. At ≥30 Hz the first evoked field potential of the stimulation train in substantia nigra pars reticulata was potentiated (P < 0.05); however, the average amplitude of the subsequent potentials was rapidly attenuated (P < 0.01). This is suggestive of synaptic facilitation followed by rapid depression. Paired pulse ratios calculated at the beginning of the train revealed that 20 Hz (P < 0.05) was the minimum frequency required to induce synaptic depression. Lastly, the average amplitude of evoked field potentials during 1 Hz pulses showed significant inhibitory synaptic potentiation after long-train high frequency stimulation (P < 0.001) and these increases were coupled with increased durations of neuronal inhibition (P < 0.01). The subthalamic nucleus exhibited a higher frequency threshold for stimulation-induced inhibition than the substantia nigra pars reticulata likely due to differing ratios of GABA:glutamate terminals on the soma and/or the nature of their GABAergic inputs (pallidal versus striatal). We suggest that enhancement of inhibitory synaptic plasticity, and frequency-dependent potentiation and depression are putative mechanisms of deep brain stimulation. Furthermore, we foresee that future closed-loop deep brain stimulation systems (with more frequent off stimulation periods) may benefit from inhibitory synaptic potentiation that occurs after high frequency stimulation. PMID:29236966

Non-invasive brain stimulation in children: applications and future directions

PubMed Central

Rajapakse, Thilinie; Kirton, Adam

2013-01-01

Transcranial magnetic stimulation (TMS) is a neurostimulation and neuromodulation technique that has provided over two decades of data in focal, non-invasive brain stimulation based on the principles of electromagnetic induction. Its minimal risk, excellent tolerability and increasingly sophisticated ability to interrogate neurophysiology and plasticity make it an enviable technology for use in pediatric research with future extension into therapeutic trials. While adult trials show promise in using TMS as a novel, non-invasive, non-pharmacologic diagnostic and therapeutic tool in a variety of nervous system disorders, its use in children is only just emerging. TMS represents an exciting advancement to better understand and improve outcomes from disorders of the developing brain. PMID:24163755

Activation of neurons in cardiovascular areas of cat brain stem affects spinal reflexes.

PubMed

Wu, W C; Wang, S D; Liu, J C; Horng, H T; Wayner, M J; Ma, J C; Chai, C Y

1994-01-01

In 65 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the effects of electrical stimulation and microinjection of sodium glutamate (0.25 M, 100-200 nl) in the pressor areas in the rostral brain stem on the evoked L5 ventral root response (EVRR) due to intermittent stimulation of sciatic afferents were compared to stimulating the dorsomedial (DM) and ventrolateral (VLM) medulla. In general, stimulating these rostral brain stem pressor areas including the diencephalon (DIC) and rostral pons (RP) produced increases in systemic arterial pressure (SAP). In most of the cases (85%) there were associated changes in the EVRR, predominantly a decrease in EVRR (72%). Stimulation of the midbrain (MB, principally in the periaqueductal grey) produced decreases in SAP and EVRR. Decreases in EVRR was observed in 91% of the DM and VLM stimulations in which an increase in SAP was produced. This EVRR inhibition was essentially unaltered after acute midcollicular decerebration. Increases in EVRR were also observed and occurred more often in the rostral brain stem than in the medulla. Since changes of both EVRR and SAP could be reproduced by microinjection of Glu into the cardiovascular-reactive areas of the brain stem, this suggests that neuronal perikarya in these areas are responsible for both actions. On some occasions, Glu induced changes in EVRR but not in SAP. This effect occurred more frequently in the rostral brain stem than in the medulla. The present data suggest that separate neuron population exist in the brain stem for the integration of SAP and spinal reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral Transcranial Direct Current Stimulation Reshapes Resting-State Brain Networks: A Magnetoencephalography Assessment

PubMed Central

Turco, Cristina; Di Pino, Giovanni; Arcara, Giorgio

2018-01-01

Transcranial direct current stimulation (tDCS) can noninvasively induce brain plasticity, and it is potentially useful to treat patients affected by neurological conditions. However, little is known about tDCS effects on resting-state brain networks, which are largely involved in brain physiological functions and in diseases. In this randomized, sham-controlled, double-blind study on healthy subjects, we have assessed the effect of bilateral tDCS applied over the sensorimotor cortices on brain and network activity using a whole-head magnetoencephalography system. Bilateral tDCS, with the cathode (−) centered over C4 and the anode (+) centered over C3, reshapes brain networks in a nonfocal fashion. Compared to sham stimulation, tDCS reduces left frontal alpha, beta, and gamma power and increases global connectivity, especially in delta, alpha, beta, and gamma frequencies. The increase of connectivity is consistent across bands and widespread. These results shed new light on the effects of tDCS and may be of help in personalizing treatments in neurological disorders. PMID:29593782

Brainstem stimulation increases functional connectivity of basal forebrain-paralimbic network in isoflurane-anesthetized rats.

PubMed

Pillay, Siveshigan; Liu, Xiping; Baracskay, Péter; Hudetz, Anthony G

2014-09-01

Brain states and cognitive-behavioral functions are precisely controlled by subcortical neuromodulatory networks. Manipulating key components of the ascending arousal system (AAS), via deep-brain stimulation, may help facilitate global arousal in anesthetized animals. Here we test the hypothesis that electrical stimulation of the oral part of the pontine reticular nucleus (PnO) under light isoflurane anesthesia, associated with loss of consciousness, leads to cortical desynchronization and specific changes in blood-oxygenation-level-dependent (BOLD) functional connectivity (FC) of the brain. BOLD signals were acquired simultaneously with frontal epidural electroencephalogram before and after PnO stimulation. Whole-brain FC was mapped using correlation analysis with seeds in major centers of the AAS. PnO stimulation produced cortical desynchronization, a decrease in δ- and θ-band power, and an increase in approximate entropy. Significant increases in FC after PnO stimulation occurred between the left nucleus Basalis of Meynert (NBM) as seed and numerous regions of the paralimbic network. Smaller increases in FC were present between the central medial thalamic nucleus and retrosplenium seeds and the left caudate putamen and NBM. The results suggest that, during light anesthesia, PnO stimulation preferentially modulates basal forebrain-paralimbic networks. We speculate that this may be a reflection of disconnected awareness.

Connectomics and other novel methods for examining neural systems.

PubMed

Wurtman, Richard J

2017-04-01

Novel approaches for studying the brain and relating its activities to mental phenomena have come into use during the past decade (Bargmann, 2015). These include both new laboratory methods - involving, among others, generation of isolated cells which retain neuronal characteristics in vivo; the selective stimulation of neurons by light in vivo; and direct electrical stimulation of specific brain regions to restore a system's balance of excitation and inhibition - and a new organizing principle, "connectomics", which recognizes that networks, and not simply a key nucleus or region, underlie most brain functions and malfunctions. Its application has already improved our comprehension of how the brain normally functions and our ability to help patients with such poorly treated neurologic and psychiatric diseases as Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Acupuncture, the limbic system, and the anticorrelated networks of the brain.

PubMed

Hui, Kathleen K S; Marina, Ovidiu; Liu, Jing; Rosen, Bruce R; Kwong, Kenneth K

2010-10-28

The study of the mechanism of acupuncture action was revolutionized by the use of functional magnetic resonance imaging (fMRI). Over the past decade, our fMRI studies of healthy subjects have contributed substantially to elucidating the central effect of acupuncture on the human brain. These studies have shown that acupuncture stimulation, when associated with sensations comprising deqi, evokes deactivation of a limbic-paralimbic-neocortical network, which encompasses the limbic system, as well as activation of somatosensory brain regions. These networks closely match the default mode network and the anti-correlated task-positive network described in the literature. We have also shown that the effect of acupuncture on the brain is integrated at multiple levels, down to the brainstem and cerebellum. Our studies support the hypothesis that the effect of acupuncture on the brain goes beyond the effect of attention on the default mode network or the somatosensory stimulation of acupuncture needling. The amygdala and hypothalamus, in particular, show decreased activation during acupuncture stimulation that is not commonly associated with default mode network activity. At the same time, our research shows that acupuncture stimulation needs to be done carefully, limiting stimulation when the resulting sensations are very strong or when sharp pain is elicited. When acupuncture induced sharp pain, our studies show that the deactivation was attenuated or reversed in direction. Our results suggest that acupuncture mobilizes the functionally anti-correlated networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response. In this work we also discuss multiple avenues of future research, including the role of neurotransmitters, the effect of different acupuncture techniques, and the potential clinical application of our research findings to disease states including chronic pain, major depression, schizophrenia, autism, and Alzheimer's disease. Published by Elsevier B.V.

Neuroprotection for the new millennium. Matchmaking pharmacology and technology

NASA Technical Reports Server (NTRS)

Andrews, R. J.

2001-01-01

A major theme of the 1990s in the pathophysiology of nervous system injury has been the multifactorial etiology of irreversible injury. Multiple causes imply multiple opportunities for therapeutic intervention--hence the abandonment of the "magic bullet" single pharmacologic agent for neuroprotection in favor of pharmacologic "cocktails". A second theme of the 1990s has been the progress in technology for neuroprotection, minimally- or non-invasive monitoring as well as treatment. Cardiac stenting has eliminated the need, in many cases, for open heart surgery; deep brain stimulation for Parkinson's disease has offered significant improvement in quality of life for many who had exhausted cocktail drug treatment for their disease. Deep brain stimulation of the subthalamic nucleus offers a novel treatment for Parkinson's disease where a technological advance may actually be an intervention with effects that are normally expected from pharmacologic agents. Rather than merely "jamming" the nervous system circuits involved in Parkinson's disease, deep brain stimulation of the subthalamic nucleus appears to improve the neurotransmitter imbalance that lies at the heart of Parkinson's disease. It may also slow the progression of the disease. Given the example of deep brain stimulation of the subthalamic nucleus for Parkinson's disease, in future one may expect other technological or "hardware" interventions to influence the programming or "software" of the nervous system's physiologic response in certain disease states.

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s disease

PubMed Central

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 approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson’s disease, and helps inform how adaptive deep brain stimulation might best be delivered. PMID:28334851

Solving the Orientation Specific Constraints in Transcranial Magnetic Stimulation by Rotating Fields

PubMed Central

Neef, Nicole E.; Agudelo-Toro, Andres; Rakhmilevitch, David; Paulus, Walter; Moses, Elisha

2014-01-01

Transcranial Magnetic Stimulation (TMS) is a promising technology for both neurology and psychiatry. Positive treatment outcome has been reported, for instance in double blind, multi-center studies on depression. Nonetheless, the application of TMS towards studying and treating brain disorders is still limited by inter-subject variability and lack of model systems accessible to TMS. The latter are required to obtain a deeper understanding of the biophysical foundations of TMS so that the stimulus protocol can be optimized for maximal brain response, while inter-subject variability hinders precise and reliable delivery of stimuli across subjects. Recent studies showed that both of these limitations are in part due to the angular sensitivity of TMS. Thus, a technique that would eradicate the need for precise angular orientation of the coil would improve both the inter-subject reliability of TMS and its effectiveness in model systems. We show here how rotation of the stimulating field relieves the angular sensitivity of TMS and provides improvements in both issues. Field rotation is attained by superposing the fields of two coils positioned orthogonal to each other and operated with a relative phase shift in time. Rotating field TMS (rfTMS) efficiently stimulates both cultured hippocampal networks and rat motor cortex, two neuronal systems that are notoriously difficult to excite magnetically. This opens the possibility of pharmacological and invasive TMS experiments in these model systems. Application of rfTMS to human subjects overcomes the orientation dependence of standard TMS. Thus, rfTMS yields optimal targeting of brain regions where correct orientation cannot be determined (e.g., via motor feedback) and will enable stimulation in brain regions where a preferred axonal orientation does not exist. PMID:24505266

Spectral properties of the temporal evolution of brain network structure.

PubMed

Wang, Rong; Zhang, Zhen-Zhen; Ma, Jun; Yang, Yong; Lin, Pan; Wu, Ying

2015-12-01

The temporal evolution properties of the brain network are crucial for complex brain processes. In this paper, we investigate the differences in the dynamic brain network during resting and visual stimulation states in a task-positive subnetwork, task-negative subnetwork, and whole-brain network. The dynamic brain network is first constructed from human functional magnetic resonance imaging data based on the sliding window method, and then the eigenvalues corresponding to the network are calculated. We use eigenvalue analysis to analyze the global properties of eigenvalues and the random matrix theory (RMT) method to measure the local properties. For global properties, the shifting of the eigenvalue distribution and the decrease in the largest eigenvalue are linked to visual stimulation in all networks. For local properties, the short-range correlation in eigenvalues as measured by the nearest neighbor spacing distribution is not always sensitive to visual stimulation. However, the long-range correlation in eigenvalues as evaluated by spectral rigidity and number variance not only predicts the universal behavior of the dynamic brain network but also suggests non-consistent changes in different networks. These results demonstrate that the dynamic brain network is more random for the task-positive subnetwork and whole-brain network under visual stimulation but is more regular for the task-negative subnetwork. Our findings provide deeper insight into the importance of spectral properties in the functional brain network, especially the incomparable role of RMT in revealing the intrinsic properties of complex systems.

Spectral properties of the temporal evolution of brain network structure

NASA Astrophysics Data System (ADS)

Wang, Rong; Zhang, Zhen-Zhen; Ma, Jun; Yang, Yong; Lin, Pan; Wu, Ying

2015-12-01

The temporal evolution properties of the brain network are crucial for complex brain processes. In this paper, we investigate the differences in the dynamic brain network during resting and visual stimulation states in a task-positive subnetwork, task-negative subnetwork, and whole-brain network. The dynamic brain network is first constructed from human functional magnetic resonance imaging data based on the sliding window method, and then the eigenvalues corresponding to the network are calculated. We use eigenvalue analysis to analyze the global properties of eigenvalues and the random matrix theory (RMT) method to measure the local properties. For global properties, the shifting of the eigenvalue distribution and the decrease in the largest eigenvalue are linked to visual stimulation in all networks. For local properties, the short-range correlation in eigenvalues as measured by the nearest neighbor spacing distribution is not always sensitive to visual stimulation. However, the long-range correlation in eigenvalues as evaluated by spectral rigidity and number variance not only predicts the universal behavior of the dynamic brain network but also suggests non-consistent changes in different networks. These results demonstrate that the dynamic brain network is more random for the task-positive subnetwork and whole-brain network under visual stimulation but is more regular for the task-negative subnetwork. Our findings provide deeper insight into the importance of spectral properties in the functional brain network, especially the incomparable role of RMT in revealing the intrinsic properties of complex systems.

Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

PubMed Central

Chang, Su-Youne; Kimble, Christopher J.; Kim, Inyong; Paek, Seungleal B.; Kressin, Kenneth R.; Boesche, Joshua B.; Whitlock, Sidney V.; Eaker, Diane R.; Kasasbeh, Aimen; Horne, April E.; Blaha, Charles D.; Bennet, Kevin E.; Lee, Kendall H.

2014-01-01

Object Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS “smart” device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS). Methods To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between −0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of −0.4 V between scans. Results By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency. Conclusions Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application. PMID:24116724

Miniaturized neural sensing and optogenetic stimulation system for behavioral studies in the rat

NASA Astrophysics Data System (ADS)

Kim, Min Hyuck; Nam, Ilho; Ryu, Youngki; Wellman, Laurie W.; Sanford, Larry D.; Yoon, Hargsoon

2015-04-01

Real time sensing of localized electrophysiological and neurochemical signals associated with spontaneous and evoked neural activity is critically important for understanding neural networks in the brain. Our goal is to enhance the functionality and flexibility of a neural sensing and stimulation system for the observation of brain activity that will enable better understanding from the level of individual cells to that of global structures. We have thus developed a miniaturized electronic system for in-vivo neurotransmitter sensing and optogenetic stimulation amenable to behavioral studies in the rat. The system contains a potentiostat, a data acquisition unit, a control unit, and a wireless data transfer unit. For the potentiostat, we applied embedded op-amps to build single potential amperometry for electrochemical sensing of dopamine. A light emitting diode is controlled by a microcontroller and pulse width modulation utilized to control optogenetic stimulation within a sub-millisecond level. In addition, this proto-typed electronic system contains a Bluetooth module for wireless data communication. In the future, an application-specific integrated circuit (ASIC) will be designed for further miniaturization of the system.

A portable telemetry system for brain stimulation and neuronal activity recording in freely behaving small animals.

PubMed

Ye, Xuesong; Wang, Peng; Liu, Jun; Zhang, Shaomin; Jiang, Jun; Wang, Qingbo; Chen, Weidong; Zheng, Xiaoxiang

2008-09-30

A portable multi-channel telemetry system which can be used for brain stimulation and neuronal activity recording in freely behaving small animals is described here. This system consists of three major components of headstage, backpack and portable Personal Digital Assistant (PDA). The headstage contains high precision instrument amplifiers with high input impedance. The backpack is comprised of two parts: (1) a main board (size: 36 mm x 22 mm x 3.5 mm and weight: 40 g with batteries, 20 g without), with current/voltage stimulator and special circuit suitable for neuronal activity recording and (2) and a bluetooth transceiver, with a high data transmission rate up to 70 kb/s, suitable for downloading stimulation commands and uploading acquired data. We recorded neuronal activities of the primary motor area of a freely behaving rat with 12-bit resolution at 12 k samples/s. The recorded data and analysis results showed that the system was successful by comparing with the commercial equipment Cerebus 128-Channel Data Acquisition System (Cyberkinetics Inc.). Using the PDA, we can control stimulation and recording. It provides a flexible method to do some research work in the circumstances where other approaches would be difficult or impossible.

Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus and Trigeminal Nerves

PubMed Central

Mercante, Beniamina; Rangon, Claire-Marie

2018-01-01

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions. PMID:29361732

Rechargeable internal neural stimulators--is there a problem with efficacy?

PubMed

Harries, Anwen M; Major, Shannon; Sandhu, Mandeep; Honey, Christopher R

2012-01-01

With the advent of rechargeable internal neural stimulators (rINS) for deep brain stimulation, our aim was to survey patient satisfaction and clinical efficacy in an early cohort of patients receiving this new technology. This is an observational study on nine patients with rINS. All patients had initially received non-rechargeable INS with established efficacy of their deep brain stimulation system for either dystonia or pain. Patient satisfaction and efficacy with their rINS were established by completion of a questionnaire, a quality of life assessment (SF-36), and calculation of the total electrical energy delivered (TEED) by the rINS. A reduction in efficacy of their rINS was noticed in 22% of patients. In 78% of patients, there was a problem with recharging their rINS because of poor contact. Two patients (22%) felt that recharging the rINS interfered with their lives and it was a daily reminder that they had a deep brain stimulator system in situ. Eight out of nine patients (89%), however, would recommend to other patients to have an rINS. Most patients were happy with their rechargeable internal neural stimulator. A reduction in efficacy was noticed in 22% of patients, which is similar to the proportion of patients noticing a reduction in efficacy when replacing with a non-rechargeable system. Thus, all patients require close monitoring post-replacement of rINS, in case possible adjustment of parameters is required. © 2011 International Neuromodulation Society.

Induction of panic attack by stimulation of the ventromedial hypothalamus.

PubMed

Wilent, W Bryan; Oh, Michael Y; Buetefisch, Cathrin M; Bailes, Julian E; Cantella, Diane; Angle, Cindy; Whiting, Donald M

2010-06-01

Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.

Neural signal processing and closed-loop control algorithm design for an implanted neural recording and stimulation system.

PubMed

Hamilton, Lei; McConley, Marc; Angermueller, Kai; Goldberg, David; Corba, Massimiliano; Kim, Louis; Moran, James; Parks, Philip D; Sang Chin; Widge, Alik S; Dougherty, Darin D; Eskandar, Emad N

2015-08-01

A fully autonomous intracranial device is built to continually record neural activities in different parts of the brain, process these sampled signals, decode features that correlate to behaviors and neuropsychiatric states, and use these features to deliver brain stimulation in a closed-loop fashion. In this paper, we describe the sampling and stimulation aspects of such a device. We first describe the signal processing algorithms of two unsupervised spike sorting methods. Next, we describe the LFP time-frequency analysis and feature derivation from the two spike sorting methods. Spike sorting includes a novel approach to constructing a dictionary learning algorithm in a Compressed Sensing (CS) framework. We present a joint prediction scheme to determine the class of neural spikes in the dictionary learning framework; and, the second approach is a modified OSort algorithm which is implemented in a distributed system optimized for power efficiency. Furthermore, sorted spikes and time-frequency analysis of LFP signals can be used to generate derived features (including cross-frequency coupling, spike-field coupling). We then show how these derived features can be used in the design and development of novel decode and closed-loop control algorithms that are optimized to apply deep brain stimulation based on a patient's neuropsychiatric state. For the control algorithm, we define the state vector as representative of a patient's impulsivity, avoidance, inhibition, etc. Controller parameters are optimized to apply stimulation based on the state vector's current state as well as its historical values. The overall algorithm and software design for our implantable neural recording and stimulation system uses an innovative, adaptable, and reprogrammable architecture that enables advancement of the state-of-the-art in closed-loop neural control while also meeting the challenges of system power constraints and concurrent development with ongoing scientific research designed to define brain network connectivity and neural network dynamics that vary at the individual patient level and vary over time.

Final Paper DAT Cognitive Art Therapy System

ERIC Educational Resources Information Center

Jacobson, Eric

2009-01-01

Del Giacco Art Therapy is a cognitive art therapy process that focuses on stimulating the mental sensory systems and working to stabilize the nervous system and create new neural connections in the brain. This system was created by Maureen Del Giacco, Phd. after recovering from her own traumatic brain injury and is based on extensive research of…

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

PubMed Central

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

PubMed

Li, Guangye; Zhang, Dingguo

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

A fast stimulability screening protocol for neuronal cultures on microelectrode arrays.

PubMed

Kapucu, Fikret E; Tanskanen, Jarno M A; Yuan, Yuting; Hyttinen, Jari A K

2015-01-01

Microelectrode arrays (MEAs) are used to study the electrical activity in brain slices and neuronal cultures. MEA experiments for the analysis of electrical stimulation responses require the tissue or culture to be prone to stimulation. For brain slices, potential stimulation sites may be directly visible in microscope, in which case the determination of stimulability at those locations is sufficient. In unstructured neuronal cultures, potential stimulation sites may not be known a priori, and spatial stimulability screening should be performed. Considering, e.g., 59 microelectrode sites, each to be stimulated several times, may result in long screening times, unacceptable with a MEA system without an integrated CO2 incubator, or in high stimulation effects on the networks. Here, we describe an implementation of a fast stimulation protocol employing pseudorandom stimulation site switching aiming at alleviating the network effects of the stimulability screening. In this paper, we show the usability of the proposed protocol by first detecting stimulable locations and subsequently apply repeated stimulation on the identified potentially stimulable locations to observe an exemplary neuronal pathway.

Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

PubMed Central

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

Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone.

PubMed

Harazin, András; Bocsik, Alexandra; Barna, Lilla; Kincses, András; Váradi, Judit; Fenyvesi, Ferenc; Tubak, Vilmos; Deli, Maria A; Vecsernyés, Miklós

2018-01-01

The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB.

Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone

PubMed Central

Barna, Lilla; Kincses, András; Váradi, Judit; Fenyvesi, Ferenc; Tubak, Vilmos

2018-01-01

The blood–brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-κB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB. PMID:29780671

Variability in Cortical Representations of Speech Sound Perception

ERIC Educational Resources Information Center

Boatman, Dana F.

2007-01-01

Recent brain mapping studies have provided new insights into the cortical systems that mediate human speech perception. Electrocortical stimulation mapping (ESM) is a brain mapping method that is used clinically to localize cortical functions in neurosurgical patients. Recent ESM studies have yielded new insights into the cortical systems that…

Simulation of fMRI signals to validate dynamic causal modeling estimation

NASA Astrophysics Data System (ADS)

Anandwala, Mobin; Siadat, Mohamad-Reza; Hadi, Shamil M.

2012-03-01

Through cognitive tasks certain brain areas are activated and also receive increased blood to them. This is modeled through a state system consisting of two separate parts one that deals with the neural node stimulation and the other blood response during that stimulation. The rationale behind using this state system is to validate existing analysis methods such as DCM to see what levels of noise they can handle. Using the forward Euler's method this system was approximated in a series of difference equations. What was obtained was the hemodynamic response for each brain area and this was used to test an analysis tool to estimate functional connectivity between each brain area with a given amount of noise. The importance of modeling this system is to not only have a model for neural response but also to compare to actual data obtained through functional imaging scans.

Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: a tDCS-fMRI study.

PubMed

Weber, Matthew J; Messing, Samuel B; Rao, Hengyi; Detre, John A; Thompson-Schill, Sharon L

2014-08-01

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. Copyright © 2014 Wiley Periodicals, Inc.

Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain.

PubMed

Hungen, K V; Roberts, S; Hill, D F

1975-08-22

Investigations were carried out on the interactions of the hallucinogenic drug, D-lysergic acid diethylamide (D-LSD), and other serotonin antagonists with catecholamine-sensitive adenylate cyclase systems in cell-free preparations from different regions of rat brain. In equimolar concentration, D-LSD, 2-brono-D-lysergic acid diethylamide (BOL), or methysergide (UML) strongly blocked maximal stimulation of adenylate cyclase activity by either norepinephrine or dopamine in particulate preparations from cerebral cortices of young adult rats. D-LSD also eliminated the stimulation of adenylate cyclase activity of equimolar concentrations of norepinephrine or dopamine in particulate preparations from rat hippocampus. The effects of this hallucinogenic agent on adenylate cyclase activity were most striking in particulate preparations from corpus striatum. Thus, in 10 muM concentration, D-LSD not only completely eradicated the response to 10 muM dopamine in these preparations but also consistently stimulated adenylate cyclase activity. L-LSD (80 muM) was without effect. Significant activation of striatal adenylate cyclase was produced by 0.1 muM D-LSD. Activation of striatal adenylate cyclase of either D-LSD or dopamine was strongly blocked by the dopamine-blocking agents trifluoperazine, thioridazine, chlorpromazine, and haloperidol. The stimulatory effects of D-LSD and dopamine were also inhibited by the serotonin-blocking agents, BOL, 1-methyl-D-lysergic acid diethylamide (MLD), and cyproheptadine, but not by the beta-adrenergic-blocking agent, propranolol. However, these serotonin antagonists by themselves were incapable of stimulating adenylate cyclase activity in the striatal preparations. Several other hallucinogens, which were structurally related to serotonin, were also inactive in this regard, e.g., mescaline, N,N-dimethyltryptamine, psilocin and bufotenine. Serotonin itself produced a small stimulation of adenylate cyclase activity in striatal preparations and, in relatively high concentration (100 muM), partially blocked the activation by 10 muM dopamine, but was without effect on the stimulation by 10 muM D-LSD. The present results indicate that serotonin antagonists, in general, are potent inhibitors of catecholamine-induced stimulation of adenylate cyclase systems in brain cell-free preparations. In addition, these results, coupled with earlier findings on the capacity of D-LSD to interact with serotonin-sensitive adenylate cyclase systems from rat brain23,24 and other neural systems16, strongly suggest that this hallucinogenic agent is capable of acting as an agonist at central dopamine and serotonin receptors, as well as functioning as an antagonist at dopamine, norepinephrine, and serotonin receptors in the brain.

Plasticity in the Developing Brain: Implications for Rehabilitation

ERIC Educational Resources Information Center

Johnston, Michael V.

2009-01-01

Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive…

Laser stimulation for pain research

NASA Astrophysics Data System (ADS)

Clark, Stuart; Dickinson, Mark R.; King, Terence A.; Jones, Anthony; Chen, Andrew; Derbyshire, Stuart; Townsend, D. W.; Kinahan, Paul E.; Mintun, M. A.; Nichols, T.

1996-01-01

Pain is a serious medical problem; it inflicts huge economic loss and personal suffering. Pain signals are conducted via small, non- and partially myelinated A-delta and C nerve fibers and lasers are particularly well suited to stimulating these fibers. Large myelinated fibers convey touch and vibration information and these fibers are also discharged when contact thermodes and other touch pain stimuli are used and this would give a more muddled signal for functional imaging experiments. The advantages of lasers over conventional methods of pain stimulation are good temporal resolution, no variable parameters are involved such as contact area and they give very reproducible results. Accurate inter-stimulus changes can be achieved by computer control of the laser pulse duration, pulse height and repetition rate and this flexibility enables complex stimulation paradigms to be realized. We present a flexible carbon dioxide laser system designed to generate these stimuli for the study of human cerebral pain responses. We discuss the advantages within research of this system over other methods of pain stimulation such as thermal, electrical and magnetic. The stimulator is used in conjunction with functional magnetic resonance imaging, positron emission tomography and electrophysiological methods of imaging the brain's activity. This combination is a powerful tool for the study of pain-induced activity in different areas of the brain. An accurate understanding of the brain's response to pain will help in research into the areas of rheumatoid arthritis and chronic back pain.

Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

PubMed

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.

Transcranial magnetic stimulation assisted by neuronavigation of magnetic resonance images

NASA Astrophysics Data System (ADS)

Viesca, N. Angeline; Alcauter, S. Sarael; Barrios, A. Fernando; González, O. Jorge J.; Márquez, F. Jorge A.

2012-10-01

Technological advance has improved the way scientists and doctors can learn about the brain and treat different disorders. A non-invasive method used for this is Transcranial Magnetic Stimulation (TMS) based on neuron excitation by electromagnetic induction. Combining this method with functional Magnetic Resonance Images (fMRI), it is intended to improve the localization technique of cortical brain structures by designing an extracranial localization system, based on Alcauter et al. work.

Electro-Quasistatic Simulations in Bio-Systems Engineering and Medical Engineering

NASA Astrophysics Data System (ADS)

van Rienen, U.; Flehr, J.; Schreiber, U.; Schulze, S.; Gimsa, U.; Baumann, W.; Weiss, D. G.; Gimsa, J.; Benecke, R.; Pau, H.-W.

2005-05-01

Slowly varying electromagnetic fields play a key role in various applications in bio-systems and medical engineering. Examples are the electric activity of neurons on neurochips used as biosensors, the stimulating electric fields of implanted electrodes used for deep brain stimulation in patients with Morbus Parkinson and the stimulation of the auditory nerves in deaf patients, respectively. In order to simulate the neuronal activity on a chip it is necessary to couple Maxwell's and Hodgkin-Huxley's equations. First numerical results for a neuron coupling to a single electrode are presented. They show a promising qualitative agreement with the experimentally recorded signals. Further, simulations are presented on electrodes for deep brain stimulation in animal experiments where the question of electrode ageing and energy deposition in the surrounding tissue are of major interest. As a last example, electric simulations for a simple cochlea model are presented comparing the field in the skull bones for different electrode types and stimulations in different positions.

Response properties of nucleus reticularis lateralis neurons after electroacupuncture stimulation in rats.

PubMed

Moritaka, Kentaro; Zeredo, Jorge L; Kimoto, Mari; Nasution, Fajar H; Hirano, Takafumi; Toda, Kazuo

2010-01-01

A descending inhibitory mechanism from the periaqueductal gray (PAG) to the spinal cord through the nucleus raphe magnus (NRM) is strongly involved in endogenous analgesic system produced by acupuncture stimulation. In addition to the PAG to NRM system which descends in the medial pathway of the brain stem, the nucleus reticularis lateralis (NRL) situated in the lateral part of the brain stem is reported to play an important role in modulating centrifugal antinociceptive action. In the present study, to clarify the role of NRL in acupuncture analgesia, we investigated the response properties of NRL neurons to acupuncture stimulation. The majority of NRM-projecting NRL neurons were inhibited by electroacupuncture stimulation. This effect was antagonized by ionophoretic application of naloxone, indicating that endogenous opioids act directly onto these NRL neurons. By contrast, about half of spinal projecting NRL neurons were excited by electroacupuncture stimulation, suggesting that part of the NRL neurons may modulate pain transmission directly at the spinal level.

Ownership of an artificial limb induced by electrical brain stimulation

PubMed Central

Collins, Kelly L.; Cronin, Jeneva; Olson, Jared D.; Ehrsson, H. Henrik; Ojemann, Jeffrey G.

2017-01-01

Replacing the function of a missing or paralyzed limb with a prosthetic device that acts and feels like one’s own limb is a major goal in applied neuroscience. Recent studies in nonhuman primates have shown that motor control and sensory feedback can be achieved by connecting sensors in a robotic arm to electrodes implanted in the brain. However, it remains unknown whether electrical brain stimulation can be used to create a sense of ownership of an artificial limb. In this study on two human subjects, we show that ownership of an artificial hand can be induced via the electrical stimulation of the hand section of the somatosensory (SI) cortex in synchrony with touches applied to a rubber hand. Importantly, the illusion was not elicited when the electrical stimulation was delivered asynchronously or to a portion of the SI cortex representing a body part other than the hand, suggesting that multisensory integration according to basic spatial and temporal congruence rules is the underlying mechanism of the illusion. These findings show that the brain is capable of integrating “natural” visual input and direct cortical-somatosensory stimulation to create the multisensory perception that an artificial limb belongs to one’s own body. Thus, they serve as a proof of concept that electrical brain stimulation can be used to “bypass” the peripheral nervous system to induce multisensory illusions and ownership of artificial body parts, which has important implications for patients who lack peripheral sensory input due to spinal cord or nerve lesions. PMID:27994147

Violence, mental illness, and the brain – A brief history of psychosurgery: Part 2 – From the limbic system and cingulotomy to deep brain stimulation

PubMed Central

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

Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease.

PubMed

Heo, Man Seung; Moon, Hyun Seok; Kim, Hee Chan; Park, Hyung Woo; Lim, Young Hoon; Paek, Sun Ha

2015-03-01

The purpose of this study to develop new deep-brain stimulation system for long-term use in animals, in order to develop a variety of neural prostheses. Our system has two distinguished features, which are the fully implanted system having wearable wireless power transfer and ability to change the parameter of stimulus parameter. It is useful for obtaining a variety of data from a long-term experiment. To validate our system, we performed pre-clinical test in Parkinson's disease-rat models for 4 weeks. Through the in vivo test, we observed the possibility of not only long-term implantation and stability, but also free movement of animals. We confirmed that the electrical stimulation neither caused any side effect nor damaged the electrodes. We proved possibility of our system to conduct the long-term pre-clinical test in variety of parameter, which is available for development of neural prostheses.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

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.

Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

PubMed Central

Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

2014-01-01

Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies. PMID:24917788

Expression of c-fos gene in central nervous system of adult medaka (Oryzias latipes) after hypergravity stimulation

NASA Astrophysics Data System (ADS)

Shimomura, S.; Ijiri, K.

The immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brain. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3G hypergravity by centrifugation. Investigation of c-fos mRNA expression showed that c-fos mRNA significantly increased 30 minutes after a start of 3G exposure. The distribution of its transcripts within brains was analyzed by an in situ hybridization method. The 3G-treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, posterior octavu nucleus, nucleus tangentialis and inferior olive. Our results established the method to trace the activated area in the fish brain following gravity stimulation. The method will be a useful tool for understanding gravity perception in the brain.

Nonsomatotopic organization of the higher motor centers in octopus.

PubMed

Zullo, Letizia; Sumbre, German; Agnisola, Claudio; Flash, Tamar; Hochner, Binyamin

2009-10-13

Hyperredundant limbs with a virtually unlimited number of degrees of freedom (DOFs) pose a challenge for both biological and computational systems of motor control. In the flexible arms of the octopus, simplification strategies have evolved to reduce the number of controlled DOFs. Motor control in the octopus nervous system is hierarchically organized. A relatively small central brain integrates a huge amount of visual and tactile information from the large optic lobes and the peripheral nervous system of the arms and issues commands to lower motor centers controlling the elaborated neuromuscular system of the arms. This unique organization raises new questions on the organization of the octopus brain and whether and how it represents the rich movement repertoire. We developed a method of brain microstimulation in freely behaving animals and stimulated the higher motor centers-the basal lobes-thus inducing discrete and complex sets of movements. As stimulation strength increased, complex movements were recruited from basic components shared by different types of movement. We found no stimulation site where movements of a single arm or body part could be elicited. Discrete and complex components have no central topographical organization but are distributed over wide regions.

Autonomic hyperreflexia

MedlinePlus

... mistakenly attacks part of the nervous system) Side effects of some medicines Severe head trauma and other brain injuries Subarachnoid hemorrhage (a form of brain bleeding) Use of illegal stimulant drugs such as cocaine and amphetamines Symptoms Symptoms can include any of ...

Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.

PubMed

Huang, Wei-Chen; Lo, Yu-Chih; Chu, Chao-Yi; Lai, Hsin-Yi; Chen, You-Yin; Chen, San-Yuan

2017-04-01

Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl 2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn 2+ . In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn 2+ ions, so that the system can release Mn 2+ ions rather than MnCl 2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2013-09-01

implemented to significantly decrease the IIR system response time, especially when artifacts were highly reproducible in consecutive stimulation...cycles. The proposed system architecture was hardware- implemented on a field- programmable gate array (FPGA) and tested using two sets of prerecorded...its FPGA implementation and testing with prerecorded neural datasets are reported in a manuscript currently in press with the IEEE Transactions on

Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

PubMed

Karamintziou, Sofia D; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G; Tagaris, George A; Sakas, Damianos E; Polychronaki, Georgia E; Tsirogiannis, George L; David, Olivier; Nikita, Konstantina S

2017-01-01

Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

Optimized temporal pattern of brain stimulation designed by computational evolution

PubMed Central

Brocker, David T.; Swan, Brandon D.; So, Rosa Q.; Turner, Dennis A.; Gross, Robert E.; Grill, Warren M.

2017-01-01

Brain stimulation is a promising therapy for several neurological disorders, including Parkinson’s disease. Stimulation parameters are selected empirically and are limited to the frequency and intensity of stimulation. We used the temporal pattern of stimulation as a novel parameter of deep brain stimulation to ameliorate symptoms in a parkinsonian animal model and in humans with Parkinson’s disease. We used model-based computational evolution to optimize the stimulation pattern. The optimized pattern produced symptom relief comparable to that from standard high-frequency stimulation (a constant rate of 130 or 185 Hz) and outperformed frequency-matched standard stimulation in the parkinsonian rat and in patients. Both optimized and standard stimulation suppressed abnormal oscillatory activity in the basal ganglia of rats and humans. The results illustrate the utility of model-based computational evolution to design temporal pattern of stimulation to increase the efficiency of brain stimulation in Parkinson’s disease, thereby requiring substantially less energy than traditional brain stimulation. PMID:28053151

A Study of the Effectiveness of Sensory Integration Therapy on Neuro-Physiological Development

ERIC Educational Resources Information Center

Reynolds, Christopher; Reynolds, Kathleen Sheena

2010-01-01

Background: Sensory integration theory proposes that because there is plasticity within the central nervous system (the brain is moldable) and because the brain consists of systems that are hierarchically organised, it is possible to stimulate and improve neuro-physiological processing and integration and thereby increase learning capacity.…

[A wireless smart home system based on brain-computer interface of steady state visual evoked potential].

PubMed

Zhao, Li; Xing, Xiao; Guo, Xuhong; Liu, Zehua; He, Yang

2014-10-01

Brain-computer interface (BCI) system is a system that achieves communication and control among humans and computers and other electronic equipment with the electroencephalogram (EEG) signals. This paper describes the working theory of the wireless smart home system based on the BCI technology. We started to get the steady-state visual evoked potential (SSVEP) using the single chip microcomputer and the visual stimulation which composed by LED lamp to stimulate human eyes. Then, through building the power spectral transformation on the LabVIEW platform, we processed timely those EEG signals under different frequency stimulation so as to transfer them to different instructions. Those instructions could be received by the wireless transceiver equipment to control the household appliances and to achieve the intelligent control towards the specified devices. The experimental results showed that the correct rate for the 10 subjects reached 100%, and the control time of average single device was 4 seconds, thus this design could totally achieve the original purpose of smart home system.

Feasibility of a Hybrid Brain-Computer Interface for Advanced Functional Electrical Therapy

PubMed Central

Savić, Andrej M.; Malešević, Nebojša M.; Popović, Mirjana B.

2014-01-01

We present a feasibility study of a novel hybrid brain-computer interface (BCI) system for advanced functional electrical therapy (FET) of grasp. FET procedure is improved with both automated stimulation pattern selection and stimulation triggering. The proposed hybrid BCI comprises the two BCI control signals: steady-state visual evoked potentials (SSVEP) and event-related desynchronization (ERD). The sequence of the two stages, SSVEP-BCI and ERD-BCI, runs in a closed-loop architecture. The first stage, SSVEP-BCI, acts as a selector of electrical stimulation pattern that corresponds to one of the three basic types of grasp: palmar, lateral, or precision. In the second stage, ERD-BCI operates as a brain switch which activates the stimulation pattern selected in the previous stage. The system was tested in 6 healthy subjects who were all able to control the device with accuracy in a range of 0.64–0.96. The results provided the reference data needed for the planned clinical study. This novel BCI may promote further restoration of the impaired motor function by closing the loop between the “will to move” and contingent temporally synchronized sensory feedback. PMID:24616644

Deep brain stimulation surgery for alcohol addiction.

PubMed

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.

75 FR 4407 - The Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-27

... premarket approval application for the Deep Brain Stimulation System for Epilepsy sponsored by Medtronic...-onset seizures (affecting only a part of the brain when they begin), with or without secondary... a partial-onset seizure that later spreads to the whole brain. ``Refractory'' to antiepileptic...

Brain-derived neurotrophic factor and its receptors in Bergmann glia cells.

PubMed

Poblete-Naredo, Irais; Guillem, Alain M; Juárez, Claudia; Zepeda, Rossana C; Ramírez, Leticia; Caba, Mario; Hernández-Kelly, Luisa C; Aguilera, José; López-Bayghen, Esther; Ortega, Arturo

2011-12-01

Brain-derived neurotrophic factor is an abundant and widely distributed neurotrophin expressed in the Central Nervous System. It is critically involved in neuronal differentiation and survival. The expression of brain-derived neurotrophic factor and that of its catalytic active cognate receptor (TrkB) has been extensively studied in neuronal cells but their expression and function in glial cells is still controversial. Despite of this fact, brain-derived neurotrophic factor is released from astrocytes upon glutamate stimulation. A suitable model to study glia/neuronal interactions, in the context of glutamatergic synapses, is the well-characterized culture of chick cerebellar Bergmann glia cells. Using, this system, we show here that BDNF and its functional receptor are present in Bergmann glia and that BDNF stimulation is linked to the activation of the phosphatidyl-inositol 3 kinase/protein kinase C/mitogen-activated protein kinase/Activator Protein-1 signaling pathway. Accordingly, reverse transcription-polymerase chain reaction (RT-PCR) experiments predicted the expression of full-length and truncated TrkB isoforms. Our results suggest that Bergmann glia cells are able to express and respond to BDNF stimulation favoring the notion of their pivotal role in neuroprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

PubMed Central

Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

2014-01-01

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil.

PubMed

Feifel, David; Pappas, Katherine

2016-10-04

Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression. Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

Tractography patterns of subthalamic nucleus deep brain stimulation.

PubMed

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 outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

PubMed

Geiko, V V; Vorob'eva, T M; Berchenko, O G; Epstein, O I

2003-01-01

The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

Conscious brain-to-brain communication in humans using non-invasive technologies.

PubMed

Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

2014-01-01

Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies

PubMed Central

Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L.; Pascual-Leone, Alvaro; Ruffini, Giulio

2014-01-01

Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. PMID:25137064

Deep-brain-stimulation does not impair deglutition in Parkinson's disease.

PubMed

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.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

PubMed

Boes, Aaron D; Kelly, Michael S; Trapp, Nicholas T; Stern, Adam P; Press, Daniel Z; Pascual-Leone, Alvaro

2018-04-24

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation

PubMed Central

Xu, Yi; Hou, Qing-hua; Russell, Shawn D.; Bennett, Bradford C.; Sellers, Andrew J.; Lin, Qiang; Huang, Dong-feng

2015-01-01

Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques. PMID:26889202

Oscillatory frontal theta responses are increased upon bisensory stimulation.

PubMed

Sakowitz, O W; Schürmann, M; Başar, E

2000-05-01

To investigate the functional correlation of oscillatory EEG components with the interaction of sensory modalities following simultaneous audio-visual stimulation. In an experimental study (15 subjects) we compared auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) to bimodal evoked potentials (BEPs; simultaneous auditory and visual stimulation). BEPs were assumed to be brain responses to complex stimuli as a marker for intermodal associative functioning. Frequency domain analysis of these EPs showed marked theta-range components in response to bimodal stimulation. These theta components could not be explained by linear addition of the unimodal responses in the time domain. Considering topography the increased theta-response showed a remarkable frontality in proximity to multimodal association cortices. Referring to methodology we try to demonstrate that, even if various behavioral correlates of brain oscillations exist, common patterns can be extracted by means of a systems-theoretical approach. Serving as an example of functionally relevant brain oscillations, theta responses could be interpreted as an indicator of associative information processing.

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

PubMed Central

Johansson, Johannes; Wårdell, Karin; Hemm, Simone

2018-01-01

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

Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors.

PubMed

Nader, Joëlle; Rapino, Cinzia; Gennequin, Benjamin; Chavant, Francois; Francheteau, Maureen; Makriyannis, Alexandros; Duranti, Andrea; Maccarrone, Mauro; Solinas, Marcello; Thiriet, Nathalie

2014-12-01

Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed to increase their endogenous tone. In this study, we evaluated whether ECS stimulation could reduce the neurotoxicity of high doses of methamphetamine on the dopamine system. We found that methamphetamine alters the levels of the major endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in the striatum, suggesting that the ECS participates in the brain responses to methamphetamine. Δ(9)-tetrahydrocannabinol (THC), a cannabis-derived agonist of both CB1 and CB2 cannabinoid receptors, or inhibitors of the main enzymes responsible for the degradation of AEA and 2-AG (URB597 and JZL184, respectively), blunted the decrease in striatal protein levels of tyrosine hydroxylase induced by methamphetamine. In addition, antagonists of CB2, but not of CB1, blocked the preventive effects of URB597 and JZL184, suggesting that only the former receptor subtype is engaged in neuroprotection exerted by ECS stimulation. Finally, we found that methamphetamine increases striatal levels of the cytokine tumor necrosis factor alpha, an effect that was blocked by ECS stimulation. Altogether, our results indicate that stimulation of ECS prior to the administration of an overdose of methamphetamine considerably reduces the neurotoxicity of the drug through CB2 receptor activation and highlight a protective function for the ECS against the toxicity induced by drugs and other external insults to the brain. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

PubMed Central

Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

2015-01-01

Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

Amino Acids That Centrally Influence Blood Pressure and Regional Blood Flow in Conscious Rats

PubMed Central

Takemoto, Yumi

2012-01-01

Functional roles of amino acids have increasingly become the focus of research. This paper summarizes amino acids that influence cardiovascular system via the brain of conscious rats. This paper firstly describes why amino acids are selected and outlines how the brain regulates blood pressure and regional blood flow. This section includes a concise history of amino acid neurotransmitters in cardiovascular research and summarizes brain areas where chemical stimulations produce blood pressure changes mainly in anesthetized animals. This is followed by comments about findings regarding several newly examined amino acids with intracisternal stimulation in conscious rats that produce changes in blood pressure. The same pressor or depressor response to central amino acid stimulations can be produced by distinct mechanisms at central and peripheral levels, which will be briefly explained. Thereafter, cardiovascular actions of some of amino acids at the mechanism level will be discussed based upon findings of pharmacological and regional blood flow measurements. Several examined amino acids in addition to the established neurotransmitter amino acids appear to differentially activate brain structures to produce changes in blood pressure and regional blood flows. They may have physiological roles in the healthy brain, but pathological roles in the brain with cerebral vascular diseases such as stroke where the blood-brain barrier is broken. PMID:22690328

Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach

PubMed Central

Karamintziou, Sofia D.; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G.; Tagaris, George A.; Sakas, Damianos E.; Polychronaki, Georgia E.; Tsirogiannis, George L.; David, Olivier; Nikita, Konstantina S.

2017-01-01

Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson’s disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications. PMID:28222198

A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson's Disease.

PubMed

Camara, Carmen; Warwick, Kevin; Bruña, Ricardo; Aziz, Tipu; del Pozo, Francisco; Maestú, Fernando

2015-11-01

Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7% in 70% of the patients.

Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

PubMed Central

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

Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

PubMed

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.

The Social Context of "Do-It-Yourself" Brain Stimulation: Neurohackers, Biohackers, and Lifehackers.

PubMed

Wexler, Anna

2017-01-01

The "do-it-yourself" (DIY) brain stimulation movement began in earnest in late 2011, when lay individuals began building stimulation devices and applying low levels of electricity to their heads for self-improvement purposes. To date, scholarship on the home use of brain stimulation has focused on characterizing the practices of users via quantitative and qualitative studies, and on analyzing related ethical and regulatory issues. In this perspective piece, however, I take the opposite approach: rather than viewing the home use of brain stimulation on its own, I argue that it must be understood within the context of other DIY and citizen science movements. Seen in this light, the home use of brain stimulation is only a small part of the "neurohacking" movement, which is comprised of individuals attempting to optimize their brains to achieve enhanced performance. Neurohacking itself is an offshoot of the "life hacking" (or "quantified self") movement, in which individuals self-track minute aspects of their daily lives in order to enhance productivity or performance. Additionally, the home or DIY use of brain stimulation is in many ways parallel to the DIY Biology (or "biohacking") movement, which seeks to democratize tools of scientific experimentation. Here, I describe the place of the home use of brain stimulation with regard to neurohackers, lifehackers, and biohackers, and suggest that a policy approach for the home use of brain stimulation should have an appreciation both of individual motivations as well as the broader social context of the movement itself.

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

PubMed Central

Fox, Michael D.; Buckner, Randy L.; Liu, Hesheng; Chakravarty, M. Mallar; Lozano, Andres M.; Pascual-Leone, Alvaro

2014-01-01

Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

Real-time visualization of magnetic flux densities for transcranial magnetic stimulation on commodity and fully immersive VR systems

NASA Astrophysics Data System (ADS)

Kalivarapu, Vijay K.; Serrate, Ciro; Hadimani, Ravi L.

2017-05-01

Transcranial Magnetic Stimulation (TMS) is a non-invasive procedure that uses time varying short pulses of magnetic fields to stimulate nerve cells in the brain. In this method, a magnetic field generator ("TMS coil") produces small electric fields in the region of the brain via electromagnetic induction. This technique can be used to excite or inhibit firing of neurons, which can then be used for treatment of various neurological disorders such as Parkinson's disease, stroke, migraine, and depression. It is however challenging to focus the induced electric field from TMS coils to smaller regions of the brain. Since electric and magnetic fields are governed by laws of electromagnetism, it is possible to numerically simulate and visualize these fields to accurately determine the site of maximum stimulation and also to develop TMS coils that can focus the fields on the targeted regions. However, current software to compute and visualize these fields are not real-time and can work for only one position/orientation of TMS coil, severely limiting their usage. This paper describes the development of an application that computes magnetic flux densities (h-fields) and visualizes their distribution for different TMS coil position/orientations in real-time using GPU shaders. The application is developed for desktop, commodity VR (HTC Vive), and fully immersive VR CAVETM systems, for use by researchers, scientists, and medical professionals to quickly and effectively view the distribution of h-fields from MRI brain scans.

Engineering the next generation of clinical deep brain stimulation technology.

PubMed

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

2015-01-01

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

Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials.

PubMed

Houston, Brady; Blumenfeld, Zack; Quinn, Emma; Bronte-Stewart, Helen; Chizeck, Howard

2015-01-01

Current deep brain stimulation paradigms deliver continuous stimulation to deep brain structures to ameliorate the symptoms of Parkinson's disease. This continuous stimulation has undesirable side effects and decreases the lifespan of the unit's battery, necessitating earlier replacement. A closed-loop deep brain stimulator that uses brain signals to determine when to deliver stimulation based on the occurrence of symptoms could potentially address these drawbacks of current technology. Attempts to detect Parkinsonian tremor using brain signals recorded during the implantation procedure have been successful. However, the ability of these methods to accurately detect tremor over extended periods of time is unknown. Here we use local field potentials recorded during a deep brain stimulation clinical follow-up visit 1 month after initial programming to build a tremor detection algorithm and use this algorithm to detect tremor in subsequent visits up to 8 months later. Using this method, we detected the occurrence of tremor with accuracies between 68-93%. These results demonstrate the potential of tremor detection methods for efficacious closed-loop deep brain stimulation over extended periods of time.

Contributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits.

PubMed

Brocka, Marta; Helbing, Cornelia; Vincenz, Daniel; Scherf, Thomas; Montag, Dirk; Goldschmidt, Jürgen; Angenstein, Frank; Lippert, Michael

2018-04-30

Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful interpretation of reward-related human fMRI data. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

An adaptive brain actuated system for augmenting rehabilitation

PubMed Central

Roset, Scott A.; Gant, Katie; Prasad, Abhishek; Sanchez, Justin C.

2014-01-01

For people living with paralysis, restoration of hand function remains the top priority because it leads to independence and improvement in quality of life. In approaches to restore hand and arm function, a goal is to better engage voluntary control and counteract maladaptive brain reorganization that results from non-use. Standard rehabilitation augmented with developments from the study of brain-computer interfaces could provide a combined therapy approach for motor cortex rehabilitation and to alleviate motor impairments. In this paper, an adaptive brain-computer interface system intended for application to control a functional electrical stimulation (FES) device is developed as an experimental test bed for augmenting rehabilitation with a brain-computer interface. The system's performance is improved throughout rehabilitation by passive user feedback and reinforcement learning. By continuously adapting to the user's brain activity, similar adaptive systems could be used to support clinical brain-computer interface neurorehabilitation over multiple days. PMID:25565945

Addictive drugs and brain stimulation reward.

PubMed

Wise, R A

1996-01-01

Direct electrical or chemical stimulation of specific brain regions can establish response habits similar to those established by natural rewards such as food or sexual contact. Cocaine, mu and delta opiates, nicotine, phencyclidine, and cannabis each have actions that summate with rewarding electrical stimulation of the medial forebrain bundle (MFB). The reward-potentiating effects of amphetamine and opiates are associated with central sites of action where these drugs also have their direct rewarding effects, suggesting common mechanisms for drug reward per se and for drug potentiation of brain stimulation reward. The central sites at which these and perhaps other drugs of abuse potentiate brain stimulation reward and are rewarding in their own right are consistent with the hypothesis that the laboratory reward of brain stimulation and the pharmacological rewards of addictive drugs are habit forming because they act in the brain circuits that subserve more natural and biologically significant rewards.

Economic substitutability of electrical brain stimulation, food, and water.

PubMed Central

Green, L; Rachlin, H

1991-01-01

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other. PMID:2037823

Combined effects of cerebellar transcranial direct current stimulation and transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke: A pilot, single blind, randomized controlled trial.

PubMed

Picelli, Alessandro; Chemello, Elena; Castellazzi, Paola; Filippetti, Mirko; Brugnera, Annalisa; Gandolfi, Marialuisa; Waldner, Andreas; Saltuari, Leopold; Smania, Nicola

2018-01-01

Preliminary evidence showed additional effects of anodal transcranial direct current stimulation over the damaged cerebral hemisphere combined with cathodal transcutaneous spinal direct current stimulation during robot-assisted gait training in chronic stroke patients. This is consistent with the neural organization of locomotion involving cortical and spinal control. The cerebellum is crucial for locomotor control, in particular for avoidance of obstacles, and adaptation to novel conditions during walking. Despite its key role in gait control, to date the effects of transcranial direct current stimulation of the cerebellum have not been investigated on brain stroke patients treated with robot-assisted gait training. To evaluate the effects of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke. After balanced randomization, 20 chronic stroke patients received ten, 20-minute robot-assisted gait training sessions (five days a week, for two consecutive weeks) combined with central nervous system stimulation. Group 1 underwent on-line cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation. Group 2 received on-line anodal transcranial direct current stimulation over the damaged cerebral hemisphere + cathodal transcutaneous spinal direct current stimulation. The primary outcome was the 6-minute walk test performed before, after, and at follow-up at 2 and 4 weeks post-treatment. The significant differences in the 6-minute walk test noted between groups at the first post-treatment evaluation (p = 0.041) were not maintained at either the 2-week (P = 0.650) or the 4-week (P = 0.545) follow-up evaluations. Our preliminary findings support the hypothesis that cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere in combination with cathodal transcutaneous spinal direct current stimulation might be useful to boost the effects of robot-assisted gait training in chronic brain stroke patients with walking impairment.

The science of neural interface systems.

PubMed

Hatsopoulos, Nicholas G; Donoghue, John P

2009-01-01

The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.

Exaggerated Increases in Microglia Proliferation, Brain Inflammatory Response and Sickness Behaviour upon Lipopolysaccharide Stimulation in Non-Obese Diabetic Mice.

PubMed

McGuiness, Barry; Gibney, Sinead M; Beumer, Wouter; Versnel, Marjan A; Sillaber, Inge; Harkin, Andrew; Drexhage, Hemmo A

2016-01-01

The non-obese diabetic (NOD) mouse, an established model for autoimmune diabetes, shows an exaggerated reaction of pancreas macrophages to inflammatory stimuli. NOD mice also display anxiety when immune-stimulated. Chronic mild brain inflammation and a pro-inflammatory microglial activation is critical in psychiatric behaviour. To explore brain/microglial activation and behaviour in NOD mice at steady state and after systemic lipopolysaccharide (LPS) injection. Affymetrix analysis on purified microglia of pre-diabetic NOD mice (8-10 weeks) and control mice (C57BL/6 and CD1 mice, the parental non-autoimmune strain) at steady state and after systemic LPS (100 μg/kg) administration. Quantitative PCR was performed on the hypothalamus for immune activation markers (IL-1β, IFNγ and TNFα) and growth factors (BDNF and PDGF). Behavioural profiling of NOD, CD1, BALB/c and C57BL/6 mice at steady state was conducted and sickness behaviour/anxiety in NOD and CD1 mice was monitored before and after LPS injection. Genome analysis revealed cell cycle/cell death and survival aberrancies of NOD microglia, substantiated as higher proliferation on BrdU staining. Inflammation signs were absent. NOD mice had a hyper-reactive response to novel environments with some signs of anxiety. LPS injection induced a higher expression of microglial activation markers, a higher brain pro-inflammatory set point (IFNγ, IDO) and a reduced expression of BDNF and PDGF after immune stimulation in NOD mice. NOD mice displayed exaggerated and prolonged sickness behaviour after LPS administration. After stimulation with LPS, NOD mice display an increased microglial proliferation and an exaggerated inflammatory brain response with reduced BDNF and PDGF expression and increased sickness behaviour as compared to controls. © 2016 S. Karger AG, Basel.

Differential Modulation of Excitatory and Inhibitory Neurons during Periodic Stimulation

PubMed Central

Mahmud, Mufti; Vassanelli, Stefano

2016-01-01

Non-invasive transcranial neuronal stimulation, in addition to deep brain stimulation, is seen as a promising therapeutic and diagnostic approach for an increasing number of neurological diseases such as epilepsy, cluster headaches, depression, specific type of blindness, and other central nervous system disfunctions. Improving its effectiveness and widening its range of use may strongly rely on development of proper stimulation protocols that are tailored to specific brain circuits and that are based on a deep knowledge of different neuron types response to stimulation. To this aim, we have performed a simulation study on the behavior of excitatory and inhibitory neurons subject to sinusoidal stimulation. Due to the intrinsic difference in membrane conductance properties of excitatory and inhibitory neurons, we show that their firing is differentially modulated by the wave parameters. We analyzed the behavior of the two neuronal types for a broad range of stimulus frequency and amplitude and demonstrated that, within a small-world network prototype, parameters tuning allow for a selective enhancement or suppression of the excitation/inhibition ratio. PMID:26941602

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

PubMed Central

Nowak, Karl; Mix, Eilhard; Gimsa, Jan; Strauss, Ulf; Sriperumbudur, Kiran Kumar; Benecke, Reiner; Gimsa, Ulrike

2011-01-01

Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation. PMID:21603182

The Social Context of “Do-It-Yourself” Brain Stimulation: Neurohackers, Biohackers, and Lifehackers

PubMed Central

Wexler, Anna

2017-01-01

The “do-it-yourself” (DIY) brain stimulation movement began in earnest in late 2011, when lay individuals began building stimulation devices and applying low levels of electricity to their heads for self-improvement purposes. To date, scholarship on the home use of brain stimulation has focused on characterizing the practices of users via quantitative and qualitative studies, and on analyzing related ethical and regulatory issues. In this perspective piece, however, I take the opposite approach: rather than viewing the home use of brain stimulation on its own, I argue that it must be understood within the context of other DIY and citizen science movements. Seen in this light, the home use of brain stimulation is only a small part of the “neurohacking” movement, which is comprised of individuals attempting to optimize their brains to achieve enhanced performance. Neurohacking itself is an offshoot of the “life hacking” (or “quantified self”) movement, in which individuals self-track minute aspects of their daily lives in order to enhance productivity or performance. Additionally, the home or DIY use of brain stimulation is in many ways parallel to the DIY Biology (or “biohacking”) movement, which seeks to democratize tools of scientific experimentation. Here, I describe the place of the home use of brain stimulation with regard to neurohackers, lifehackers, and biohackers, and suggest that a policy approach for the home use of brain stimulation should have an appreciation both of individual motivations as well as the broader social context of the movement itself. PMID:28539877

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

PubMed

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

2009-03-01

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

Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression.

PubMed

Stone, Eric A; Lehmann, Michael L; Lin, Yan; Quartermain, David

2007-08-15

A previous study showed that two mouse models of behavioral depression, immune system activation and depletion of brain monoamines, are accompanied by marked reductions in stimulated neural activity in brain regions involved in motivated behavior. The present study tested whether this effect is common to other depression models by examining the effects of repeated forced swimming, chronic subordination stress or acute intraventricular galanin injection - three additional models - on baseline or stimulated c-fos expression in several brain regions known to be involved in motor or motivational processes (secondary motor, M2, anterior piriform cortex, APIR, posterior cingulate gyrus, CG, nucleus accumbens, NAC). Each of the depression models was found to reduce the fos response stimulated by exposure to a novel cage or a swim stress in all four of these brain areas but not to affect the response of a stress-sensitive region (paraventricular hypothalamus, PVH) that was included for control purposes. Baseline fos expression in these structures was either unaffected or affected in an opposite direction to the stimulated response. Pretreatment with either desmethylimipramine (DMI) or tranylcypromine (tranyl) attenuated these changes. It is concluded that the pattern of a reduced neural function of CNS motor/motivational regions with an increased function of stress areas is common to 5 models of behavioral depression in the mouse and is a potential experimental analog of the neural activity changes occurring in the clinical condition.

Phase-Locked Loop for Precisely Timed Acoustic Stimulation during Sleep

PubMed Central

Santostasi, Giovanni; Malkani, Roneil; Riedner, Brady; Bellesi, Michele; Tononi, Giulio; Paller, Ken A.; Zee, Phyllis C.

2016-01-01

Background A Brain-Computer Interface could potentially enhance the various benefits of sleep. New Method We describe a strategy for enhancing slow-wave sleep (SWS) by stimulating the sleeping brain with periodic acoustic stimuli that produce resonance in the form of enhanced slow-wave activity in the electroencephalogram (EEG). The system delivers each acoustic stimulus at a particular phase of an electrophysiological rhythm using a Phase-Locked Loop (PLL). Results The PLL is computationally economical and well suited to follow and predict the temporal behavior of the EEG during slow-wave sleep. Comparison with Existing Methods Acoustic stimulation methods may be able to enhance SWS without the risks inherent in electrical stimulation or pharmacological methods. The PLL method differs from other acoustic stimulation methods that are based on detecting a single slow wave rather than modeling slow-wave activity over an extended period of time. Conclusions By providing real-time estimates of the phase of ongoing EEG oscillations, the PLL can rapidly adjust to physiological changes, thus opening up new possibilities to study brain dynamics during sleep. Future application of these methods hold promise for enhancing sleep quality and associated daytime behavior and improving physiologic function. PMID:26617321

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Selective increase of intention-based economic decisions by noninvasive brain stimulation to the dorsolateral prefrontal cortex.

PubMed

Nihonsugi, Tsuyoshi; Ihara, Aya; Haruno, Masahiko

2015-02-25

The intention behind another's action and the impact of the outcome are major determinants of human economic behavior. It is poorly understood, however, whether the two systems share a core neural computation. Here, we investigated whether the two systems are causally dissociable in the brain by integrating computational modeling, functional magnetic resonance imaging, and transcranial direct current stimulation experiments in a newly developed trust game task. We show not only that right dorsolateral prefrontal cortex (DLPFC) activity is correlated with intention-based economic decisions and that ventral striatum and amygdala activity are correlated with outcome-based decisions, but also that stimulation to the DLPFC selectively enhances intention-based decisions. These findings suggest that the right DLPFC is involved in the implementation of intention-based decisions in the processing of cooperative decisions. This causal dissociation of cortical and subcortical backgrounds may indicate evolutionary and developmental differences in the two decision systems. Copyright © 2015 the authors 0270-6474/15/53412-08$15.00/0.

Help With Depression

MedlinePlus

... techniques that focus on neuromodulation, which incorporates electrical, magnetic or other forms of energy to stimulate brain ... electroconvulsive therapy (ECT), vagus-nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and the experimental deep-brain stimulation ( ...

Recurrent, Delayed Hemorrhage Associated with Edoxaban after Deep Brain Stimulation Lead Placement

PubMed Central

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

[Complex stimulation of the locomotor and psycholingual develop- ment of children with perinatal lesions of the central nervous system].

PubMed

Skvortsov, I A; Khavkhun, L A; Ustinova, E V; I'lin, L B

1989-01-01

In 121 children with perinatal CNS damage a combined therapy was performed including, besides routine drug treatment, imitation stimulation of age-matched posture-++-tonic attitudes and motor skills, metameric reflexotherapy aimed at the CNS region lesioned, magnetotherapy, electric laser puncture targeted at correction of dysfunctioning brain structures. Treatment efficiency was controlled by the brain "development profile" derived from formalized neurological and neuropsychological investigations, and electroneuromyography. The efficiency of the therapy was considerably decreased by the 3rd semester of life.

Changing Brain Networks Through Non-invasive Neuromodulation

PubMed Central

To, Wing Ting; De Ridder, Dirk; Hart Jr., John; Vanneste, Sven

2018-01-01

Background/Objective: Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method: This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion: Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks. PMID:29706876

A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

PubMed

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.

Changing Brain Networks Through Non-invasive Neuromodulation.

PubMed

To, Wing Ting; De Ridder, Dirk; Hart, John; Vanneste, Sven

2018-01-01

Background/Objective : Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method : This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion : Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks.

Stimulating at the right time: phase-specific deep brain stimulation.

PubMed

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.

Magnetic fields in noninvasive brain stimulation.

PubMed

Vidal-Dourado, Marcos; Conforto, Adriana Bastos; Caboclo, Luis Otávio Sales Ferreira; Scaff, Milberto; Guilhoto, Laura Maria de Figueiredo Ferreira; Yacubian, Elza Márcia Targas

2014-04-01

The idea that magnetic fields could be used therapeutically arose 2000 years ago. These therapeutic possibilities were expanded after the discovery of electromagnetic induction by the Englishman Michael Faraday and the American Joseph Henry. In 1896, Arsène d'Arsonval reported his experience with noninvasive brain magnetic stimulation to the scientific French community. In the second half of the 20th century, changing magnetic fields emerged as a noninvasive tool to study the nervous system and to modulate neural function. In 1985, Barker, Jalinous, and Freeston presented transcranial magnetic stimulation, a relatively focal and painless technique. Transcranial magnetic stimulation has been proposed as a clinical neurophysiology tool and as a potential adjuvant treatment for psychiatric and neurologic conditions. This article aims to contextualize the progress of use of magnetic fields in the history of neuroscience and medical sciences, until 1985.

Brain plasticity and rehabilitation in stroke patients.

PubMed

Hara, Yukihiro

2015-01-01

In recent years, our understanding of motor learning, neuroplasticity and functional recovery after the occurrence of brain lesion has grown significantly. Novel findings in basic neuroscience have provided an impetus for research in motor rehabilitation. The brain reveals a spectrum of intrinsic capacities to react as a highly dynamic system which can change the properties of its neural circuits. This brain plasticity can lead to an extreme degree of spontaneous recovery and rehabilitative training may modify and boost the neuronal plasticity processes. Animal studies have extended these findings, providing insight into a broad range of underlying molecular and physiological events. Neuroimaging studies in human patients have provided observations at the systems level that often parallel findings in animals. In general, the best recoveries are associated with the greatest return toward the normal state of brain functional organization. Reorganization of surviving central nervous system elements supports behavioral recovery, for example, through changes in interhemispheric lateralization, activity of association cortices linked to injured zones, and organization of cortical representational maps. Evidence from animal models suggests that both motor learning and cortical stimulation alter intracortical inhibitory circuits and can facilitate long-term potentiation and cortical remodeling. Current researches on the physiology and use of cortical stimulation animal models and in humans with stroke related hemiplegia are reviewed in this article. In particular, electromyography (EMG) -controlled electrical muscle stimulation improves the motor function of the hemiparetic arm and hand. A multi-channel near-infrared spectroscopy (NIRS) studies in which the hemoglobin levels in the brain were non-invasively and dynamically measured during functional activity found that the cerebral blood flow in the injured sensory-motor cortex area is greatest during an EMG-controlled FES session. Only a few idea is, however, known for the optimal timing of the different processes and therapeutic interventions and for their interactions in detail. Finding optimal rehabilitation paradigms requires an optimal organization of the internal processes of neural plasticity and the therapeutic interventions in accordance with defined plastic time windows. In this review the mechanisms of spontaneous plasticity after stroke and experimental interventions to enhance plasticity are summarized, with an emphasis on functional electrical stimulation therapy.

New modalities of brain stimulation for stroke rehabilitation

PubMed Central

Lucas, T. H.; Carey, J. R.; Fetz, E. E.

2014-01-01

Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), trans-cranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation. PMID:23192336

Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state.

PubMed

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.

Cathodal Transcranial Direct Current Stimulation of the Right Wernicke's Area Improves Comprehension in Subacute Stroke Patients

ERIC Educational Resources Information Center

You, Dae Sang; Kim, Dae-Yul; Chun, Min Ho; Jung, Seung Eun; Park, Sung Jong

2011-01-01

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and…

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.

PubMed

Widge, Alik S; Malone, Donald A; Dougherty, Darin D

2018-01-01

Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

Brain-machine interfaces: electrophysiological challenges and limitations.

PubMed

Lega, Bradley C; Serruya, Mijail D; Zaghloul, Kareem A

2011-01-01

Brain-machine interfaces (BMI) seek to directly communicate with the human nervous system in order to diagnose and treat intrinsic neurological disorders. While the first generation of these devices has realized significant clinical successes, they often rely on gross electrical stimulation using empirically derived parameters through open-loop mechanisms of action that are not yet fully understood. Their limitations reflect the inherent challenge in developing the next generation of these devices. This review identifies lessons learned from the first generation of BMI devices (chiefly deep brain stimulation), identifying key problems for which the solutions will aid the development of the next generation of technologies. Our analysis examines four hypotheses for the mechanism by which brain stimulation alters surrounding neurophysiologic activity. We then focus on motor prosthetics, describing various approaches to overcoming the problems of decoding neural signals. We next turn to visual prosthetics, an area for which the challenges of signal coding to match neural architecture has been partially overcome. Finally, we close with a review of cortical stimulation, examining basic principles that will be incorporated into the design of future devices. Throughout the review, we relate the issues of each specific topic to the common thread of BMI research: translating new knowledge of network neuroscience into improved devices for neuromodulation.

Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

PubMed Central

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

Brain Stimulation and the Role of the Right Hemisphere in Aphasia Recovery.

PubMed

Turkeltaub, Peter E

2015-11-01

Aphasia is a common consequence of left hemisphere stroke and causes a disabling loss of language and communication ability. Current treatments for aphasia are inadequate, leaving a majority of aphasia sufferers with ongoing communication difficulties for the rest of their lives. In the past decade, two forms of noninvasive brain stimulation, repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have emerged as promising new treatments for aphasia. The most common brain stimulation protocols attempt to inhibit the intact right hemisphere based on the hypothesis that maladaptive activity in the right hemisphere limits language recovery in the left. There is now sufficient evidence to demonstrate that this approach, at least for repetitive transcranial magnetic stimulation, improves specific language abilities in aphasia. However, the biological mechanisms that produce these behavioral improvements remain poorly understood. Taken in the context of the larger neurobiological literature on aphasia recovery, the role of the right hemisphere in aphasia recovery remains unclear. Additional research is needed to understand biological mechanisms of recovery, in order to optimize brain stimulation treatments for aphasia. This article summarizes the current evidence on noninvasive brain stimulation methods for aphasia and the neuroscientific considerations surrounding treatments using right hemisphere inhibition. Suggestions are provided for further investigation and for clinicians whose patients ask about brain stimulation treatments for aphasia.

Prior stimulation of the endocannabinoid system prevents methamphetamine-induced dopaminergic neurotoxicity in the striatum through activation of CB2 receptors

PubMed Central

Nader, Joëlle; Rapino, Cinzia; Gennequin, Benjamin; Chavant, Francois; Francheteau, Maureen; Makriyannis, Alexandros; Duranti, Andrea; Maccarrone, Mauro; Solinas, Marcello; Thiriet, Nathalie

2016-01-01

Methamphetamine toxicity is associated with cell death and loss of dopamine neuron terminals in the striatum similar to what is found in some neurodegenerative diseases. Conversely, the endocannabinoid system (ECS) has been suggested to be neuroprotective in the brain, and new pharmacological tools have been developed to increase their endogenous tone. In this study, we evaluated whether ECS stimulation could reduce the neurotoxicity of high doses of methamphetamine on the dopamine system. We found that methamphetamine alters the levels of the major endocannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) in the striatum, suggesting that the ECS participates in the brain responses to methamphetamine. Δ9-tetrahydrocannabinol (THC), a cannabis-derived agonist of both CB1 and CB2 cannabinoid receptors, or inhibitors of the main enzymes responsible for the degradation of AEA and 2-AG (URB597 and JZL184, respectively), blunted the decrease in striatal protein levels of tyrosine hydroxylase induced by methamphetamine. In addition, antagonists of CB2, but not of CB1, blocked the preventive effects of URB597 and JZL184, suggesting that only the former receptor subtype is engaged in neuroprotection exerted by ECS stimulation. Finally, we found that methamphetamine increases striatal levels of the cytokine tumor necrosis factor alpha, an effect that was blocked by ECS stimulation. Altogether, our results indicate that stimulation of ECS prior to the administration of an overdose of meth-amphetamine considerably reduces the neurotoxicity of the drug through CB2 receptor activation and highlight a protective function for the ECS against the toxicity induced by drugs and other external insults to the brain. This article is part of the Special Issue entitled ‘CNS Stimulants’. PMID:24709540

State of the Art: Novel Applications for Cortical Stimulation.

PubMed

De Ridder, Dirk; Perera, Sanjaya; Vanneste, Sven

2017-04-01

Electrical stimulation via implanted electrodes that overlie the cortex of the brain is an upcoming neurosurgical technique that was hindered for a long time by insufficient knowledge of how the brain functions in a dynamic, physiological, and pathological way, as well as by technological limitations of the implantable stimulation devices. This paper provides an overview of cortex stimulation via implantable devices and introduces future possibilities to improve cortex stimulation. Cortex stimulation was initially used preoperatively as a technique to localize functions in the brain and only later evolved into a treatment technique. It was first used for pain, but more recently a multitude of pathologies are being targeted by cortex stimulation. These disorders are being treated by stimulating different cortical areas of the brain. Risks and complications are essentially similar to those related to deep brain stimulation and predominantly include haemorrhage, seizures, infection, and hardware failures. For cortex stimulation to fully mature, further technological development is required to predict its outcomes and improve stimulation designs. This includes the development of network science-based functional connectivity approaches, genetic analyses, development of navigated high definition transcranial alternating current stimulation, and development of pseudorandom stimulation designs for preventing habituation. In conclusion, cortex stimulation is a nascent but very promising approach to treating a variety of diseases, but requires further technological development for predicting outcomes, such as network science based functional connectivity approaches, genetic analyses, development of navigated transcranial electrical stimulation, and development of pseudorandom stimulation designs for preventing habituation. © 2017 International Neuromodulation Society.

Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

PubMed Central

Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

2015-01-01

Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

From miracle to reconciliation: a hermeneutic phenomenological study exploring the experience of living with Parkinson's disease following deep brain stimulation.

PubMed

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. It is of significant importance that health care professionals are aware of these dramatic changes in the patients' life and offer support during the adjustment process following Deep Brain Stimulation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD): A Review.

PubMed

Rubio, Belen; Boes, Aaron D; Laganiere, Simon; Rotenberg, Alexander; Jeurissen, Danique; Pascual-Leone, Alvaro

2016-05-01

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in the pediatric population. The clinical management of ADHD is currently limited by a lack of reliable diagnostic biomarkers and inadequate therapy for a minority of patients who do not respond to standard pharmacotherapy. There is optimism that noninvasive brain stimulation may help to address these limitations. Transcranial magnetic stimulation and transcranial direct current stimulation are 2 methods of noninvasive brain stimulation that modulate cortical excitability and brain network activity. Transcranial magnetic stimulation can be used diagnostically to probe cortical neurophysiology, whereas daily use of repetitive transcranial magnetic stimulation or transcranial direct current stimulation can induce long-lasting and potentially therapeutic changes in targeted networks. In this review, we highlight research showing the potential diagnostic and therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in pediatric ADHD. We also discuss the safety and ethics of using these tools in the pediatric population. © The Author(s) 2015.

Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

PubMed Central

Kent, Alexander R.; Grill, Warren M.

2012-01-01

Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

A Review of Transcranial Magnetic Stimulation and Multimodal Neuroimaging to Characterize Post-Stroke Neuroplasticity

PubMed Central

Auriat, Angela M.; Neva, Jason L.; Peters, Sue; Ferris, Jennifer K.; Boyd, Lara A.

2015-01-01

Following stroke, the brain undergoes various stages of recovery where the central nervous system can reorganize neural circuitry (neuroplasticity) both spontaneously and with the aid of behavioral rehabilitation and non-invasive brain stimulation. Multiple neuroimaging techniques can characterize common structural and functional stroke-related deficits, and importantly, help predict recovery of function. Diffusion tensor imaging (DTI) typically reveals increased overall diffusivity throughout the brain following stroke, and is capable of indexing the extent of white matter damage. Magnetic resonance spectroscopy (MRS) provides an index of metabolic changes in surviving neural tissue after stroke, serving as a marker of brain function. The neural correlates of altered brain activity after stroke have been demonstrated by abnormal activation of sensorimotor cortices during task performance, and at rest, using functional magnetic resonance imaging (fMRI). Electroencephalography (EEG) has been used to characterize motor dysfunction in terms of increased cortical amplitude in the sensorimotor regions when performing upper limb movement, indicating abnormally increased cognitive effort and planning in individuals with stroke. Transcranial magnetic stimulation (TMS) work reveals changes in ipsilesional and contralesional cortical excitability in the sensorimotor cortices. The severity of motor deficits indexed using TMS has been linked to the magnitude of activity imbalance between the sensorimotor cortices. In this paper, we will provide a narrative review of data from studies utilizing DTI, MRS, fMRI, EEG, and brain stimulation techniques focusing on TMS and its combination with uni- and multimodal neuroimaging methods to assess recovery after stroke. Approaches that delineate the best measures with which to predict or positively alter outcomes will be highlighted. PMID:26579069

Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of "Smart" Deep Brain Stimulation

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.

2016-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Carbon Nanofiber Nanoelectrodes for Neural Stimulation and Chemical Detection: The Era of Smart Deep Brain Stimulation

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.

2016-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable "smart" therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial.

PubMed

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 decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. clinicaltrials.gov Identifier: NCT00056563.

A Simple fMRI Compatible Robotic Stimulator to Study the Neural Mechanisms of Touch and Pain.

PubMed

Riillo, F; Bagnato, C; Allievi, A G; Takagi, A; Fabrizi, L; Saggio, G; Arichi, T; Burdet, E

2016-08-01

This paper presents a simple device for the investigation of the human somatosensory system with functional magnetic imaging (fMRI). PC-controlled pneumatic actuation is employed to produce innocuous or noxious mechanical stimulation of the skin. Stimulation patterns are synchronized with fMRI and other relevant physiological measurements like electroencephalographic activity and vital physiological parameters. The system allows adjustable regulation of stimulation parameters and provides consistent patterns of stimulation. A validation experiment demonstrates that the system safely and reliably identifies clusters of functional activity in brain regions involved in the processing of pain. This new device is inexpensive, portable, easy-to-assemble and customizable to suit different experimental requirements. It provides robust and consistent somatosensory stimulation, which is of crucial importance to investigating the mechanisms of pain and its strong connection with the sense of touch.

Rethinking the thinking cap

PubMed Central

Messing, Samuel; Chatterjee, Anjan

2011-01-01

Although a growing body of evidence suggests that noninvasive brain stimulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation have the capacity to enhance neural function in both brain-injured and neurally intact individuals, the implications of their potential use for cosmetic self-enhancement have not been fully explored. We review 3 areas in which noninvasive brain stimulation has the potential to enhance neurologic function: cognitive skills, mood, and social cognition. We then characterize the ethical problems that affect the practice of cosmetic neurology, including safety, character, justice, and autonomy, and discuss how these problems may apply to the use of noninvasive brain stimulation for self-enhancement. PMID:21220723

[STUDYING THE ROLE OF BRAIN MELANOCORTIN RECEPTORS IN THE SUPPRESSING OF FOOD INTAKE UNDER ETHER STRESS IN MICE].

PubMed

Bazhan, N M; Kulikova, E V; Makarova, E N; Yakovleva, T V; Kazantseva, A Yu

2015-12-01

Melanocortin (MC) system regulates food intake under the rest conditions. Stress inhibits food intake. It is not clear whether brain MC system is involved in stress-induced anorexia in mice. The aim of the work was to investigate the effect of pharmacological blockade and activation of brain MC receptors on food intake under stress. C57B1/6J male mice were subjected to ether stress (0.5 minute ether anesthesia) before the administration of saline solution or synthetic non-selective blocker (SHU9119) or agonist (Melanotan II) of MC receptors into the lateral brain ventricle. Food intake was pre-stimulated with 17 hours of fasting in all mice. Ether stress decreased food intake, increased the plasma corticosterone level and hypothalamic mRNA AgRP (natural MC receptor antagonist) level at 1 hour after the stress. Pharmacological blockade of the MC receptors weakened stress-induced anorexia and decreased mRNA AgRP level in the hypothalamus. Pharmacological stimulation of the MC receptors enhanced ether stress-induced anorexia and hypercortisolism. Thus, our data demonstrated that the central MC system was involved in the development of stress-induced anorexia in mice.

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.

Deep Brain Stimulation

PubMed Central

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

A tripolar current-steering stimulator ASIC for field shaping in deep brain stimulation.

PubMed

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.

Basic and functional effects of transcranial Electrical Stimulation (tES)-An introduction.

PubMed

Yavari, Fatemeh; Jamil, Asif; Mosayebi Samani, Mohsen; Vidor, Liliane Pinto; Nitsche, Michael A

2018-02-01

Non-invasive brain stimulation (NIBS) has been gaining increased popularity in human neuroscience research during the last years. Among the emerging NIBS tools is transcranial electrical stimulation (tES), whose main modalities are transcranial direct, and alternating current stimulation (tDCS, tACS). In tES, a small current (usually less than 3mA) is delivered through the scalp. Depending on its shape, density, and duration, the applied current induces acute or long-lasting effects on excitability and activity of cerebral regions, and brain networks. tES is increasingly applied in different domains to (a) explore human brain physiology with regard to plasticity, and brain oscillations, (b) explore the impact of brain physiology on cognitive processes, and (c) treat clinical symptoms in neurological and psychiatric diseases. In this review, we give a broad overview of the main mechanisms and applications of these brain stimulation tools. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain

PubMed Central

2016-01-01

Abstract When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation. PMID:27752540

Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

PubMed

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.

Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation

PubMed Central

Heinrichs, Jan-Hendrik

2017-01-01

According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section “Why Could There Be Ethical Parity between Neural Tissue and External Tools?” presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section “Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis” will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section “On the Ethical Relevance of Situated Cognition Theses” will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies. PMID:28443008

Against Strong Ethical Parity: Situated Cognition Theses and Transcranial Brain Stimulation.

PubMed

Heinrichs, Jan-Hendrik

2017-01-01

According to a prominent suggestion in the ethics of transcranial neurostimulation the effects of such devices can be treated as ethically on par with established, pre-neurotechnological alterations of the mind. This parity allegedly is supported by situated cognition theories showing how external devices can be part of a cognitive system. This article will evaluate this suggestion. It will reject the claim, that situated cognition theories support ethical parity. It will however point out another reason, why external carriers or modifications of the mental might come to be considered ethically on par with internal carriers. Section "Why Could There Be Ethical Parity between Neural Tissue and External Tools?" presents the ethical parity theses between external and internal carriers of the mind as well as neurotechnological alterations and established alterations. Section "Extended, Embodied, Embedded: Situated Cognition as a Relational Thesis" will elaborate the different situated cognition approaches and their relevance for ethics. It will evaluate, whether transcranial stimulation technologies are plausible candidates for situated cognition theses. Section "On the Ethical Relevance of Situated Cognition Theses" will discuss criteria for evaluating whether a cognitive tool is deeply embedded with a cognitive system and apply these criteria to transcranial brain stimulation technologies. Finally it will discuss the role diverse versions of situated cognition theory can play in the ethics of altering mental states, especially the ethics of transcranial brain stimulation technologies.

Combined brain Fe, Cu, Zn and neurometabolite analysis - a new methodology for unraveling the efficacy of transcranial direct current stimulation (tDCS) in appetite control.

PubMed

Ziomber, Agata; Surowka, Artur Dawid; Antkiewicz-Michaluk, Lucyna; Romanska, Irena; Wrobel, Pawel; Szczerbowska-Boruchowska, Magdalena

2018-03-01

Obesity is a chronic, multifactorial origin disease that has recently become one of the most frequent lifestyle disorders. Unfortunately, current obesity treatments seem to be ineffective. At present, transcranial direct current brain stimulation (tDCS) represents a promising novel treatment methodology that seems to be efficient, well-tolerated and safe for a patient. Unfortunately, the biochemical action of tDCS remains unknown, which prevents its widespread use in the clinical arena, although neurobiochemical changes in brain signaling and metal metabolism are frequently reported. Therefore, our research aimed at exploring the biochemical response to tDCS in situ, in the brain areas triggering feeding behavior in obese animals. The objective was to propose a novel neurochemical (serotoninergic and dopaminergic signaling) and trace metal analysis of Fe, Cu and Zn. In doing so, we used energy-dispersive X-ray fluorescence (EDXRF) and high-performance liquid chromatography (HPLC). Anodal-type stimulation (atDCS) of the right frontal cortex was utilized to down-regulate food intake and body weight gain in obese rats. EDXRF was coupled with the external standard method in order to quantify the chemical elements within appetite-triggering brain areas. Major dopamine metabolites were assessed in the brains, based on the HPLC assay utilizing the external standard assay. Our study confirms that elemental analysis by EDXRF and brain metabolite assay by HPLC can be considered as a useful tool for the in situ investigation of the interplay between neurochemical and Fe/Cu/Zn metabolism in the brain upon atDCS. With this methodology, an increase in both Cu and Zn in the satiety center of the stimulated group could be reported. In turn, the most significant neurochemical changes involved dopaminergic and serotoninergic signaling in the brain reward system.

Alpha-Band Rhythms in Visual Task Performance: Phase-Locking by Rhythmic Sensory Stimulation

PubMed Central

de Graaf, Tom A.; Gross, Joachim; Paterson, Gavin; Rusch, Tessa; Sack, Alexander T.; Thut, Gregor

2013-01-01

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8–12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles. PMID:23555873

Modulation of the Endocannabinoid System: Vulnerability Factor and New Treatment Target for Stimulant Addiction

PubMed Central

Olière, Stéphanie; Jolette-Riopel, Antoine; Potvin, Stéphane; Jutras-Aswad, Didier

2013-01-01

Cannabis is one of the most widely used illicit substance among users of stimulants such as cocaine and amphetamines. Interestingly, increasing recent evidence points toward the involvement of the endocannabinoid system (ECBS) in the neurobiological processes related to stimulant addiction. This article presents an up-to-date review with deep insights into the pivotal role of the ECBS in the neurobiology of stimulant addiction and the effects of its modulation on addictive behaviors. This article aims to: (1) review the role of cannabis use and ECBS modulation in the neurobiological substrates of psychostimulant addiction and (2) evaluate the potential of cannabinoid-based pharmacological strategies to treat stimulant addiction. A growing number of studies support a critical role of the ECBS and its modulation by synthetic or natural cannabinoids in various neurobiological and behavioral aspects of stimulants addiction. Thus, cannabinoids modulate brain reward systems closely involved in stimulants addiction, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for treating addiction across different classes of stimulants. PMID:24069004

Learning from the spinal cord: How the study of spinal cord plasticity informs our view of learning

PubMed Central

Grau, James W.

2013-01-01

The paper reviews research examining whether and how training can induce a lasting change in spinal cord function. A framework for the study of learning, and some essential issues in experimental design, are discussed. A core element involves delayed assessment under common conditions. Research has shown that brain systems can induce a lasting (memory-like) alteration in spinal function. Neurons within the lower (lumbosacral) spinal cord can also adapt when isolated from the brain by means of a thoracic transection. Using traditional learning paradigms, evidence suggests that spinal neurons support habituation and sensitization as well as Pavlovian and instrumental conditioning. At a neurobiological level, spinal systems support phenomena (e.g., long-term potentiation), and involve mechanisms (e.g., NMDA mediated plasticity, protein synthesis) implicated in brain-dependent learning and memory. Spinal learning also induces modulatory effects that alter the capacity for learning. Uncontrollable/unpredictable stimulation disables the capacity for instrumental learning and this effect has been linked to the cytokine tumor necrosis factor (TNF). Predictable/controllable stimulation enables learning and counters the adverse effects of uncontrollable simulation through a process that depends upon brain-derived neurotrophic factor (BDNF). Finally, uncontrollable, but not controllable, nociceptive stimulation impairs recovery after a contusion injury. A process-oriented approach (neurofunctionalism) is outlined that encourages a broader view of learning phenomena. PMID:23973905

Evaluation of drug effects on cerebral blood flow and glucose uptake in un-anesthetized and un-stimulated rats: application of free-moving apparatus enabling to keep rats free during PET/SPECT tracer injection and uptake.

PubMed

Sugita, Taku; Kondo, Yusuke; Ishino, Seigo; Mori, Ikuo; Horiguchi, Takashi; Ogawa, Mikako; Magata, Yasuhiro

2018-05-15

The purpose of this study is the development of novel fluorine-18-fluorodeoxyglucose (F-FDG)-PET and Tc-hexamethylpropylene amine oxime (HMPAO) SPECT methods with free-moving apparatus on conscious rats to investigate brain activity without the effects of anesthesia and tactual stimulation. We also assessed the sensitivity of the experimental system by an intervention study using fluoxetine as a reference drug. A catheter was inserted into the femoral vein and connected to a free-moving cannula system. After fluoxetine administration, the rats were given an injection of F-FDG or Tc-HMPAO via the intravenous cannula and released into a free-moving cage. After the tracer was trapped in the brain, the rats were anesthetized and scanned with PET or SPECT scanners. Then a volume of interest analysis and statistical parametric mapping were performed. We could inject the tracer without touching the rats, while keeping them conscious until the tracers were distributed and trapped in the brain using the developed system. The effects of fluoxetine on glucose uptake and cerebral blood flow were perceptively detected by volume of interest and statistical parametric mapping analysis. We successfully developed free-moving F-FDG-PET and Tc-HMPAO-SPECT imaging systems and detected detailed glucose uptake and cerebral blood flow changes in the conscious rat brain with fluoxetine administration. This system is expected to be useful to assess brain activity without the effects of anesthesia and tactual stimulation to evaluate drug effect or animal brain function.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Coupling BCI and cortical stimulation for brain-state-dependent stimulation: methods for spectral estimation in the presence of stimulation after-effects

PubMed Central

Walter, Armin; Murguialday, Ander R.; Rosenstiel, Wolfgang; Birbaumer, Niels; Bogdan, Martin

2012-01-01

Brain-state-dependent stimulation (BSDS) combines brain-computer interfaces (BCIs) and cortical stimulation into one paradigm that allows the online decoding for example of movement intention from brain signals while simultaneously applying stimulation. If the BCI decoding is performed by spectral features, stimulation after-effects such as artefacts and evoked activity present a challenge for a successful implementation of BSDS because they can impair the detection of targeted brain states. Therefore, efficient and robust methods are needed to minimize the influence of the stimulation-induced effects on spectral estimation without violating the real-time constraints of the BCI. In this work, we compared four methods for spectral estimation with autoregressive (AR) models in the presence of pulsed cortical stimulation. Using combined EEG-TMS (electroencephalography-transcranial magnetic stimulation) as well as combined electrocorticography (ECoG) and epidural electrical stimulation, three patients performed a motor task using a sensorimotor-rhythm BCI. Three stimulation paradigms were varied between sessions: (1) no stimulation, (2) single stimulation pulses applied independently (open-loop), or (3) coupled to the BCI output (closed-loop) such that stimulation was given only while an intention to move was detected using neural data. We found that removing the stimulation after-effects by linear interpolation can introduce a bias in the estimation of the spectral power of the sensorimotor rhythm, leading to an overestimation of decoding performance in the closed-loop setting. We propose the use of the Burg algorithm for segmented data to deal with stimulation after-effects. This work shows that the combination of BCIs controlled with spectral features and cortical stimulation in a closed-loop fashion is possible when the influence of stimulation after-effects on spectral estimation is minimized. PMID:23162436

Remote radio control of insect flight.

PubMed

Sato, Hirotaka; Berry, Christopher W; Peeri, Yoav; Baghoomian, Emen; Casey, Brendan E; Lavella, Gabriel; Vandenbrooks, John M; Harrison, Jon F; Maharbiz, Michel M

2009-01-01

We demonstrated the remote control of insects in free flight via an implantable radio-equipped miniature neural stimulating system. The pronotum mounted system consisted of neural stimulators, muscular stimulators, a radio transceiver-equipped microcontroller and a microbattery. Flight initiation, cessation and elevation control were accomplished through neural stimulus of the brain which elicited, suppressed or modulated wing oscillation. Turns were triggered through the direct muscular stimulus of either of the basalar muscles. We characterized the response times, success rates, and free-flight trajectories elicited by our neural control systems in remotely controlled beetles. We believe this type of technology will open the door to in-flight perturbation and recording of insect flight responses.

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.

PubMed

Kraus, Thomas; Kiess, Olga; Hösl, Katharina; Terekhin, Pavel; Kornhuber, Johannes; Forster, Clemens

2013-09-01

It has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation. Functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) effects in limbic and temporal structures have been detected in two independent studies. In the present study, we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal. It is hypothesized that different central nervous system (CNS) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents. 16 healthy subjects aged between 20 and 37 years were divided into two groups. 8 subjects were stimulated in the anterior wall, the other 8 persons received transcutaneous vagus nervous stimulation (tVNS) at the posterior side of their left outer auditory canal. For sham control, both groups were also stimulated in an alternating manner on their corresponding ear lobe, which is generally known to be free of cutaneous vagal innervation. Functional MR data from the cortex and brain stem level were collected and a group analysis was performed. In most cortical areas, BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal. The only exception was in the insular cortex, where both stimulation types evoked positive BOLD changes. Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus, posterior cingulate cortex and right thalamus (pulvinar) following anterior stimulation. In subcortical areas at brain stem level, a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal. The results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Women's clitoris, vagina and cervix mapped on the sensory cortex: fMRI evidence

PubMed Central

Komisaruk, Barry R.; Wise, Nan; Frangos, Eleni; Liu, Wen-Ching; Allen, Kachina; Brody, Stuart

2011-01-01

Introduction The projection of vagina, uterine cervix, and nipple to the sensory cortex in humans has not been reported. Aims To map the sensory cortical fields of the clitoris, vagina, cervix and nipple, toward an elucidation of the neural systems underlying sexual response. Methods Using functional Magnetic Resonance Imaging (fMRI) we mapped sensory cortical responses to clitoral, vaginal, cervical, and nipple self-stimulation. For points of reference on the homunculus, we also mapped responses to the thumb and great toe (hallux) stimulation. Main Outcome Measures fMRI of brain regions activated by the various sensory stimuli. Results Clitoral, vaginal, and cervical self-stimulation activate differentiable sensory cortical regions, all clustered in the medial cortex (medial paracentral lobule). Nipple self-stimulation activated the genital sensory cortex (as well as the thoracic) region of the homuncular map. Conclusion The genital sensory cortex, identified in the classical Penfield homunculus based on electrical stimulation of the brain only in men, was confirmed for the first time in the literature by the present study in women, applying clitoral, vaginal, and cervical self-stimulation, and observing their regional brain responses using fMRI. Vaginal, clitoral, and cervical regions of activation were differentiable, consistent with innervation by different afferent nerves and different behavioral correlates. Activation of the genital sensory cortex by nipple self-stimulation was unexpected, but suggests a neurological basis for women’s reports of its erotogenic quality. PMID:21797981

A pioneer work on electric brain stimulation in psychotic patients. Rudolph Gottfried Arndt and his 1870s studies.

PubMed

Steinberg, Holger

2013-07-01

Today's brain stimulation methods are commonly traced back historically to surgical brain operations. With this one-sided historical approach it is easy to overlook the fact that non-surgical electrical brain-stimulating applications preceded present-day therapies. The first study on transcranial electrical brain stimulation for the treatment of severe mental diseases in a larger group of patients was carried out in the 1870s. Between 1870 and 1878 German psychiatrist Rudolph Gottfried Arndt published the results of his studies in three reports. These are contextualized with contemporary developments of the time, focusing in particular on the (neuro-) sciences. As was common practice at the time, Arndt basically reported individual cases in which electricity was applied to treat severe psychoses with depressive symptoms or even catatonia, hypochondriac delusion and melancholia. Despite their lengthiness, there is frequently a lack of precise physical data on the application of psychological-psychopathological details. Only his 1878 report includes general rules for electrical brain stimulation. Despite their methodological shortcomings and lack of precise treatment data impeding exact understanding, Arndt's studies are pioneering works in the field of electric brain stimulation with psychoses and its positive impacts. Today's transcranial direct current stimulation, and partly vagus nerve stimulation, can be compared with Arndt's methods. Although Arndt's only tangible results were indications for the application of faradic electricity (for inactivity, stupor, weakness and manic depressions) and galvanic current (for affective disorders and psychoses), a historiography of present-day brain stimulation therapies should no longer neglect studies on electrotherapy published in German and international psychiatric and neurological journals and monographs in the 1870s and 1880s. Copyright © 2013 Elsevier Inc. All rights reserved.

The Experience of Soviet Medicine in the Great Patriotic War 1941-1945,

DTIC Science & Technology

1980-02-06

mainly during shock/counterblow of brain against the contradictory/opposite walls of skull. Subliminal stimulations cause system resFonse of IX-X nerve...the same effect was cbtained during the stimulation of external auditory passage and muccsa of ncse. Vith sharp pressure to the region of the inguinal...zone of stimulation are invclved the centers cf tespcral region in combination with vestibular, auditory or gustatory aura. At the same time the

Brain Activations for Vestibular Stimulation and Dual Tasking Change with Spaceflight

NASA Technical Reports Server (NTRS)

Yuan, Peng; Koppelmans, Vincent; Reuter-Lorenz, Patricia; De Dios, Yiri; Gadd, Nichole; Wood, Scott; Riascos, Roy; Kofman, Igor; Bloomberg, Jacob; Mulavara, Ajitkumar;

Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.

PubMed

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.

The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.

PubMed

Mücke, Doris; Hermes, Anne; Roettger, Timo B; Becker, Johannes; Niemann, Henrik; Dembek, Till A; Timmermann, Lars; Visser-Vandewalle, Veerle; Fink, Gereon R; Grice, Martine; Barbe, Michael T

2018-01-01

Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow) or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements). To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA) in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF) with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF), patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.

Addition of visual noise boosts evoked potential-based brain-computer interface.

PubMed

Xie, Jun; Xu, Guanghua; Wang, Jing; Zhang, Sicong; Zhang, Feng; Li, Yeping; Han, Chengcheng; Li, Lili

2014-05-14

Although noise has a proven beneficial role in brain functions, there have not been any attempts on the dedication of stochastic resonance effect in neural engineering applications, especially in researches of brain-computer interfaces (BCIs). In our study, a steady-state motion visual evoked potential (SSMVEP)-based BCI with periodic visual stimulation plus moderate spatiotemporal noise can achieve better offline and online performance due to enhancement of periodic components in brain responses, which was accompanied by suppression of high harmonics. Offline results behaved with a bell-shaped resonance-like functionality and 7-36% online performance improvements can be achieved when identical visual noise was adopted for different stimulation frequencies. Using neural encoding modeling, these phenomena can be explained as noise-induced input-output synchronization in human sensory systems which commonly possess a low-pass property. Our work demonstrated that noise could boost BCIs in addressing human needs.

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography

NASA Astrophysics Data System (ADS)

Tian, Fenghua; Kozel, F. Andrew; Yennu, Amarnath; Croarkin, Paul E.; McClintock, Shawn M.; Mapes, Kimberly S.; Husain, Mustafa M.; Liu, Hanli

2012-11-01

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

EDITORIAL: Focus on the neural interface Focus on the neural interface

NASA Astrophysics Data System (ADS)

Durand, Dominique M.

2009-10-01

The possibility of an effective connection between neural tissue and computers has inspired scientists and engineers to develop new ways of controlling and obtaining information from the nervous system. These applications range from `brain hacking' to neural control of artificial limbs with brain signals. Notwithstanding the significant advances in neural prosthetics in the last few decades and the success of some stimulation devices such as cochlear prosthesis, neurotechnology remains below its potential for restoring neural function in patients with nervous system disorders. One of the reasons for this limited impact can be found at the neural interface and close attention to the integration between electrodes and tissue should improve the possibility of successful outcomes. The neural interfaces research community consists of investigators working in areas such as deep brain stimulation, functional neuromuscular/electrical stimulation, auditory prostheses, cortical prostheses, neuromodulation, microelectrode array technology, brain-computer/machine interfaces. Following the success of previous neuroprostheses and neural interfaces workshops, funding (from NIH) was obtained to establish a biennial conference in the area of neural interfaces. The first Neural Interfaces Conference took place in Cleveland, OH in 2008 and several topics from this conference have been selected for publication in this special section of the Journal of Neural Engineering. Three `perspectives' review the areas of neural regeneration (Corredor and Goldberg), cochlear implants (O'Leary et al) and neural prostheses (Anderson). Seven articles focus on various aspects of neural interfacing. One of the most popular of these areas is the field of brain-computer interfaces. Fraser et al, report on a method to generate robust control with simple signal processing algorithms of signals obtained with electrodes implanted in the brain. One problem with implanted electrode arrays, however, is that they can fail to record reliably neural signals for long periods of time. McConnell et al show that by measuring the impedance of the tissue, one can evaluate the extent of the tissue response to the presence of the electrode. Another problem with the neural interface is the mismatch of the mechanical properties between electrode and tissue. Basinger et al use finite element modeling to analyze this mismatch in retinal prostheses and guide the design of new implantable devices. Electrical stimulation has been the method of choice to activate externally the nervous system. However, Zhang et al show that a novel dual hybrid device integrating electrical and optical stimulation can provide an effective interface for simultaneous recording and stimulation. By interfacing an EMG recording system and a movement detection system, Johnson and Fuglevand develop a model capable of predicting muscle activity during movement that could be important for the development of motor prostheses. Sensory restoration is another unsolved problem in neural prostheses. By developing a novel interface between the dorsal root ganglia and electrodes arrays, Gaunt et al show that it is possible to recruit afferent fibers for sensory substitution. Finally, by interfacing directly with muscles, Jung and colleagues show that stimulation of muscles involved in locomotion following spinal cord damage in rats can provide an effective treatment modality for incomplete spinal cord injury. This series of articles clearly shows that the interface is indeed one of the keys to successful therapeutic neural devices. The next Neural Interfaces Conference will take place in Los Angeles, CA in June 2010 and one can expect to see new developments in neural engineering obtained by focusing on the neural interface.

Simultaneous detection of P300 and steady-state visually evoked potentials for hybrid brain-computer interface.

PubMed

Combaz, Adrien; Van Hulle, Marc M

2015-01-01

We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI. We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline. Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

PubMed

Rossini, P M; Burke, D; Chen, R; Cohen, L G; Daskalakis, Z; Di Iorio, R; Di Lazzaro, V; Ferreri, F; Fitzgerald, P B; George, M S; Hallett, M; Lefaucheur, J P; Langguth, B; Matsumoto, H; Miniussi, C; Nitsche, M A; Pascual-Leone, A; Paulus, W; Rossi, S; Rothwell, J C; Siebner, H R; Ugawa, Y; Walsh, V; Ziemann, U

2015-06-01

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Music therapy in neurological rehabilitation settings.

PubMed

Galińska, Elżbieta

2015-01-01

The neurologic music therapy is a new scope of music therapy. Its techniques deal with dysfunctions resulting from diseases of the human nervous system. Music can be used as an alternative modality to access functions unavailable through non-musical stimulus. Processes in the brain activated by the influence of music can be generalized and transferred to non-musical functions. Therefore, in clinical practice, the translation of non-musical therapeutic exercises into analogous, isomorphic musical exercises is performed. They make use of the executive peculiarity of musical instruments and musical structures to prime, cue and coordinate movements. Among musical components, a repetitive rhythm plays a significant role. It regulates physiologic and behavioural functions through the mechanism of entrainment (synchronization of biological rhythms with musical rhythm based on acoustic resonance). It is especially relevant for patients with a deficient internal timing system in the brain. Additionally, regular rhythmic patterns facilitate memory encoding and decoding of non-musical information hence music is an efficient mnemonic tool. The music as a hierarchical, compound language of time, with its unique ability to access affective/motivational systems in the brain, provides time structures enhancing perception processes, mainly in the range of cognition, language and motor learning. It allows for emotional expression and improvement of the motivation for rehabilitation activities. The new technologies of rhythmic sensory stimulation (i.e. Binaural Beat Stimulation) or rhythmic music in combination with rhythmic light therapy appear. This multimodal forms of stimulation are used in the treatment of stroke, brain injury, dementia and other cognitive deficits. Clinical outcome studies provide evidence of the significant superiority of rehabilitation with music over the one without music.

Noninvasive transcranial focused ultrasonic-magnetic stimulation for modulating brain oscillatory activity

NASA Astrophysics Data System (ADS)

Yuan, Yi; Chen, Yudong; Li, Xiaoli

2016-02-01

A novel technique, transcranial focused ultrasonic-magnetic stimulation (tFUMS), has been developed for noninvasive brain modulation in vivo. tFUMS has a higher spatial resolution (<2 mm) and a higher penetration depth than other noninvasive neuromodulation methods. The in vivo animal experimental results show that tFUMS can not only increase the power of local field potentials and the firing rate of the neurons, but also enhance the effect of transcranial focused ultrasound stimulation on the neuromodulation. The results demonstrate that tFUMS can modulate brain oscillatory activities by stimulating brain tissues.

Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation.

PubMed

Fornai, F; Bassi, L; Gesi, M; Giorgi, F S; Guerrini, R; Bonaccorsi, I; Alessandrì, M G

2000-01-01

Previous studies have shown that physiological stimulation of brain activity increases anaerobic glucose consumption, both in humans and in experimental animals. To investigate this phenomenon further, we measured extracellular lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizures. Olfactory stimulation was carried out by using different odors (i.e. both conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; thymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or focally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol and cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures induced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracellular lactic acid. Increases in extracellular lactate occurring during olfactory stimulation with the sexual pheromone (three times the baseline levels) were non-significantly different from those occurring after systemic pilocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local application of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocampal lactate induced by short-lasting stimuli (olfactory stimulation or microinfusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) were reproducible after a short delay (1 h) and cumulated when applied sequentially. In contrast, limbic status epilepticus led to a long-lasting refractoriness to additional lactate-raising stimuli and there was no further increase in lactate levels when the olfactory stimulation was produced during status epilepticus. Increases in lactic acid following olfactory stimulation occurred with site specificity in the rhinencephalon (hippocampus, piriform and entorhinal cortex) but not in the dorsal striatum. Site specificity crucially relied on the quality of the stimulus. For instance, other natural stimuli (i.e. tail pinch) produced a similar increase in extracellular lactate in all brain areas under investigation. The major conclusion of this work is that the presentation of an odor known to be a rat pheromone results in lactate production as great as that induced by the systemic convulsant pylocarpine (maximum: 2.286+/-0.195 mM and 1.803+/-0.108 mM, respectively). This supports the notion that the great magnitude of lactate production known to accompany seizures can result from the intensified neural activity per se ("aerobic gycolysis"), not merely from local anoxia or other pathological changes.

Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

PubMed

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 possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

A wirelessly controlled implantable LED system for deep brain optogenetic stimulation

PubMed Central

Rossi, Mark A.; Go, Vinson; Murphy, Tracy; Fu, Quanhai; Morizio, James; Yin, Henry H.

2015-01-01

In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially useful in studying the behavior of awake behaving animals. Conventional optogenetics, however, requires the use of lasers and optic fibers, which can place considerable restrictions on behavior. Here we combined a wirelessly controlled interface and small implantable light-emitting diode (LED) that allows flexible and precise placement of light source to illuminate any brain area. We tested this wireless LED system in vivo, in transgenic mice expressing channelrhodopsin-2 in striatonigral neurons expressing D1-like dopamine receptors. In all mice tested, we were able to elicit movements reliably. The frequency of twitches induced by high power stimulation is proportional to the frequency of stimulation. At lower power, contraversive turning was observed. Moreover, the implanted LED remains effective over 50 days after surgery, demonstrating the long-term stability of the light source. Our results show that the wireless LED system can be used to manipulate neural activity chronically in behaving mice without impeding natural movements. PMID:25713516

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

PubMed Central

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

Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

NASA Astrophysics Data System (ADS)

Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

1998-12-01

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

75 FR 51467 - ASK (Assess Specific Kinds of CHILDREN Challenges for Neurologic Devices) Study Children Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

..., including cochlear implants, deep brain stimulators, hydrocephalus shunts, spinal cord stimulators, and... pediatric populations, including cochlear implants, deep brain stimulators, hydrocephalus shunts, spinal...

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

PubMed Central

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

Dual roles of dopamine in food- and drug-seeking: the drive-reward paradox

PubMed Central

Wise, Roy A.

2012-01-01

The question of whether (or to what degree) obesity reflects addiction to high energy foods often narrows to the question of whether the overeating of these foods causes the same long-term neuroadaptations as are identified with the late stages of addiction. Of equal or perhaps greater interest is the question of whether common brain mechanisms mediate the acquisition and development of eating and drug-taking habits. The earliest evidence on this question is rooted in early studies of brain stimulation reward. Lateral hypothalamic electrical stimulation can be reinforcing in some conditions and can motivate feeding in others. That stimulation of the same brain region should be both reinforcing and drive-inducing is paradoxical; why should an animal work to induce a drive-like state such as hunger? This is known as the “drive-reward paradox.” Insights into the substrates of the drive-reward paradox suggest an answer to the controversial question of whether the dopamine system—a system “downstream” from the stimulated fibers of the lateral hypothalamus—is more critically involved in “wanting” or in “liking” of various rewards including food and addictive drugs. That the same brain circuitry is implicated in the motivation for and the reinforcement by both food and addictive drugs extends the argument for a common mechanism underlying compulsive overeating and compulsive drug-taking. PMID:23044182

From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia.

PubMed

Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

2012-04-01

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues. Copyright © 2010 Wiley Periodicals, Inc.

[Twiddler's syndrome in a patient with obsessive-compulsive disorder treated with deep brain stimulation].

PubMed

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.

Optically based quantification of absolute cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution in rodents

NASA Astrophysics Data System (ADS)

Yaseen, Mohammad A.; Srinivasan, Vivek J.; Sakadžić, Sava; Vinogradov, Sergei A.; Boas, David A.

2010-02-01

Measuring oxygen delivery in brain tissue is important for identifying the pathophysiological changes associated with brain injury and various diseases such as cancer, stroke, and Alzheimer's disease. We have developed a multi-modal imaging system for minimally invasive measurement of cerebral oxygenation and blood flow in small animals with high spatial resolution. The system allows for simultaneous measurement of blood flow using Fourier-domain optical coherence tomography, and oxygen partial pressure (pO2) using either confocal or multiphoton phosphorescence lifetime imaging with exogenous porphyrin-based dyes sensitive to dissolved oxygen. Here we present the changes in pO2 and blood flow in superficial cortical vessels of Sprague Dawley rats in response to conditions such as hypoxia, hyperoxia, and functional stimulation. pO2 measurements display considerable heterogeneity over distances that cannot be resolved with more widely used oxygen-monitoring techniques such as BOLD-fMRI. Large increases in blood flow are observed in response to functional stimulation and hypoxia. Our system allows for quantification of cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution, providing a better understanding of metabolic dynamics during functional stimulation and under various neuropathologies. Ultimately, better insight into the underlying mechanisms of neuropathologies will facilitate the development of improved therapeutic strategies to minimize damage to brain tissue.

Deep Brain Stimulation Frequency—A Divining Rod for New and Novel Concepts of Nervous System Function and Therapy

PubMed Central

Montgomery, Erwin B.; He, Huang

2016-01-01

The efficacy of Deep Brain Stimulation (DBS) for an expanding array of neurological and psychiatric disorders demonstrates directly that DBS affects the basic electroneurophysiological mechanisms of the brain. The increasing array of active electrode configurations, stimulation currents, pulse widths, frequencies, and pulse patterns provides valuable tools to probe electroneurophysiological mechanisms. The extension of basic electroneurophysiological and anatomical concepts using sophisticated computational modeling and simulation has provided relatively straightforward explanations of all the DBS parameters except frequency. This article summarizes current thought about frequency and relevant observations. Current methodological and conceptual errors are critically examined in the hope that future work will not replicate these errors. One possible alternative theory is presented to provide a contrast to many current theories. DBS, conceptually, is a noisy discrete oscillator interacting with the basal ganglia–thalamic–cortical system of multiple re-entrant, discrete oscillators. Implications for positive and negative resonance, stochastic resonance and coherence, noisy synchronization, and holographic memory (related to movement generation) are presented. The time course of DBS neuronal responses demonstrates evolution of the DBS response consistent with the dynamics of re-entrant mechanisms. Finally, computational modeling demonstrates identical dynamics as seen by neuronal activities recorded from human and nonhuman primates, illustrating the differences of discrete from continuous harmonic oscillators and the power of conceptualizing the nervous system as composed on interacting discrete nonlinear oscillators. PMID:27548234

Neuronal histamine and the interplay of memory, reinforcement and emotions.

PubMed

Dere, E; Zlomuzica, A; De Souza Silva, M A; Ruocco, L A; Sadile, A G; Huston, J P

2010-12-31

The biogenic amine histamine is an important neurotransmitter-neuromodulator in the central nervous system that has been implicated in a variety of biological functions including thermo- and immunoregulation, food intake, seizures, arousal, anxiety, reward and memory. The review of the pertinent literature indicates that the majority of findings are compatible with the appraisal that the inhibition of histaminergic neurotransmission impairs learning and memory formation, decreases cortical activation and arousal, has a suppressive effect on behavioral measures of fear and anxiety, exponentiates the rewarding effects of drugs of abuse and intracranial brain stimulation. In contrast, the stimulation of histaminergic neurotransmission can ameliorate learning and memory impairments that are associated with various experimental deficit models and pathological conditions. Clinical investigations with patients suffering from neurodegenerative diseases such as Alzheimer's and Parkinson's disease demonstrate pathological alterations in the brain's histaminergic system, which, in some cases are correlated with the severity of cognitive deficits. The role of the brain's histamine system in episodic memory formation and the potential of histamine-related drugs to ameliorate cognitive deficits in early stages of neurodegenerative diseases are discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

PubMed

Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

2016-08-01

Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. Copyright © 2016 Elsevier B.V. All rights reserved.

Adaptive Plasticity in the Healthy Language Network: Implications for Language Recovery after Stroke

PubMed Central

2016-01-01

Across the last three decades, the application of noninvasive brain stimulation (NIBS) has substantially increased the current knowledge of the brain's potential to undergo rapid short-term reorganization on the systems level. A large number of studies applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in the healthy brain to probe the functional relevance and interaction of specific areas for different cognitive processes. NIBS is also increasingly being used to induce adaptive plasticity in motor and cognitive networks and shape cognitive functions. Recently, NIBS has been combined with electrophysiological techniques to modulate neural oscillations of specific cortical networks. In this review, we will discuss recent advances in the use of NIBS to modulate neural activity and effective connectivity in the healthy language network, with a special focus on the combination of NIBS and neuroimaging or electrophysiological approaches. Moreover, we outline how these results can be transferred to the lesioned brain to unravel the dynamics of reorganization processes in poststroke aphasia. We conclude with a critical discussion on the potential of NIBS to facilitate language recovery after stroke and propose a phase-specific model for the application of NIBS in language rehabilitation. PMID:27830094

Stimulating at the right time: phase-specific deep brain stimulation

PubMed Central

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

Therapeutic Efficacy of Neurostimulation for Depression: Techniques, Current Modalities, and Future Challenges.

PubMed

Akhtar, Hafsah; Bukhari, Faiza; Nazir, Misbah; Anwar, Muhammad Nabeel; Shahzad, Adeeb

2016-02-01

Depression is the most prevalent debilitating mental illness; it is characterized as a disorder of mood, cognitive function, and neurovegetative function. About one in ten individuals experience depression at some stage of their lives. Antidepressant drugs are used to reduce the symptoms but relapse occurs in ~20% of patients. However, alternate therapies like brain stimulation techniques have shown promising results in this regard. This review covers the brain stimulation techniques electroconvulsive therapy, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, which are used as alternatives to antidepressant drugs, and elucidates their research and clinical outcomes.

The treatment of Parkinson's disease with deep brain stimulation: current issues.

PubMed

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.

Deep brain stimulation for people with Alzheimer's disease: Anticipating potential effects on the tripartite self.

PubMed

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.

76 FR 48062 - Effective Date of Requirement for Premarket Approval for Cranial Electrotherapy Stimulator

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... devices include headaches following treatment with electrical stimulation. Potential risk of seizure--electrical stimulation of the brain may result in seizures, particularly in patients with a history of... effects from electrical stimulation of the brain--The physiological effects associated with electrical...

Communication calls produced by electrical stimulation of four structures in the guinea pig brain

PubMed Central

Green, David B.; Shackleton, Trevor M.; Grimsley, Jasmine M. S.; Zobay, Oliver; Palmer, Alan R.

2018-01-01

One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation. PMID:29584746

Communication calls produced by electrical stimulation of four structures in the guinea pig brain.

PubMed

Green, David B; Shackleton, Trevor M; Grimsley, Jasmine M S; Zobay, Oliver; Palmer, Alan R; Wallace, Mark N

2018-01-01

One of the main central processes affecting the cortical representation of conspecific vocalizations is the collateral output from the extended motor system for call generation. Before starting to study this interaction we sought to compare the characteristics of calls produced by stimulating four different parts of the brain in guinea pigs (Cavia porcellus). By using anaesthetised animals we were able to reposition electrodes without distressing the animals. Trains of 100 electrical pulses were used to stimulate the midbrain periaqueductal grey (PAG), hypothalamus, amygdala, and anterior cingulate cortex (ACC). Each structure produced a similar range of calls, but in significantly different proportions. Two of the spontaneous calls (chirrup and purr) were never produced by electrical stimulation and although we identified versions of chutter, durr and tooth chatter, they differed significantly from our natural call templates. However, we were routinely able to elicit seven other identifiable calls. All seven calls were produced both during the 1.6 s period of stimulation and subsequently in a period which could last for more than a minute. A single stimulation site could produce four or five different calls, but the amygdala was much less likely to produce a scream, whistle or rising whistle than any of the other structures. These three high-frequency calls were more likely to be produced by females than males. There were also differences in the timing of the call production with the amygdala primarily producing calls during the electrical stimulation and the hypothalamus mainly producing calls after the electrical stimulation. For all four structures a significantly higher stimulation current was required in males than females. We conclude that all four structures can be stimulated to produce fictive vocalizations that should be useful in studying the relationship between the vocal motor system and cortical sensory representation.

Brain computer interface learning for systems based on electrocorticography and intracortical microelectrode arrays.

PubMed

Hiremath, Shivayogi V; Chen, Weidong; Wang, Wei; Foldes, Stephen; Yang, Ying; Tyler-Kabara, Elizabeth C; Collinger, Jennifer L; Boninger, Michael L

2015-01-01

A brain-computer interface (BCI) system transforms neural activity into control signals for external devices in real time. A BCI user needs to learn to generate specific cortical activity patterns to control external devices effectively. We call this process BCI learning, and it often requires significant effort and time. Therefore, it is important to study this process and develop novel and efficient approaches to accelerate BCI learning. This article reviews major approaches that have been used for BCI learning, including computer-assisted learning, co-adaptive learning, operant conditioning, and sensory feedback. We focus on BCIs based on electrocorticography and intracortical microelectrode arrays for restoring motor function. This article also explores the possibility of brain modulation techniques in promoting BCI learning, such as electrical cortical stimulation, transcranial magnetic stimulation, and optogenetics. Furthermore, as proposed by recent BCI studies, we suggest that BCI learning is in many ways analogous to motor and cognitive skill learning, and therefore skill learning should be a useful metaphor to model BCI learning.

A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

PubMed

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.

Non-pharmacological biological treatment approaches to difficult-to-treat depression.

PubMed

Fitzgerald, Paul B

2013-09-16

There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.

Effect of anatomical variability in brain on transcranial magnetic stimulation treatment

NASA Astrophysics Data System (ADS)

Syeda, F.; Magsood, H.; Lee, E. G.; El-Gendy, A. A.; Jiles, D. C.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

Electrical Guidance of Human Stem Cells in the Rat Brain.

PubMed

Feng, Jun-Feng; Liu, Jing; Zhang, Lei; Jiang, Ji-Yao; Russell, Michael; Lyeth, Bruce G; Nolta, Jan A; Zhao, Min

2017-07-11

Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Mechanism of orientation of stimulating currents in magnetic brain stimulation (abstract)

NASA Astrophysics Data System (ADS)

Ueno, S.; Matsuda, T.

1991-04-01

We made a functional map of the human motor cortex related to the hand and foot areas by stimulating the human brain with a focused magnetic pulse. We observed that each functional area in the cortex has an optimum direction for which stimulating currents can produce neural excitation. The present report focuses on the mechanism which is responsible for producing this anisotropic response to brain stimulation. We first obtained a functional map of the brain related to the left ADM (abductor digiti minimi muscles). When the stimulating currents were aligned in the direction from the left to the right hemisphere, clear EMG (electromyographic) responses were obtained only from the left ADM to magnetic stimulation of both hemisphere. When the stimulating currents were aligned in the direction from the right to the left hemisphere, clear EMG signals were obtained only from the right ADM to magnetic stimulation of both hemisphere. The functional maps of the brain were sensitive to changes in the direction of the stimulating currents. To explain the phenomena obtained in the experiments, we developed a model of neural excitation elicited by magnetic stimulation. When eddy currents which are induced by pulsed magnetic fields flow in the direction from soma to the distal part of neural fiber, depolarized area in the distal part are excited, and the membrane excitation propagates along the nerve fiber. In contrast, when the induced currents flow in the direction from the distal part to soma, hyperpolarized parts block or inhibit neural excitation even if the depolarized parts near the soma can be excited. The model explains our observation that the orientation of the induced current vectors reflect both the functional and anatomical organization of the neural fibers in the brain.

Brain stimulation in posttraumatic stress disorder

PubMed Central

Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A.B.; Mindes, Janet; A.Golier, Julia; Yehuda, Rachel

2011-01-01

Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. PMID:22893803

Emotional sounds and the brain: the neuro-affective foundations of musical appreciation.

PubMed

Panksepp, Jaak; Bernatzky, Günther

2002-11-01

This article summarizes the potential role of evolved brain emotional systems in the mediation of music appreciation. A variety of examples of how music may promote behavioral change are summarized, including effects on memory, mood, brain activity as well as autonomic responses such as the experience of 'chills'. Studies on animals (e.g. young chicks) indicate that musical stimulation have measurable effects on their behaviors and brain chemistries, especially increased brain norepinephrine (NE) turnover. The evolutionary sources of musical sensitivity are discussed, as well as the potential medical-therapeutic implications of this knowledge.

Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise.

PubMed

Okano, Alexandre Hideki; Fontes, Eduardo Bodnariuc; Montenegro, Rafael Ayres; Farinatti, Paulo de Tarso Veras; Cyrino, Edilson Serpeloni; Li, Li Min; Bikson, Marom; Noakes, Timothy David

2015-09-01

The temporal and insular cortex (TC, IC) have been associated with autonomic nervous system (ANS) control and the awareness of emotional feelings from the body. Evidence shows that the ANS and rating of perceived exertion (RPE) regulate exercise performance. Non-invasive brain stimulation can modulate the cortical area directly beneath the electrode related to ANS and RPE, but it could also affect subcortical areas by connection within the cortico-cortical neural networks. This study evaluated the effects of transcranial direct current stimulation (tDCS) over the TC on the ANS, RPE and performance during a maximal dynamic exercise. Ten trained cyclists participated in this study (33±9 years; 171.5±5.8 cm; 72.8±9.5 kg; 10-11 training years). After 20-min of receiving either anodal tDCS applied over the left TC (T3) or sham stimulation, subjects completed a maximal incremental cycling exercise test. RPE, heart rate (HR) and R-R intervals (as a measure of ANS function) were recorded continuously throughout the tests. Peak power output (PPO) was recorded at the end of the tests. With anodal tDCS, PPO improved by ~4% (anodal tDCS: 313.2±29.9 vs 301.0±19.8 watts: sham tDCS; p=0.043), parasympathetic vagal withdrawal was delayed (anodal tDCS: 147.5±53.3 vs 125.0±35.4 watts: sham tDCS; p=0.041) and HR was reduced at submaximal workloads. RPE also increased more slowly during exercise following anodal tDCS application, but maximal RPE and HR values were not affected by cortical stimulation. The findings suggest that non-invasive brain stimulation over the TC modulates the ANS activity and the sensory perception of effort and exercise performance, indicating that the brain plays a crucial role in the exercise performance regulation. 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.

Digestive System

MedlinePlus

... think about eating. In response to this sensory stimulation, the brain sends impulses through the nerves that ... it based on symptoms, medical history, and a physical exam. Problems With the Pancreas, Liver, and Gallbladder ...

Modulating Hippocampal Plasticity with In Vivo Brain Stimulation.

PubMed

Rohan, Joyce G; Carhuatanta, Kim A; McInturf, Shawn M; Miklasevich, Molly K; Jankord, Ryan

2015-09-16

Investigations into the use of transcranial direct current stimulation (tDCS) in relieving symptoms of neurological disorders and enhancing cognitive or motor performance have exhibited promising results. However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated that in vivo tDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings. Ex vivo preparations of hippocampal slices from rats that have been subjected to tDCS of 0.10 or 0.25 mA for 30 min followed by 30 min of recovery time displayed a robust twofold enhancement in long-term potentiation (LTP) induction accompanied by a 30% increase in paired-pulse facilitation (PPF). The magnitude of the LTP effect was greater with 0.25 mA compared with 0.10 mA stimulations, suggesting a dose-dependent relationship between tDCS intensity and its effect on synaptic plasticity. To test the persistence of these observed effects, animals were stimulated in vivo for 30 min at 0.25 mA and then allowed to return to their home cage for 24 h. Observation of the enhanced LTP induction, but not the enhanced PPF, continued 24 h after completion of 0.25 mA of tDCS. Addition of the NMDA blocker AP-5 abolished LTP in both control and stimulated rats but maintained the PPF enhancement in stimulated rats. The observation of enhanced LTP and PPF after tDCS demonstrates that non-invasive electrical stimulation is capable of modifying synaptic plasticity. Researchers have used brain stimulation such as transcranial direct current stimulation on human subjects to alleviate symptoms of neurological disorders and enhance their performance. Here, using rats, we have investigated the potential mechanisms of how in vivo brain stimulation can produce such effect. We recorded directly on viable brain slices from rats after brain stimulation to detect lasting changes in pattern of neuronal activity. Our results showed that 30 min of brain stimulation in rats induced a robust enhancement in synaptic plasticity, a neuronal process critical for learning and memory. Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects on cognition and performance. Copyright © 2015 the authors 0270-6474/15/3512824-09$15.00/0.

Modulating Hippocampal Plasticity with In Vivo Brain Stimulation

PubMed Central

Carhuatanta, Kim A.; McInturf, Shawn M.; Miklasevich, Molly K.; Jankord, Ryan

2015-01-01

Investigations into the use of transcranial direct current stimulation (tDCS) in relieving symptoms of neurological disorders and enhancing cognitive or motor performance have exhibited promising results. However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated that in vivo tDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings. Ex vivo preparations of hippocampal slices from rats that have been subjected to tDCS of 0.10 or 0.25 mA for 30 min followed by 30 min of recovery time displayed a robust twofold enhancement in long-term potentiation (LTP) induction accompanied by a 30% increase in paired-pulse facilitation (PPF). The magnitude of the LTP effect was greater with 0.25 mA compared with 0.10 mA stimulations, suggesting a dose-dependent relationship between tDCS intensity and its effect on synaptic plasticity. To test the persistence of these observed effects, animals were stimulated in vivo for 30 min at 0.25 mA and then allowed to return to their home cage for 24 h. Observation of the enhanced LTP induction, but not the enhanced PPF, continued 24 h after completion of 0.25 mA of tDCS. Addition of the NMDA blocker AP-5 abolished LTP in both control and stimulated rats but maintained the PPF enhancement in stimulated rats. The observation of enhanced LTP and PPF after tDCS demonstrates that non-invasive electrical stimulation is capable of modifying synaptic plasticity. SIGNIFICANCE STATEMENT Researchers have used brain stimulation such as transcranial direct current stimulation on human subjects to alleviate symptoms of neurological disorders and enhance their performance. Here, using rats, we have investigated the potential mechanisms of how in vivo brain stimulation can produce such effect. We recorded directly on viable brain slices from rats after brain stimulation to detect lasting changes in pattern of neuronal activity. Our results showed that 30 min of brain stimulation in rats induced a robust enhancement in synaptic plasticity, a neuronal process critical for learning and memory. Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects on cognition and performance. PMID:26377469

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

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.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

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

Influence of the implanted pulse generator as reference electrode in finite element model of monopolar deep brain stimulation.

PubMed

Walckiers, Grégoire; Fuchs, Benjamin; Thiran, Jean-Philippe; Mosig, Juan R; Pollo, Claudio

2010-01-30

Electrical deep brain stimulation (DBS) is an efficient method to treat movement disorders. Many models of DBS, based mostly on finite elements, have recently been proposed to better understand the interaction between the electrical stimulation and the brain tissues. In monopolar DBS, clinically widely used, the implanted pulse generator (IPG) is used as reference electrode (RE). In this paper, the influence of the RE model of monopolar DBS is investigated. For that purpose, a finite element model of the full electric loop including the head, the neck and the superior chest is used. Head, neck and superior chest are made of simple structures such as parallelepipeds and cylinders. The tissues surrounding the electrode are accurately modelled from data provided by the diffusion tensor magnetic resonance imaging (DT-MRI). Three different configurations of RE are compared with a commonly used model of reduced size. The electrical impedance seen by the DBS system and the potential distribution are computed for each model. Moreover, axons are modelled to compute the area of tissue activated by stimulation. Results show that these indicators are influenced by the surface and position of the RE. The use of a RE model corresponding to the implanted device rather than the usually simplified model leads to an increase of the system impedance (+48%) and a reduction of the area of activated tissue (-15%). (c) 2009 Elsevier B.V. All rights reserved.

Prolonged Repeated Acupuncture Stimulation Induces Habituation Effects in Pain-Related Brain Areas: An fMRI Study

PubMed Central

Li, Chuanfu; Yang, Jun; Park, Kyungmo; Wu, Hongli; Hu, Sheng; Zhang, Wei; Bu, Junjie; Xu, Chunsheng; Qiu, Bensheng; Zhang, Xiaochu

2014-01-01

Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia. PMID:24821143

Innovations in deep brain stimulation methodology.

PubMed

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.

Designing a deep brain stimulator to suppress pathological neuronal synchrony.

PubMed

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.

Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease

PubMed Central

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 observations raise the possibility that cortical connectivity with the subthalamic nucleus in the high and low beta bands may reflect coupling mediated predominantly by the hyperdirect and indirect pathways to subthalamic nucleus, respectively, and that subthalamic nucleus deep brain stimulation predominantly suppresses the former. Yet only the change in strength of local subthalamic nucleus oscillations correlates with the degree of improvement during deep brain stimulation, compatible with the current view that a strengthened hyperdirect pathway is a prerequisite for locally generated beta activity but that it is the severity of the latter that may determine or index motor impairment. PMID:27017189

A comparative study of approaches to compute the field distribution of deep brain stimulation in the Hemiparkinson rat model.

PubMed

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.

Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

PubMed

Censor, Nitzan; Dimyan, Michael A; Cohen, Leonardo G

2010-09-14

One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. Copyright © 2010 Elsevier Ltd. All rights reserved.

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.

PubMed

Kolodziej, Angela; Lippert, Michael; Angenstein, Frank; Neubert, Jenni; Pethe, Annette; Grosser, Oliver S; Amthauer, Holger; Schroeder, Ulrich H; Reymann, Klaus G; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

2014-12-01

Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Brain-machine interfaces in neurorehabilitation of stroke.

PubMed

Soekadar, Surjo R; Birbaumer, Niels; Slutzky, Marc W; Cohen, Leonardo G

2015-11-01

Stroke is among the leading causes of long-term disabilities leaving an increasing number of people with cognitive, affective and motor impairments depending on assistance in their daily life. While function after stroke can significantly improve in the first weeks and months, further recovery is often slow or non-existent in the more severe cases encompassing 30-50% of all stroke victims. The neurobiological mechanisms underlying recovery in those patients are incompletely understood. However, recent studies demonstrated the brain's remarkable capacity for functional and structural plasticity and recovery even in severe chronic stroke. As all established rehabilitation strategies require some remaining motor function, there is currently no standardized and accepted treatment for patients with complete chronic muscle paralysis. The development of brain-machine interfaces (BMIs) that translate brain activity into control signals of computers or external devices provides two new strategies to overcome stroke-related motor paralysis. First, BMIs can establish continuous high-dimensional brain-control of robotic devices or functional electric stimulation (FES) to assist in daily life activities (assistive BMI). Second, BMIs could facilitate neuroplasticity, thus enhancing motor learning and motor recovery (rehabilitative BMI). Advances in sensor technology, development of non-invasive and implantable wireless BMI-systems and their combination with brain stimulation, along with evidence for BMI systems' clinical efficacy suggest that BMI-related strategies will play an increasing role in neurorehabilitation of stroke. Copyright © 2014. Published by Elsevier Inc.

Steady-state visual evoked potential (SSVEP)-based communication: impact of harmonic frequency components

NASA Astrophysics Data System (ADS)

Müller-Putz, Gernot R.; Scherer, Reinhold; Brauneis, Christian; Pfurtscheller, Gert

2005-12-01

Brain-computer interfaces (BCIs) can be realized on the basis of steady-state evoked potentials (SSEPs). These types of brain signals resulting from repetitive stimulation have the same fundamental frequency as the stimulation but also include higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by incorporating visually evoked harmonic oscillations. The current study revealed that the use of three SSVEP harmonics yielded a significantly higher classification accuracy than was the case for one or two harmonics. During feedback experiments, the five subjects investigated reached a classification accuracy between 42.5% and 94.4%.

Steady-state visual evoked potential (SSVEP)-based communication: impact of harmonic frequency components.

PubMed

Müller-Putz, Gernot R; Scherer, Reinhold; Brauneis, Christian; Pfurtscheller, Gert

2005-12-01

Brain-computer interfaces (BCIs) can be realized on the basis of steady-state evoked potentials (SSEPs). These types of brain signals resulting from repetitive stimulation have the same fundamental frequency as the stimulation but also include higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by incorporating visually evoked harmonic oscillations. The current study revealed that the use of three SSVEP harmonics yielded a significantly higher classification accuracy than was the case for one or two harmonics. During feedback experiments, the five subjects investigated reached a classification accuracy between 42.5% and 94.4%.

Effects of Stimulation of the Subthalamic Nucleus on Naming and Reading Nouns and Verbs in Parkinson's Disease

ERIC Educational Resources Information Center

Silveri, Maria Caterina; Ciccarelli, Nicoletta; Baldonero, Eleonora; Piano, Carla; Zinno, Massimiliano; Soleti, Francesco; Bentivoglio, Anna Rita; Albanese, Alberto; Daniele, Antonio

2012-01-01

An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation…

A Dielectric Rod Antenna for Picosecond Pulse Stimulation of Neurological Tissue

PubMed Central

Petrella, Ross A.; Schoenbach, Karl H.; Xiao, Shu

2016-01-01

A dielectrically loaded wideband rod antenna has been studied as a pulse delivery system to subcutaneous tissues. Simulation results applying 100 ps electrical pulse show that it allows us to generate critical electric field for biological effects, such as brain stimulation, in the range of several centimeters. In order to reach the critical electric field for biological effects, which is approximately 20 kV/cm, at a depth of 2 cm, the input voltage needs to be 175 kV. The electric field spot size in the brain at this position is approximately 1 cm2. Experimental studies in free space with a conical antenna (part of the antenna system) with aluminum nitride as the dielectric have confirmed the accuracy of the simulation. These results set the foundation for high voltage in situ experiments on the complete antenna system and the delivery of pulses to biological tissue. PMID:27563160

Regional differences in mu and kappa opioid receptor G-protein activation in brain in male and female prairie voles.

PubMed

Martin, T J; Sexton, T; Kim, S A; Severino, A L; Peters, C M; Young, L J; Childers, S R

2015-12-17

Prairie voles are unusual mammals in that, like humans, they are capable of forming socially monogamous pair bonds, display biparental care, and engage in alloparental behaviors. Both mu and kappa opioid receptors are involved in behaviors that either establish and maintain, or result from pair bond formation in these animals. Mu and kappa opioid receptors both utilize inhibitory G-proteins in signal transduction mechanisms, however the efficacy by which these receptor subtypes stimulate G-protein signaling across the prairie vole neuraxis is not known. Utilizing [(35)S]GTPγS autoradiography, we characterized the efficacy of G-protein stimulation in coronal sections throughout male and female prairie vole brains by [D-Ala2,NMe-Phe4,Gly-ol5]-enkephalin (DAMGO) and U50,488H, selective mu and kappa opioid agonists, respectively. DAMGO stimulation was highest in the forebrain, similar to that found with other rodent species. U-50,488H produced greater stimulation in prairie voles than is typically seen in mice and rats, particularly in select forebrain areas. DAMGO produced higher stimulation in the core versus the shell of the nucleus accumbens (NAc) in females, while the distribution of U-50,488H stimulation was the opposite. There were no gender differences for U50,488H stimulation of G-protein activity across the regions examined, while DAMGO stimulation was greater in sections from females compared to those from males for NAc core, entopeduncular nucleus, and hippocampus. These data suggest that the kappa opioid system may be more sensitive to manipulation in prairie voles compared to mice and rats, and that female prairie voles may be more sensitive to mu agonists in select brain regions than males. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Acute effects of electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate in the cat: an evaluation of safety.

PubMed Central

Eyre, J A; Flecknell, P A; Kenyon, B R; Koh, T H; Miller, S

1990-01-01

The influence of repeated high intensity electromagnetic stimulation of the brain on cortical activity, cortical blood flow, blood pressure and heart rate has been investigated in the cat, to evaluate the safety of the method. The observations have been made in preparations under propofol anaesthesia before, during and after periods of anoxia. Electromagnetic stimulation of the brain evoked activity in descending motor pathways and was recorded by activity in the median nerve and by muscle twitches. Following repeated series of high intensity stimulation there were no systematic changes in somatosensory evoked potentials or background EEG, nor were there signs of epileptogenic activity during electromagnetic stimulation, before, during or after periods of anoxia. No systematic changes in cortical blood flow, blood pressure or heart rate were observed during electromagnetic stimulation, before or after periods of anoxia. In conclusion, no acute adverse consequences following electromagnetic stimulation in the normal and anoxic cat brain were demonstrated. PMID:2380732

The treatment of Parkinson's disease with deep brain stimulation: current issues

PubMed Central

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

Numerical dosimetry of transcranial magnetic stimulation coils

NASA Astrophysics Data System (ADS)

Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2014-03-01

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique capable of stimulating neurons by means of electromagnetic induction. TMS can be used to map brain function and shows promise for the diagnosis and treatment of neurological and psychiatric disorders. Calculation of fields induced in the brain are necessary to accurately identify stimulated neural tissue during TMS. This allows the development of novel TMS coil designs capable of stimulating deeper brain regions and increasing the localization of stimulation that can be achieved. We have performed numerical calculations of magnetic and electric field with high-resolution anatomically realistic human head models to find these stimulated brain regions for a variety of proposed TMS coil designs. The realistic head models contain heterogeneous tissue structures and electrical conductivities, yielding superior results to those obtained from the simplified homogeneous head models that are commonly employed. The attenuation of electric field as a function of depth in the brain and the localization of stimulating field have been methodically investigated. In addition to providing a quantitative comparison of different TMS coil designs the variation of induced field between subjects has been investigated. We also show the differences in induced fields between adult, adolescent and child head models to preemptively identify potential safety issues in the application of pediatric TMS.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

PubMed

Dmochowski, Jacek P; Koessler, Laurent; Norcia, Anthony M; Bikson, Marom; Parra, Lucas C

2017-08-15

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation

PubMed Central

Dmochowski, Jacek P.; Koessler, Laurent; Norcia, Anthony M.; Bikson, Marom; Parra, Lucas C.

2018-01-01

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4–7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. PMID:28578130

An adaptive model approach for quantitative wrist rigidity evaluation during deep brain stimulation surgery.

PubMed

Assis, Sofia; Costa, Pedro; Rosas, Maria Jose; Vaz, Rui; Silva Cunha, Joao Paulo

2016-08-01

Intraoperative evaluation of the efficacy of Deep Brain Stimulation includes evaluation of the effect on rigidity. A subjective semi-quantitative scale is used, dependent on the examiner perception and experience. A system was proposed previously, aiming to tackle this subjectivity, using quantitative data and providing real-time feedback of the computed rigidity reduction, hence supporting the physician decision. This system comprised of a gyroscope-based motion sensor in a textile band, placed in the patients hand, which communicated its measurements to a laptop. The latter computed a signal descriptor from the angular velocity of the hand during wrist flexion in DBS surgery. The first approach relied on using a general rigidity reduction model, regardless of the initial severity of the symptom. Thus, to enhance the performance of the previously presented system, we aimed to develop models for high and low baseline rigidity, according to the examiner assessment before any stimulation. This would allow a more patient-oriented approach. Additionally, usability was improved by having in situ processing in a smartphone, instead of a computer. Such system has shown to be reliable, presenting an accuracy of 82.0% and a mean error of 3.4%. Relatively to previous results, the performance was similar, further supporting the importance of considering the cogwheel rigidity to better infer about the reduction in rigidity. Overall, we present a simple, wearable, mobile system, suitable for intra-operatory conditions during DBS, supporting a physician in decision-making when setting stimulation parameters.

Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice.

PubMed

Toriizuka, K; Okumura, M; Iijima, K; Haruyama, K; Cyong, J C

1999-01-01

The effects of acupuncture on the disorders elicited by abnormalities of endocrine system were investigated in ovariectomized mice. Female mice (strain; C57BL/6) were ovariectomized (OVX) and acupuncture points, Shenshu ([Japanese pictograph see text] : BL23) on both side of the back were continuously stimulated by subcutaneous needles for 20 days. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for catecholamine contents by high performance liquid chromatography with electro chemical detector (ECD-HPLC). The mitogenic activities of splenic lymphocytes were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTS) assay and alkaline phosphatase (ALP) assay. Furthermore, the effects of needle stimulation on learning and memory ability were studied by the step-through type passive avoidance test. Norepinephrine and dopamine contents in the frontoparietal cerebral cortex, ventral hippocampus and olfactory bulb were decreased in the OVX group, and both MTS activity and ALP activity were decreased 20 days after ovariectomy. The mean latent period was also shortened in the passive avoidance test in the OVX group. However, applying needle stimulation increased norepinephrine and dopamine contents in the brain regions, and enhanced mitogenic activities of splenic lymphocytes. The stimulation also improved memory-related behavior. It was concluded from this study that after mice were stimulated by subcutaneous needle insertion, overall changes were observed in central nervous system (including retention of memory) and immune functions. The study suggests that acupuncture improves the memory loss and decrease of immune responses accompanying aging and/or menopause, and the that it may have an important role in medical care for the elderly.

Reducing the Disruptive Effects of Interruptions With Noninvasive Brain Stimulation.

PubMed

Blumberg, Eric J; Foroughi, Cyrus K; Scheldrup, Melissa R; Peterson, Matthew S; Boehm-Davis, Debbie A; Parasuraman, Raja

2015-09-01

The authors determine whether transcranial direct current stimulation (tDCS) can reduce resumption time when an ongoing task is interrupted. Interruptions are common and disruptive. Working memory capacity has been shown to predict resumption lag (i.e., time to successfully resume a task after interruption). Given that tDCS applied to brain areas associated with working memory can enhance performance, tDCS has the potential to improve resumption lag when a task is interrupted. Participants were randomly assigned to one of four groups that received anodal (active) stimulation of 2 mA tDCS to one of two target brain regions, left and right dorsolateral prefrontal cortex (DLPFC), or to one of two control areas, active stimulation of the left primary motor cortex or sham stimulation of the right DLPFC, while completing a financial management task that was intermittently interrupted with math problem solving. Anodal stimulation to the right and left DLPFC significantly reduced resumption lags compared to the control conditions (sham and left motor cortex stimulation). Additionally, there was no speed-accuracy tradeoff (i.e., the improvement in resumption time was not accompanied by an increased error rate). Noninvasive brain stimulation can significantly decrease resumption lag (improve performance) after a task is interrupted. Noninvasive brain stimulation offers an easy-to-apply tool that can significantly improve interrupted task performance. © 2014, Human Factors and Ergonomics Society.

Inter-subject Functional Correlation Reveal a Hierarchical Organization of Extrinsic and Intrinsic Systems in the Brain.

PubMed

Ren, Yudan; Nguyen, Vinh Thai; Guo, Lei; Guo, Christine Cong

2017-09-07

The brain is constantly monitoring and integrating both cues from the external world and signals generated intrinsically. These extrinsically and intrinsically-driven neural processes are thought to engage anatomically distinct regions, which are thought to constitute the extrinsic and intrinsic systems of the brain. While the specialization of extrinsic and intrinsic system is evident in primary and secondary sensory cortices, a systematic mapping of the whole brain remains elusive. Here, we characterized the extrinsic and intrinsic functional activities in the brain during naturalistic movie-viewing. Using a novel inter-subject functional correlation (ISFC) analysis, we found that the strength of ISFC shifts along the hierarchical organization of the brain. Primary sensory cortices appear to have strong inter-subject functional correlation, consistent with their role in processing exogenous information, while heteromodal regions that attend to endogenous processes have low inter-subject functional correlation. Those brain systems with higher intrinsic tendency show greater inter-individual variability, likely reflecting the aspects of brain connectivity architecture unique to individuals. Our study presents a novel framework for dissecting extrinsically- and intrinsically-driven processes, as well as examining individual differences in brain function during naturalistic stimulation.

Explaining how brain stimulation can evoke memories.

PubMed

Jacobs, Joshua; Lega, Bradley; Anderson, Christopher

2012-03-01

An unexplained phenomenon in neuroscience is the discovery that electrical stimulation in temporal neocortex can cause neurosurgical patients to spontaneously experience memory retrieval. Here we provide the first detailed examination of the neural basis of stimulation-induced memory retrieval by probing brain activity in a patient who reliably recalled memories of his high school (HS) after stimulation at a site in his left temporal lobe. After stimulation, this patient performed a customized memory task in which he was prompted to retrieve information from HS and non-HS topics. At the one site where stimulation evoked HS memories, remembering HS information caused a distinctive pattern of neural activity compared with retrieving non-HS information. Together, these findings suggest that the patient had a cluster of neurons in his temporal lobe that help represent the "high school-ness" of the current cognitive state. We believe that stimulation here evoked HS memories because it altered local neural activity in a way that partially mimicked the normal brain state for HS memories. More broadly, our findings suggest that brain stimulation can evoke memories by recreating neural patterns from normal cognition.

Computational electromagnetic methods for transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Gomez, Luis J.

Transcranial magnetic stimulation (TMS) is a noninvasive technique used both as a research tool for cognitive neuroscience and as a FDA approved treatment for depression. During TMS, coils positioned near the scalp generate electric fields and activate targeted brain regions. In this thesis, several computational electromagnetics methods that improve the analysis, design, and uncertainty quantification of TMS systems were developed. Analysis: A new fast direct technique for solving the large and sparse linear system of equations (LSEs) arising from the finite difference (FD) discretization of Maxwell's quasi-static equations was developed. Following a factorization step, the solver permits computation of TMS fields inside realistic brain models in seconds, allowing for patient-specific real-time usage during TMS. The solver is an alternative to iterative methods for solving FD LSEs, often requiring run-times of minutes. A new integral equation (IE) method for analyzing TMS fields was developed. The human head is highly-heterogeneous and characterized by high-relative permittivities (107). IE techniques for analyzing electromagnetic interactions with such media suffer from high-contrast and low-frequency breakdowns. The novel high-permittivity and low-frequency stable internally combined volume-surface IE method developed. The method not only applies to the analysis of high-permittivity objects, but it is also the first IE tool that is stable when analyzing highly-inhomogeneous negative permittivity plasmas. Design: TMS applications call for electric fields to be sharply focused on regions that lie deep inside the brain. Unfortunately, fields generated by present-day Figure-8 coils stimulate relatively large regions near the brain surface. An optimization method for designing single feed TMS coil-arrays capable of producing more localized and deeper stimulation was developed. Results show that the coil-arrays stimulate 2.4 cm into the head while stimulating 3.0 times less volume than Figure-8 coils. Uncertainty quantification (UQ): The location/volume/depth of the stimulated region during TMS is often strongly affected by variability in the position and orientation of TMS coils, as well as anatomical differences between patients. A surrogate model-assisted UQ framework was developed and used to statistically characterize TMS depression therapy. The framework identifies key parameters that strongly affect TMS fields, and partially explains variations in TMS treatment responses.

Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders

PubMed Central

SAAVEDRA, Juan M.

2012-01-01

The effects of brain AngII (angiotensin II) depend on AT1 receptor (AngII type 1 receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT1 receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood–brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT1 receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-β neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT1 receptor blockade, but also from PPARγ (peroxisome-proliferator-activated receptor γ) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer’s disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer’s disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic brain injury. PMID:22827472

Noninvasive brain stimulation to suppress craving in substance use disorders: review of human evidence and methodological considerations for future work

PubMed Central

Hone-Blanchet, Antoine; Ciraulo, Domenic A; Pascual-Leone, Alvaro; Fecteau, Shirley

2016-01-01

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of non-invasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of non-invasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects’ characteristics. PMID:26449761

Noninvasive brain stimulation to suppress craving in substance use disorders: Review of human evidence and methodological considerations for future work.

PubMed

Hone-Blanchet, Antoine; Ciraulo, Domenic A; Pascual-Leone, Alvaro; Fecteau, Shirley

2015-12-01

Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of noninvasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of noninvasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects' characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery

PubMed Central

Liew, Sook-Lei; Santarnecchi, Emilliano; Buch, Ethan R.; Cohen, Leonardo G.

2014-01-01

Non-invasive brain stimulation (NIBS) may enhance motor recovery after neurological injury through the causal induction of plasticity processes. Neurological injury, such as stroke, often results in serious long-term physical disabilities, and despite intensive therapy, a large majority of brain injury survivors fail to regain full motor function. Emerging research suggests that NIBS techniques, such as transcranial magnetic (TMS) and direct current (tDCS) stimulation, in association with customarily used neurorehabilitative treatments, may enhance motor recovery. This paper provides a general review on TMS and tDCS paradigms, the mechanisms by which they operate and the stimulation techniques used in neurorehabilitation, specifically stroke. TMS and tDCS influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. We discuss recent studies that document NIBS effects on global brain activity measured with various neuroimaging techniques, which help to characterize better strategies for more accurate NIBS stimulation. These rapidly growing areas of inquiry may hold potential for improving the effectiveness of NIBS-based interventions for clinical rehabilitation. PMID:25018714

A new brain stimulation method: Noninvasive transcranial magneto-acoustical stimulation

NASA Astrophysics Data System (ADS)

Yuan, Yi; Chen, Yu-Dong; Li, Xiao-Li

2016-08-01

We investigate transcranial magneto-acoustical stimulation (TMAS) for noninvasive brain neuromodulation in vivo. TMAS as a novel technique uses an ultrasound wave to induce an electric current in the brain tissue in the static magnetic field. It has the advantage of high spatial resolution and penetration depth. The mechanism of TMAS onto a neuron is analyzed by combining the TMAS principle and Hodgkin-Huxley neuron model. The anesthetized rats are stimulated by TMAS, resulting in the local field potentials which are recorded and analyzed. The simulation results show that TMAS can induce neuronal action potential. The experimental results indicate that TMAS can not only increase the amplitude of local field potentials but also enhance the effect of focused ultrasound stimulation on the neuromodulation. In summary, TMAS can accomplish brain neuromodulation, suggesting a potentially powerful noninvasive stimulation method to interfere with brain rhythms for diagnostic and therapeutic purposes. Project supported by the National Natural Science Foundation of China (Grant Nos. 61503321 and 61273063) and the Natural Science Foundation of Hebei Province, China (Grant No. F2014203161).

Activation of sensory cortex by imagined genital stimulation: an fMRI analysis

PubMed Central

Wise, Nan J.; Frangos, Eleni; Komisaruk, Barry R.

2016-01-01

Background During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. Objective This study extends our previous findings by further characterizing how the brain differentially processes physical ‘touch’ stimulation and ‘imagined’ stimulation. Design Eleven healthy women (age range 29–74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions – imagined dildo self-stimulation and imagined speculum stimulation – were included to characterize the effects of erotic versus non-erotic imagery. Results Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. Conclusion The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the ‘reward system’. In addition, these results suggest a mechanism by which some individuals may be able to generate orgasm by imagery in the absence of physical stimulation. PMID:27791966

Interleukin-1 Receptor Activation by Systemic Lipopolysaccharide Induces Behavioral Despair Linked to MAPK Regulation of CNS Serotonin Transporters

PubMed Central

Zhu, Chong-Bin; Lindler, Kathryn M; Owens, Anthony W; Daws, Lynette C; Blakely, Randy D; Hewlett, William A

2010-01-01

Serotonin (5-hydroxytryptamine, 5-HT) has long been implicated in regulation of mood. Medications that block the neuronal 5-HT transporter (SERT) are used as major pharmacological treatment for mood disorders. Conversely, stimuli that enhance SERT activity might be predicted to diminish synaptic 5-HT availability and increase the risk for 5-HT-related CNS disorders. We have shown that the inflammatory cytokines enhance brain SERT activity in cultured serotonergic cells and nerve terminal preparations in vitro. In this study, we establish that intraperitoneal injection of the cytokine-inducer lipopolysaccharide (LPS) stimulates brain SERT activity, acting at doses below those required to induce overt motor suppression. SERT stimulation by LPS is paralleled by increased immobility in both the tail suspension test (TST) and the forced swim test (FST); antidepressant-sensitive alterations are thought to model aspects of behavioral despair. Both the stimulation of SERT activity and induced immobility are absent when LPS is administered to interleukin-1 receptor (IL-1R)-deficient mice and in the presence of SB203580, an inhibitor of IL-1R-stimulated p38 MAPK. Moreover, the ability of LPS to enhance immobility in TST is lost in SERT knockout mice. These findings reveal an ability of peripheral inflammatory stimuli to enhance brain SERT activity through IL-1R and p38 MAPK pathways in vivo and identify a requirement for SERT expression in immune-system-modulated despair behaviors. Our studies identify IL-1R- and p38 MAPK-dependent regulation of SERT as one of the mechanisms by which environmentally driven immune system activation can trigger despair-like behavior in an animal model, encouraging future analysis of the pathway for risk factors in neuropsychiatric disorders. PMID:20827273

Neuroscience and Learning: Lessons from Studying the Involvement of a Region of Cerebellar Cortex in Eyeblink Classical Conditioning

ERIC Educational Resources Information Center

Villarreal, Ronald P.; Steinmetz, Joseph E.

2005-01-01

How the nervous system encodes learning and memory processes has interested researchers for 100 years. Over this span of time, a number of basic neuroscience methods has been developed to explore the relationship between learning and the brain, including brain lesion, stimulation, pharmacology, anatomy, imaging, and recording techniques. In this…

An investigation into the induced electric fields from transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Hadimani, Ravi; Lee, Erik; Duffy, Walter; Waris, Mohammed; Siddiqui, Waquar; Islam, Faisal; Rajamani, Mahesh; Nathan, Ryan; Jiles, David; David C Jiles Team; Walter Duffy Collaboration

Transcranial magnetic stimulation (TMS) is a promising tool for noninvasive brain stimulation that has been approved by the FDA for the treatment of major depressive disorder. To stimulate the brain, TMS uses large, transient pulses of magnetic field to induce an electric field in the head. This transient magnetic field is large enough to cause the depolarization of cortical neurons and initiate a synaptic signal transmission. For this study, 50 unique head models were created from MRI images. Previous simulation studies have primarily used a single head model, and thus give a limited image of the induced electric field from TMS. This study uses finite element analysis simulations on 50 unique, heterogeneous head models to better investigate the relationship between TMS and the electric field induced in brain tissues. Results showed a significant variation in the strength of the induced electric field in the brain, which can be reasonably predicted by the distance from the TMS coil to the stimulated brain. Further, it was seen that some models had high electric field intensities in over five times as much brain volume as other models.

Adaptive deep brain stimulation in advanced Parkinson disease.

PubMed

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

2013-09-01

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

Modulatory Effect of Association of Brain Stimulation by Light and Binaural Beats in Specific Brain Waves

PubMed Central

Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza e Silva, Alair Pedro

2017-01-01

Introduction: One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. Subjects: The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson’s disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer’s disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments and procedure: Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. Results: The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. Conclusion: The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies. PMID:29238390

Modulatory Effect of Association of Brain Stimulation by Light and Binaural Beats in Specific Brain Waves.

PubMed

Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza E Silva, Alair Pedro

2017-01-01

One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson's disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer's disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies.

A primer on brain-machine interfaces, concepts, and technology: a key element in the future of functional neurorestoration.

PubMed

Lee, Brian; Liu, Charles Y; Apuzzo, Michael L J

2013-01-01

Conventionally, the practice of neurosurgery has been characterized by the removal of pathology, congenital or acquired. The emerging complement to the removal of pathology is surgery for the specific purpose of restoration of function. Advents in neuroscience, technology, and the understanding of neural circuitry are creating opportunities to intervene in disease processes in a reparative manner, thereby advancing toward the long-sought-after concept of neurorestoration. Approaching the issue of neurorestoration from a biomedical engineering perspective is the rapidly growing arena of implantable devices. Implantable devices are becoming more common in medicine and are making significant advancements to improve a patient's functional outcome. Devices such as deep brain stimulators, vagus nerve stimulators, and spinal cord stimulators are now becoming more commonplace in neurosurgery as we utilize our understanding of the nervous system to interpret neural activity and restore function. One of the most exciting prospects in neurosurgery is the technologically driven field of brain-machine interface, also known as brain-computer interface, or neuroprosthetics. The successful development of this technology will have far-reaching implications for patients suffering from a great number of diseases, including but not limited to spinal cord injury, paralysis, stroke, or loss of limb. This article provides an overview of the issues related to neurorestoration using implantable devices with a specific focus on brain-machine interface technology. Copyright © 2013 Elsevier Inc. All rights reserved.

Improvements in Attention and Decision-Making Following Combined Behavioral Training and Brain Stimulation.

PubMed

Filmer, Hannah L; Varghese, Elizabeth; Hawkins, Guy E; Mattingley, Jason B; Dux, Paul E

2017-07-01

In recent years there has been a significant commercial interest in 'brain training' - massed or spaced practice on a small set of tasks to boost cognitive performance. Recently, researchers have combined cognitive training regimes with brain stimulation to try and maximize training benefits, leading to task-specific cognitive enhancement. It remains unclear, however, whether the performance gains afforded by such regimes can transfer to untrained tasks, or how training and stimulation affect the brain's latent information processing dynamics. To examine these issues, we applied transcranial direct current stimulation (tDCS) over the prefrontal cortex while participants undertook decision-making training over several days. Anodal, relative to cathodal/sham tDCS, increased performance gains from training. Critically, these gains were reliable for both trained and untrained tasks. The benefit of anodal tDCS occurred for left, but not right, prefrontal stimulation, and was absent for stimulation delivered without concurrent training. Modeling revealed left anodal stimulation combined with training caused an increase in the brain's rate of evidence accumulation for both tasks. Thus tDCS applied during training has the potential to modulate training gains and give rise to transferable performance benefits for distinct cognitive operations through an increase in the rate at which the brain acquires information. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface

PubMed Central

Su, Yi; Routhu, Sudhamayee; Moon, Kee S.; Lee, Sung Q.; Youm, WooSub; Ozturk, Yusuf

2016-01-01

All neural information systems (NIS) rely on sensing neural activity to supply commands and control signals for computers, machines and a variety of prosthetic devices. Invasive systems achieve a high signal-to-noise ratio (SNR) by eliminating the volume conduction problems caused by tissue and bone. An implantable brain machine interface (BMI) using intracortical electrodes provides excellent detection of a broad range of frequency oscillatory activities through the placement of a sensor in direct contact with cortex. This paper introduces a compact-sized implantable wireless 32-channel bidirectional brain machine interface (BBMI) to be used with freely-moving primates. The system is designed to monitor brain sensorimotor rhythms and present current stimuli with a configurable duration, frequency and amplitude in real time to the brain based on the brain activity report. The battery is charged via a novel ultrasonic wireless power delivery module developed for efficient delivery of power into a deeply-implanted system. The system was successfully tested through bench tests and in vivo tests on a behaving primate to record the local field potential (LFP) oscillation and stimulate the target area at the same time. PMID:27669264

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

PubMed

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

2017-08-01

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

Design and Application of a Circuit for Measuring Frequency and Duty Cycle of Stimulated Bioelectrical Signal

NASA Astrophysics Data System (ADS)

Tang, Li-Ming; Chang, Ben-Kang; Liu, Tie-Bing; Wu, Min; Ling, Gang

2002-12-01

To design a new type of circuit for measuring frequency & duty cycle of stimulated bioelectrical signal for the project of 'the map of neuron-threshold in human brain and its clinical application'. This circuit was designed according to the character of stimulated bioelectrical signals. It was tested and improved and then used in the neuron -threshold stimulator. The circuit was found to be very accurate for measuring frequency and the error for measuring duty cycle was below 0.2%. This circuit is well-designed, simple, easy to use, and can be applied in many systems.

Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

PubMed

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 brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

Using Proton Magnetic Resonance Imaging and Spectroscopy to Understand Brain "Activation"

ERIC Educational Resources Information Center

Baslow, Morris H.; Guilfoyle, David N.

2007-01-01

Upon stimulation, areas of the brain associated with specific cognitive processing tasks may undergo observable physiological changes, and measures of such changes have been used to create brain maps for visualization of stimulated areas in task-related brain "activation" studies. These perturbations usually continue throughout the period of the…

Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

PubMed Central

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

Neuroengineering tools/applications for bidirectional interfaces, brain-computer interfaces, and neuroprosthetic implants - a review of recent progress.

PubMed

Rothschild, Ryan Mark

2010-01-01

The main focus of this review is to provide a holistic amalgamated overview of the most recent human in vivo techniques for implementing brain-computer interfaces (BCIs), bidirectional interfaces, and neuroprosthetics. Neuroengineering is providing new methods for tackling current difficulties; however neuroprosthetics have been studied for decades. Recent progresses are permitting the design of better systems with higher accuracies, repeatability, and system robustness. Bidirectional interfaces integrate recording and the relaying of information from and to the brain for the development of BCIs. The concepts of non-invasive and invasive recording of brain activity are introduced. This includes classical and innovative techniques like electroencephalography and near-infrared spectroscopy. Then the problem of gliosis and solutions for (semi-) permanent implant biocompatibility such as innovative implant coatings, materials, and shapes are discussed. Implant power and the transmission of their data through implanted pulse generators and wireless telemetry are taken into account. How sensation can be relayed back to the brain to increase integration of the neuroengineered systems with the body by methods such as micro-stimulation and transcranial magnetic stimulation are then addressed. The neuroprosthetic section discusses some of the various types and how they operate. Visual prosthetics are discussed and the three types, dependant on implant location, are examined. Auditory prosthetics, being cochlear or cortical, are then addressed. Replacement hand and limb prosthetics are then considered. These are followed by sections concentrating on the control of wheelchairs, computers and robotics directly from brain activity as recorded by non-invasive and invasive techniques.

Neuromechanism Study of Insect–Machine Interface: Flight Control by Neural Electrical Stimulation

PubMed Central

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A.; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect–machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee–machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control. PMID:25409523

Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

PubMed

Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

2014-01-01

The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

External trial deep brain stimulation device for the application of desynchronizing stimulation techniques.

PubMed

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.

Magnetothermal genetic deep brain stimulation of motor behaviors in awake, freely moving mice

PubMed Central

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

Noninvasive near-infrared topography of human brain activity using intensity modulation spectroscopy

NASA Astrophysics Data System (ADS)

Yamashita, Yuichi; Maki, Atsushi; Ito, Yoshitoshi; Watanabe, Eiju; Mayanagi, Yoshiaki; Koizumi, Hideaki

1996-04-01

We describe the functional topography of human brain activity due to motor stimulation by using near-infrared spectroscopy. Finger motion by each hand was used as the motor stimulation, and activity in the left fronto-central region of the brain was measured. A greater change in oxyhemoglobin concentration due to brain activity during the stimulation was obtained for the right hand than for the left hand. Localization of the activity was obtained by topographically mapping the measured changes for ten positions within the region.

Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

PubMed

Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

2008-02-01

Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes

PubMed Central

Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L.; Kay, Steven M.; Besio, Walter G.

2012-01-01

Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback. PMID:22772373

Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L; Kay, Steven M; Besio, Walter G

2012-07-01

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study, we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback.

Evaluation of Interactive Visualization on Mobile Computing Platforms for Selection of Deep Brain Stimulation Parameters

PubMed Central

Butson, Christopher R.; Tamm, Georg; Jain, Sanket; Fogal, Thomas; Krüger, Jens

2012-01-01

In recent years there has been significant growth in the use of patient-specific models to predict the effects of neuromodulation therapies such as deep brain stimulation (DBS). However, translating these models from a research environment to the everyday clinical workflow has been a challenge, primarily due to the complexity of the models and the expertise required in specialized visualization software. In this paper, we deploy the interactive visualization system ImageVis3D Mobile, which has been designed for mobile computing devices such as the iPhone or iPad, in an evaluation environment to visualize models of Parkinson’s disease patients who received DBS therapy. Selection of DBS settings is a significant clinical challenge that requires repeated revisions to achieve optimal therapeutic response, and is often performed without any visual representation of the stimulation system in the patient. We used ImageVis3D Mobile to provide models to movement disorders clinicians and asked them to use the software to determine: 1) which of the four DBS electrode contacts they would select for therapy; and 2) what stimulation settings they would choose. We compared the stimulation protocol chosen from the software versus the stimulation protocol that was chosen via clinical practice (independently of the study). Lastly, we compared the amount of time required to reach these settings using the software versus the time required through standard practice. We found that the stimulation settings chosen using ImageVis3D Mobile were similar to those used in standard of care, but were selected in drastically less time. We show how our visualization system, available directly at the point of care on a device familiar to the clinician, can be used to guide clinical decision making for selection of DBS settings. In our view, the positive impact of the system could also translate to areas other than DBS. PMID:22450824

Analysis of Oscillatory Neural Activity in Series Network Models of Parkinson's Disease During Deep Brain Stimulation.

PubMed

Davidson, Clare M; de Paor, Annraoi M; Cagnan, Hayriye; Lowery, Madeleine M

2016-01-01

Parkinson's disease is a progressive, neurodegenerative disorder, characterized by hallmark motor symptoms. It is associated with pathological, oscillatory neural activity in the basal ganglia. Deep brain stimulation (DBS) is often successfully used to treat medically refractive Parkinson's disease. However, the selection of stimulation parameters is based on qualitative assessment of the patient, which can result in a lengthy tuning period and a suboptimal choice of parameters. This study explores fourth-order, control theory-based models of oscillatory activity in the basal ganglia. Describing function analysis is applied to examine possible mechanisms for the generation of oscillations in interacting nuclei and to investigate the suppression of oscillations with high-frequency stimulation. The theoretical results for the suppression of the oscillatory activity obtained using both the fourth-order model, and a previously described second-order model, are optimized to fit clinically recorded local field potential data obtained from Parkinsonian patients with implanted DBS. Close agreement between the power of oscillations recorded for a range of stimulation amplitudes is observed ( R(2)=0.69-0.99 ). The results suggest that the behavior of the system and the suppression of pathological neural oscillations with DBS is well described by the macroscopic models presented. The results also demonstrate that in this instance, a second-order model is sufficient to model the clinical data, without the need for added complexity. Describing the system behavior with computationally efficient models could aid in the identification of optimal stimulation parameters for patients in a clinical environment.

Characterization of particulate cyclic nucleotide phosphodiesterases from bovine brain: Purification of a distinct cGMP-stimulated isoenzyme

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

Murashima, Seiko; Tanaka, Takayuki; Hockman, S.

1990-06-05

In the absence of detergent, {approx}80-85% of the total cGMP-stimulated phosphodiesterase (PDE) activity in bovine brain was associated with washed particulate fractions; {approx}85-90% of the calmodulin-sensitive PDE was soluble. Particulate cGMP-stimulated PDE was higher in cerebral cortical gray matter than in other regions. Homogenization of the brain particulate fraction in 1% Lubrol increased cGMP-stimulated activity {approx}100% and calmodulin-stimulated {approx}400-500%. Although 1% Lubrol readily solubilized these PDE activities, {approx}75% of the cAMP PDE activity (0.5 {mu}M ({sup 3}H)cAMP) that was not affected by cGMP was not solubilized. This cAMP PDE activity was very sensitive to inhibition by Rolipram but not cilostamide.more » Thus, three different PDE types, i.e., cGMP stimulated, calmodulin sensitive, and Rolipram inhibited, are associated in different ways with crude bovine brain particulate fractions. The brain enzyme exhibited a slightly greater subunit M{sub r} than did soluble forms from calf liver or bovine brain, as evidenced by protein staining or immunoblotting after polyacrylamide gel electrophoresis under denaturing conditions. Incubation of brain particulate and liver soluble cGMP-stimulated PDEs with V{sub 8} protease produced several peptides of similar size, as well as at least two distinct fragments of {approx}27 kDa from the brain and {approx}23 kDa from the liver enzyme. After photolabeling in the presence of ({sup 32}P)cGMP and digestion with V{sub 8} protease, ({sup 32}P)cGMP in each PDE was predominantly recovered with a peptide of {approx}14 kDa. All of these observations are consistent with the existence of at least two discrete forms (isoenzymes) of cGMP-stimulated PDE.« less

The sleeping brain as a complex system.

PubMed

Olbrich, Eckehard; Achermann, Peter; Wennekers, Thomas

2011-10-13

'Complexity science' is a rapidly developing research direction with applications in a multitude of fields that study complex systems consisting of a number of nonlinear elements with interesting dynamics and mutual interactions. This Theme Issue 'The complexity of sleep' aims at fostering the application of complexity science to sleep research, because the brain in its different sleep stages adopts different global states that express distinct activity patterns in large and complex networks of neural circuits. This introduction discusses the contributions collected in the present Theme Issue. We highlight the potential and challenges of a complex systems approach to develop an understanding of the brain in general and the sleeping brain in particular. Basically, we focus on two topics: the complex networks approach to understand the changes in the functional connectivity of the brain during sleep, and the complex dynamics of sleep, including sleep regulation. We hope that this Theme Issue will stimulate and intensify the interdisciplinary communication to advance our understanding of the complex dynamics of the brain that underlies sleep and consciousness.

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

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.

The point spread function of the human head and its implications for transcranial current stimulation

NASA Astrophysics Data System (ADS)

Dmochowski, Jacek P.; Bikson, Marom; Parra, Lucas C.

2012-10-01

Rational development of transcranial current stimulation (tCS) requires solving the ‘forward problem’: the computation of the electric field distribution in the head resulting from the application of scalp currents. Derivation of forward models has represented a major effort in brain stimulation research, with model complexity ranging from spherical shells to individualized head models based on magnetic resonance imagery. Despite such effort, an easily accessible benchmark head model is greatly needed when individualized modeling is either undesired (to observe general population trends as opposed to individual differences) or unfeasible. Here, we derive a closed-form linear system which relates the applied current to the induced electric potential. It is shown that in the spherical harmonic (Fourier) domain, a simple scalar multiplication relates the current density on the scalp to the electric potential in the brain. Equivalently, the current density in the head follows as the spherical convolution between the scalp current distribution and the point spread function of the head, which we derive. Thus, if one knows the spherical harmonic representation of the scalp current (i.e. the electrode locations and current intensity to be employed), one can easily compute the resulting electric field at any point inside the head. Conversely, one may also readily determine the scalp current distribution required to generate an arbitrary electric field in the brain (the ‘backward problem’ in tCS). We demonstrate the simplicity and utility of the model with a series of characteristic curves which sweep across a variety of stimulation parameters: electrode size, depth of stimulation, head size and anode-cathode separation. Finally, theoretically optimal montages for targeting an infinitesimal point in the brain are shown.

Non-invasive Brain Stimulation in the Treatment of Post-stroke and Neurodegenerative Aphasia: Parallels, Differences, and Lessons Learned

PubMed Central

Norise, Catherine; Hamilton, Roy H.

2017-01-01

Numerous studies over the span of more than a decade have shown that non-invasive brain stimulation (NIBS) techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can facilitate language recovery for patients who have suffered from aphasia due to stroke. While stroke is the most common etiology of aphasia, neurodegenerative causes of language impairment—collectively termed primary progressive aphasia (PPA)—are increasingly being recognized as important clinical phenotypes in dementia. Very limited data now suggest that (NIBS) may have some benefit in treating PPAs. However, before applying the same approaches to patients with PPA as have previously been pursued in patients with post-stroke aphasia, it will be important for investigators to consider key similarities and differences between these aphasia etiologies that is likely to inform successful approaches to stimulation. While both post-stroke aphasia and the PPAs have clear overlaps in their clinical phenomenology, the mechanisms of injury and theorized neuroplastic changes associated with the two etiologies are notably different. Importantly, theories of plasticity in post-stroke aphasia are largely predicated on the notion that regions of the brain that had previously been uninvolved in language processing may take on new compensatory roles. PPAs, however, are characterized by slow distributed degeneration of cellular units within the language system; compensatory recruitment of brain regions to subserve language is not currently understood to be an important aspect of the condition. This review will survey differences in the mechanisms of language representation between the two etiologies of aphasia and evaluate properties that may define and limit the success of different neuromodulation approaches for these two disorders. PMID:28167904

An Arbitrary Waveform Wearable Neuro-stimulator System for Neurophysiology Research on Freely Behaving Animals.

PubMed

Samani, Mohsen Mosayebi; Mahnam, Amin; Hosseini, Nasrin

2014-04-01

Portable wireless neuro-stimulators have been developed to facilitate long-term cognitive and behavioral studies on the central nervous system in freely moving animals. These stimulators can provide precisely controllable input(s) to the nervous system, without distracting the animal attention with cables connected to its body. In this study, a low power backpack neuro-stimulator was developed for animal brain researches that can provides arbitrary stimulus waveforms for the stimulation, while it is small and light weight to be used for small animals including rats. The system consists of a controller that uses an RF link to program and activate a small and light microprocessor-based stimulator. A Howland current source was implemented to produce precise current controlled arbitrary waveform stimulations. The system was optimized for ultra-low power consumption and small size. The stimulator was first tested for its electrical specifications. Then its performance was evaluated in a rat experiment when electrical stimulation of medial longitudinal fasciculus induced circling behavior. The stimulator is capable of delivering programmed stimulations up to ± 2 mA with adjusting steps of 1 μA, accuracy of 0.7% and compliance of 6 V. The stimulator is 15 mm × 20 mm × 40 mm in size, weights 13.5 g without battery and consumes a total power of only 5.l mW. In the experiment, the rat could easily carry the stimulator and demonstrated the circling behavior for 0.1 ms current pulses of above 400 μA. The developed system has a competitive size and weight, whereas providing a wide range of operation and the flexibility of generating arbitrary stimulation patterns ideal for long-term experiments in the field of cognitive and neuroscience research.

Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis

PubMed Central

Grahn, Peter J.; Mallory, Grant W.; Berry, B. Michael; Hachmann, Jan T.; Lobel, Darlene A.; Lujan, J. Luis

2014-01-01

Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI) can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system's state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles. PMID:25278830

Different brain activation under left and right ventricular stimulation: an fMRI study in anesthetized rats.

PubMed

Suzuki, Hideaki; Sumiyoshi, Akira; Kawashima, Ryuta; Shimokawa, Hiroaki

2013-01-01

Myocardial ischemia in the anterior wall of the left ventricule (LV) and in the inferior wall and/or right ventricle (RV) shows different manifestations that can be explained by the different innervations of cardiac afferent nerves. However, it remains unclear whether information from different areas of the heart, such as the LV and RV, are differently processed in the brain. In this study, we investigated the brain regions that process information from the LV or RV using cardiac electrical stimulation and functional magnetic resonance imaging (fMRI) in anesthetized rats because the combination of these two approaches cannot be used in humans. An electrical stimulation catheter was inserted into the LV or RV (n = 12 each). Brain fMRI scans were recorded during LV or RV stimulation (9 Hz and 0.3 ms width) over 10 blocks consisting of alternating periods of 2 mA for 30 sec followed by 0.2 mA for 60 sec. The validity of fMRI signals was confirmed by first and second-level analyses and temporal profiles. Increases in fMRI signals were observed in the anterior cingulate cortex and the right somatosensory cortex under LV stimulation. In contrast, RV stimulation activated the right somatosensory cortex, which was identified more anteriorly compared with LV stimulation but did not activate the anterior cingulate cortex. This study provides the first evidence for differences in brain activation under LV and RV stimulation. These different brain processes may be associated with different clinical manifestations between anterior wall and inferoposterior wall and/or RV myocardial ischemia.

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation.

PubMed

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S; Weisz, Nathan

2015-09-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. Copyright © 2015. Published by Elsevier Inc.

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation

PubMed Central

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S.; Weisz, Nathan

2015-01-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. PMID:26080310

Intersubject synchronisation analysis of brain activity associated with the instant effects of acupuncture: an fMRI study.

PubMed

Jin, Lingmin; Sun, Jinbo; Xu, Ziliang; Yang, Xuejuan; Liu, Peng; Qin, Wei

2018-02-01

To use a promising analytical method, namely intersubject synchronisation (ISS), to evaluate the brain activity associated with the instant effects of acupuncture and compare the findings with traditional general linear model (GLM) methods. 30 healthy volunteers were recruited for this study. Block-designed manual acupuncture stimuli were delivered at SP6, and de qi sensations were measured after acupuncture stimulation. All subjects underwent functional MRI (fMRI) scanning during the acupuncture stimuli. The fMRI data were separately analysed by ISS and traditional GLM methods. All subjects experienced de qi sensations. ISS analysis showed that the regions activated during acupuncture stimulation at SP6 were mainly divided into five clusters based on the time courses. The time courses of clusters 1 and 2 were in line with the acupuncture stimulation pattern, and the active regions were mainly involved in the sensorimotor system and salience network. Clusters 3, 4 and 5 displayed an almost contrary time course relative to the stimulation pattern. The brain regions activated included the default mode network, descending pain modulation pathway and visual cortices. GLM analysis indicated that the brain responses associated with the instant effects of acupuncture were largely implicated in sensory and motor processing and sensory integration. The ISS analysis considered the sustained effect of acupuncture and uncovered additional information not shown by GLM analysis. We suggest that ISS may be a suitable approach to investigate the brain responses associated with the instant effects of acupuncture. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Activation of the DLPFC Reveals an Asymmetric Effect in Risky Decision Making: Evidence from a tDCS Study

PubMed Central

Huang, Daqiang; Chen, Shu; Wang, Siqi; Shi, Jinchuan; Ye, Hang; Luo, Jun; Zheng, Haoli

2017-01-01

The phenomenon of loss aversion (the tendency for losses to have a greater impact than comparable gains) has long been observed in daily life. Neurocognitive studies and brain imaging studies have shed light on the correlation between the phenomenon of loss aversion and the brain region of the prefrontal cortex. Recent brain stimulation studies using bilateral transcranial magnetic stimulation or transcranial direct current stimulation (tDCS) have obtained various results showing the causal relationship between brain regions and decision making. With the goal of studying whether unilateral stimulation can change participants’ risky decision making in the frames of gains and losses, we applied different polarities of tDCS over the regions of the right or left prefrontal cortex. We also designed a risk measurement table (Multiple Price List) to reflect the participants’ attitudes toward risky decision making via the crossover point including the frames of gains and losses. The results of our experiment indicated that the participants tended to be more risk averse in the gain frame after receiving left anodal tDCS and more risk seeking in the loss frame after receiving right cathodal tDCS, which was consistent with the hypothesis that the process of risky decision making was correlated with the interaction of multiple systems in the brain. Our conclusion revealed an asymmetric effect of right/left DLPFC when the participants faced gains and losses, which partially provided the neural evidence and a feasible paradigm to help better understand risky decision making and loss aversion. The current study can not only expand the traditional understanding of the behavioral preferences of humans in economics but also accommodate empirical observations of behavioral economists on the preferences of humans. PMID:28174549

Electromagnetic interference of GSM mobile phones with the implantable deep brain stimulator, ITREL-III

PubMed Central

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

Non-invasive Brain Stimulation: A Paradigm Shift in Understanding Brain Oscillations.

PubMed

Vosskuhl, Johannes; Strüber, Daniel; Herrmann, Christoph S

2018-01-01

Cognitive neuroscience set out to understand the neural mechanisms underlying cognition. One central question is how oscillatory brain activity relates to cognitive processes. Up to now, most of the evidence supporting this relationship was correlative in nature. This situation changed dramatically with the recent development of non-invasive brain stimulation (NIBS) techniques, which open up new vistas for neuroscience by allowing researchers for the first time to validate their correlational theories by manipulating brain functioning directly. In this review, we focus on transcranial alternating current stimulation (tACS), an electrical brain stimulation method that applies sinusoidal currents to the intact scalp of human individuals to directly interfere with ongoing brain oscillations. We outline how tACS can impact human brain oscillations by employing different levels of observation from non-invasive tACS application in healthy volunteers and intracranial recordings in patients to animal studies demonstrating the effectiveness of alternating electric fields on neurons in vitro and in vivo . These findings likely translate to humans as comparable effects can be observed in human and animal studies. Neural entrainment and plasticity are suggested to mediate the behavioral effects of tACS. Furthermore, we focus on mechanistic theories about the relationship between certain cognitive functions and specific parameters of brain oscillaitons such as its amplitude, frequency, phase and phase coherence. For each of these parameters we present the current state of testing its functional relevance by means of tACS. Recent developments in the field of tACS are outlined which include the stimulation with physiologically inspired non-sinusoidal waveforms, stimulation protocols which allow for the observation of online-effects, and closed loop applications of tACS.

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Design of robust adaptive controller and feedback error learning for rehabilitation in Parkinson's disease: a simulation study.

PubMed

Rouhollahi, Korosh; Emadi Andani, Mehran; Karbassi, Seyed Mahdi; Izadi, Iman

2017-02-01

Deep brain stimulation (DBS) is an efficient therapy to control movement disorders of Parkinson's tremor. Stimulation of one area of basal ganglia (BG) by DBS with no feedback is the prevalent opinion. Reduction of additional stimulatory signal delivered to the brain is the advantage of using feedback. This results in reduction of side effects caused by the excessive stimulation intensity. In fact, the stimulatory intensity of controllers is decreased proportional to reduction of hand tremor. The objective of this study is to design a new controller structure to decrease three indicators: (i) the hand tremor; (ii) the level of delivered stimulation in disease condition; and (iii) the ratio of the level of delivered stimulation in health condition to disease condition. For this purpose, the authors offer a new closed-loop control structure to stimulate two areas of BG simultaneously. One area (STN: subthalamic nucleus) is stimulated by an adaptive controller with feedback error learning. The other area (GPi: globus pallidus internal) is stimulated by a partial state feedback (PSF) controller. Considering the three indicators, the results show that, stimulating two areas simultaneously leads to better performance compared with stimulating one area only. It is shown that both PSF and adaptive controllers are robust regarding system parameter uncertainties. In addition, a method is proposed to update the parameters of the BG model in real time. As a result, the parameters of the controllers can be updated based on the new parameters of the BG model.

[Passive tactile stimulation and its clinical and neurophysiological repercussions (P300) in blind children with symptoms of attention deficit disorder].

PubMed

Serrano-Marugán, Isabel; Herrera, Begoña; Romero, Sara; Nogales, Ramón; Poch-Broto, Joaquín; Quintero, Javier; Ortiz, Tomás

2014-02-24

Tactile stimulation is key for the posterior brain re-organization activity and attention processes, however the impact of tactile stimulation on attention deficit disorder (ADD) in blind children remains unexplored. We carried out a study with children having or not ADD (four per group). The subjects have been exposed during six months to tactile stimulation protocol consisting in two daily sessions (morning and afternoon sessions) of 30 minutes each. We have measured the ability to detect an infrequent tactile stimulus, reaction time, latency of P300, sources of brain activity, and ADD clinical symptoms, before and after tactile training. Passive tactile stimulation significantly improves ADD clinical symptoms, particularly attention, behavior and self-control of involuntary movements and tics. In addition, tactile stimulation changes the pattern of brain activity in ADD blind children inducing activity in frontal and occipital areas, which could be associated to a compensation of the attention deficit. Passive tactile stimulation training may improve ADD clinical symptoms and can reorganize the pattern of brain activity in blind ADD children.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper

PubMed Central

Thut, Gregor; Bergmann, Til Ole; Fröhlich, Flavio; Soekadar, Surjo R.; Brittain, John-Stuart; Valero-Cabré, Antoni; Sack, Alexander; Miniussi, Carlo; Antal, Andrea; Siebner, Hartwig Roman; Ziemann, Ulf; Herrmann, Christoph S.

2017-01-01

Non-invasive transcranial brain stimulation (NTBS) techniques have a wide range of applications but also suffer from a number of limitations mainly related to poor specificity of intervention and variable effect size. These limitations motivated recent efforts to focus on the temporal dimension of NTBS with respect to the ongoing brain activity. Temporal patterns of ongoing neuronal activity, in particular brain oscillations and their fluctuations, can be traced with electro- or magnetoencephalography (EEG/MEG), to guide the timing as well as the stimulation settings of NTBS. These novel, online and offline EEG/MEG-guided NTBS-approaches are tailored to specifically interact with the underlying brain activity. Online EEG/MEG has been used to guide the timing of NTBS (i.e., when to stimulate): by taking into account instantaneous phase or power of oscillatory brain activity, NTBS can be aligned to fluctuations in excitability states. Moreover, offline EEG/MEG recordings prior to interventions can inform researchers and clinicians how to stimulate: by frequency-tuning NTBS to the oscillation of interest, intrinsic brain oscillations can be up- or down-regulated. In this paper, we provide an overview of existing approaches and ideas of EEG/MEG-guided interventions, and their promises and caveats. We point out potential future lines of research to address challenges. PMID:28233641

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

PubMed Central

Rossi, P. Justin; Gunduz, Aysegul; Judy, Jack; Wilson, Linda; Machado, Andre; Giordano, James J.; Elias, W. Jeff; Rossi, Marvin A.; Butson, Christopher L.; Fox, Michael D.; McIntyre, Cameron C.; Pouratian, Nader; Swann, Nicole C.; de Hemptinne, Coralie; Gross, Robert E.; Chizeck, Howard J.; Tagliati, Michele; Lozano, Andres M.; Goodman, Wayne; Langevin, Jean-Philippe; Alterman, Ron L.; Akbar, Umer; Gerhardt, Greg A.; Grill, Warren M.; Hallett, Mark; Herrington, Todd; Herron, Jeffrey; van Horne, Craig; Kopell, Brian H.; Lang, Anthony E.; Lungu, Codrin; Martinez-Ramirez, Daniel; Mogilner, Alon Y.; Molina, Rene; Opri, Enrico; Otto, Kevin J.; Oweiss, Karim G.; Pathak, Yagna; Shukla, Aparna; Shute, Jonathan; Sheth, Sameer A.; Shih, Ludy C.; Steinke, G. Karl; Tröster, Alexander I.; Vanegas, Nora; Zaghloul, Kareem A.; Cendejas-Zaragoza, Leopoldo; Verhagen, Leonard; Foote, Kelly D.; Okun, Michael S.

2016-01-01

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies. PMID:27092042

Sensor probes and phantoms for advanced transcranial magnetic stimulation system developments

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Patel, Prashil; Trivedi, Sudhir; Du, Xiaoming; Hong, Elliot; Choa, Fow-Sen

2015-05-01

Transcranial magnetic stimulation (TMS) has become one of the most widely used noninvasive method for brain tissue stimulation and has been used as a treatment tool for various neurological and psychiatric disorders including migraine, stroke, Parkinson's disease, dystonia, tinnitus and depression. In the process of developing advanced TMS deep brain stimulation tools, we need first to develop field measurement devices like sensory probes and brain phantoms, which can be used to calibrate the TMS systems. Currently there are commercially available DC magnetic or electric filed measurement sensors, but there is no instrument to measure transient fields. In our study, we used a commercial figure-8 shaped TMS coil to generate transient magnetic field and followed induced field and current. The coil was driven by power amplified signal from a pulse generator with tunable pulse rate, amplitude, and duration. In order to obtain a 3D plot of induced vector electric field, many types of probes were designed to detect single component of electric-field vectors along x, y and z axis in the space around TMS coil. We found that resistor probes has an optimized signal-to-noise ratio (SNR) near 3k ohm but it signal output is too weak compared with other techniques. We also found that inductor probes can have very high output for Curl E measurement, but it is not the E-field distribution we are interested in. Probes with electrical wire wrapped around iron coil can directly measure induced E-field with high sensitivity, which matched computer simulation results.

Decreased Peripheral and Central Responses to Acupuncture Stimulation following Modification of Body Ownership

PubMed Central

Chae, Younbyoung; Lee, In-Seon; Jung, Won-Mo; Chang, Dong-Seon; Napadow, Vitaly; Lee, Hyejung; Park, Hi-Joon; Wallraven, Christian

2014-01-01

Acupuncture stimulation increases local blood flow around the site of stimulation and induces signal changes in brain regions related to the body matrix. The rubber hand illusion (RHI) is an experimental paradigm that manipulates important aspects of bodily self-awareness. The present study aimed to investigate how modifications of body ownership using the RHI affect local blood flow and cerebral responses during acupuncture needle stimulation. During the RHI, acupuncture needle stimulation was applied to the real left hand while measuring blood microcirculation with a LASER Doppler imager (Experiment 1, N = 28) and concurrent brain signal changes using functional magnetic resonance imaging (fMRI; Experiment 2, N = 17). When the body ownership of participants was altered by the RHI, acupuncture stimulation resulted in a significantly lower increase in local blood flow (Experiment 1), and significantly less brain activation was detected in the right insula (Experiment 2). This study found changes in both local blood flow and brain responses during acupuncture needle stimulation following modification of body ownership. These findings suggest that physiological responses during acupuncture stimulation can be influenced by the modification of body ownership. PMID:25285620

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

PubMed

Löscher, Wolfgang; Cole, Andrew J; McLean, Michael J

2009-04-01

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

Frameless stereotaxy using bone fiducial markers for deep brain stimulation.

PubMed

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.

The neurophysiology of language: Insights from non-invasive brain stimulation in the healthy human brain.

PubMed

Hartwigsen, Gesa

2015-09-01

With the advent of non-invasive brain stimulation (NIBS), a new decade in the study of language has started. NIBS allows for testing the functional relevance of language-related brain activation and enables the researcher to investigate how neural activation changes in response to focal perturbations. This review focuses on the application of NIBS in the healthy brain. First, some basic mechanisms will be introduced and the prerequisites for carrying out NIBS studies of language are addressed. The next section outlines how NIBS can be used to characterize the contribution of the stimulated area to a task. In this context, novel approaches such as multifocal transcranial magnetic stimulation and the condition-and-perturb approach are discussed. The third part addresses the combination of NIBS and neuroimaging in the study of plasticity. These approaches are particularly suited to investigate short-term reorganization in the healthy brain and may inform models of language recovery in post-stroke aphasia. Copyright © 2014 The Author. Published by Elsevier Inc. All rights reserved.

Fiber-based tissue identification for electrode placement in deep brain stimulation neurosurgery (Conference Presentation)

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.

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

PubMed

Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R

2016-01-01

A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Noninvasive Brain Stimulation in Pediatric ADHD: A Review

PubMed Central

Rubio, Belen; Boes, Aaron D.; Laganiere, Simon; Rotenberg, Alexander; Jeurissen, Danique; Pascual-Leone, Alvaro

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in the pediatric population. The clinical management of ADHD is currently limited by a lack of reliable diagnostic biomarkers and inadequate therapy for a minority of patients that do not respond to standard pharmacotherapy. There is optimism that noninvasive brain stimulation may help to address these limitations. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two methods of noninvasive brain stimulation that modulate cortical excitability and brain network activity. TMS can be used diagnostically to probe cortical neurophysiology, while daily use of repetitive TMS or tDCS can induce long-lasting and potentially therapeutic changes in targeted networks. In this review we highlight research showing the potential diagnostic and therapeutic applications of TMS and tDCS in pediatric ADHD. We also discuss the safety and ethics of using these tools in the pediatric population. PMID:26661481

Brain lactate metabolism: the discoveries and the controversies

PubMed Central

Dienel, Gerald A

2012-01-01

Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an ‘opportunistic', glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. PMID:22186669

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields

PubMed Central

Ruffini, Giulio; Fox, Michael D.; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-01-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint of the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). PMID:24345389

Optimization of SSVEP brain responses with application to eight-command Brain-Computer Interface.

PubMed

Bakardjian, Hovagim; Tanaka, Toshihisa; Cichocki, Andrzej

2010-01-18

This study pursues the optimization of the brain responses to small reversing patterns in a Steady-State Visual Evoked Potentials (SSVEP) paradigm, which could be used to maximize the efficiency of applications such as Brain-Computer Interfaces (BCI). We investigated the SSVEP frequency response for 32 frequencies (5-84 Hz), and the time dynamics of the brain response at 8, 14 and 28 Hz, to aid the definition of the optimal neurophysiological parameters and to outline the onset-delay and other limitations of SSVEP stimuli in applications such as our previously described four-command BCI system. Our results showed that the 5.6-15.3 Hz pattern reversal stimulation evoked the strongest responses, peaking at 12 Hz, and exhibiting weaker local maxima at 28 and 42 Hz. After stimulation onset, the long-term SSVEP response was highly non-stationary and the dynamics, including the first peak, was frequency-dependent. The evaluation of the performance of a frequency-optimized eight-command BCI system with dynamic neurofeedback showed a mean success rate of 98%, and a time delay of 3.4s. Robust BCI performance was achieved by all subjects even when using numerous small patterns clustered very close to each other and moving rapidly in 2D space. These results emphasize the need for SSVEP applications to optimize not only the analysis algorithms but also the stimuli in order to maximize the brain responses they rely on. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Signal processing methods for reducing artifacts in microelectrode brain recordings caused by functional electrical stimulation

NASA Astrophysics Data System (ADS)

Young, D.; Willett, F.; Memberg, W. D.; Murphy, B.; Walter, B.; Sweet, J.; Miller, J.; Hochberg, L. R.; Kirsch, R. F.; Ajiboye, A. B.

2018-04-01

Objective. Functional electrical stimulation (FES) is a promising technology for restoring movement to paralyzed limbs. Intracortical brain-computer interfaces (iBCIs) have enabled intuitive control over virtual and robotic movements, and more recently over upper extremity FES neuroprostheses. However, electrical stimulation of muscles creates artifacts in intracortical microelectrode recordings that could degrade iBCI performance. Here, we investigate methods for reducing the cortically recorded artifacts that result from peripheral electrical stimulation. Approach. One participant in the BrainGate2 pilot clinical trial had two intracortical microelectrode arrays placed in the motor cortex, and thirty-six stimulating intramuscular electrodes placed in the muscles of the contralateral limb. We characterized intracortically recorded electrical artifacts during both intramuscular and surface stimulation. We compared the performance of three artifact reduction methods: blanking, common average reference (CAR) and linear regression reference (LRR), which creates channel-specific reference signals, composed of weighted sums of other channels. Main results. Electrical artifacts resulting from surface stimulation were 175  ×  larger than baseline neural recordings (which were 110 µV peak-to-peak), while intramuscular stimulation artifacts were only 4  ×  larger. The artifact waveforms were highly consistent across electrodes within each array. Application of LRR reduced artifact magnitudes to less than 10 µV and largely preserved the original neural feature values used for decoding. Unmitigated stimulation artifacts decreased iBCI decoding performance, but performance was almost completely recovered using LRR, which outperformed CAR and blanking and extracted useful neural information during stimulation artifact periods. Significance. The LRR method was effective at reducing electrical artifacts resulting from both intramuscular and surface FES, and almost completely restored iBCI decoding performance (>90% recovery for surface stimulation and full recovery for intramuscular stimulation). The results demonstrate that FES-induced artifacts can be easily mitigated in FES  +  iBCI systems by using LRR for artifact reduction, and suggest that the LRR method may also be useful in other noise reduction applications.

Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals

PubMed Central

Koos, Tibor; Buzsáki, György

2012-01-01

Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions. PMID:22496529

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

2001-06-01

Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology

PubMed Central

Michaud, Jean-Philippe; Hallé, Maxime; Lampron, Antoine; Thériault, Peter; Préfontaine, Paul; Filali, Mohammed; Tribout-Jover, Pascale; Lanteigne, Anne-Marie; Jodoin, Rachel; Cluff, Christopher; Brichard, Vincent; Palmantier, Rémi; Pilorget, Anthony; Larocque, Daniel; Rivest, Serge

2013-01-01

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aβ accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aβ may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APPswe/PS1 mice. MPL treatment led to a significant reduction in Aβ load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD. PMID:23322736

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

Nomura, S.; Enna, S.J.

Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar inmore » the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.« less

Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain's "operating system": how NAA metabolism supports meaningful intercellular frequency-encoded communications.

PubMed

Baslow, Morris H

2010-11-01

N-acetylaspartate (NAA), an acetylated derivative of L-aspartate (Asp), and N-acetylaspartylglutamate (NAAG), a derivative of NAA and L-glutamate (Glu), are synthesized by neurons in brain. However, neurons cannot catabolize either of these substances, and so their metabolism requires the participation of two other cell types. Neurons release both NAA and NAAG to extra-cellular fluid (ECF) upon stimulation, where astrocytes, the target cells for NAAG, hydrolyze it releasing NAA back into ECF, and oligodendrocytes, the target cells for NAA, hydrolyze it releasing Asp to ECF for recycling to neurons. This sequence is unique as it is the only known amino acid metabolic cycle in brain that requires three cell types for its completion. The results of this cycling are two-fold. First, neuronal metabolic water is transported to ECF for its removal from brain. Second, the rate of neuronal activity is coupled with focal hyperemia, providing stimulated neurons with the energy required for transmission of meaningful frequency-encoded messages. In this paper, it is proposed that the tri-cellular metabolism of NAA functions as the "operating system" of the brain, and is essential for normal cognitive and motor activities. Evidence in support of this hypothesis is provided by the outcomes of two human inborn errors in NAA metabolism.

Online Motor Imagery Training Effect for the Appearance of Event Related Desynchronization (ERD)

NASA Astrophysics Data System (ADS)

Takahashi, Mitsuru; Gouko, Manabu; Ito, Koji

Stroke patients have some motor deficits, but they can regain their motor abilities by rehabilitation. In the aspect of rehabilitation, voluntary movement is very important. We propose a system which can make a closed loop in brain for stroke patients like voluntary movement. Event Related Desynchronization (ERD) is used to extract patients' motor intention, and then Functional Electrical Stimulation (FES) stimuls their paralyzed muscles. In many Brain Computer Interface (BCI) researches, subjects are trained for several months or years to do the task, because of the difficulty to extract clear ERD without training. Thinking about applying for stroke patients, motor imagery training should be shorter, because of the brain plasticity. We did a pilot study about the effect of visual feedback training for three days with healthy subjects. The result indicated that ERD could be clearly extracted in three days, but the training effect differs in each subjects.

Therapeutic Effects of Caloric Stimulation and Optokinetic Stimulation on Hemispatial Neglect

PubMed Central

Moon, SY; Lee, BH

2006-01-01

Hemispatial neglect refers to a cognitive disorder in which patients with unilateral brain injury cannot recognize or respond to stimuli located in the contralesional hemispace. Hemispatial neglect in stroke patients is an important predictor for poor functional outcome. Therefore, there is a need for effective treatment for this condition. A number of interventions for hemispatial neglect have been proposed, although an approach resulting in persistent improvement is not available. Of these interventions, our review is focused on caloric stimulation and optokinetic stimulation. These lateralized or direction-specific stimulations of peripheral sensory systems can temporarily improve hemispatial neglect. According to recent functional MRI and PET studies, this improvement might result from the partial (re)activation of a distributed, multisensory vestibular network in the lesioned hemisphere, which is a part of a system that codes ego-centered space. However, much remain unknown regarding exact signal timing and directional selectivity of the network. PMID:20396481

Electrical stimulation as a means for achieving recovery of function in stroke patients.

PubMed

Popović, Dejan B; Sinkaer, Thomas; Popović, Mirjana B

2009-01-01

This review presents technologies used in and assesses the main clinical outcomes of electrical therapies designed to speed up and increase functional recovery in stroke patients. The review describes methods which interface peripheral systems (e.g., cyclic neural stimulation, stimulation triggered by electrical activity of muscles, therapeutic functional electrical stimulation) and transcranial brain stimulation with surface and implantable electrodes. Our conclusion from reviewing these data is that integration of electrical therapy into exercise-active movement mediated by electrical activation of peripheral and central sensory-motor mechanisms enhances motor re-learning following damage to the central nervous system. Motor re-learning is considered here as a set of processes associated with practice or experience that leads to long-term changes in the capability for movement. An important suggestion is that therapeutic effects are likely to be much more effective when treatment is applied in the acute, rather than in the chronic, phase of stroke.

Enhancing performance of a motor imagery based brain-computer interface by incorporating electrical stimulation-induced SSSEP

NASA Astrophysics Data System (ADS)

Yi, Weibo; Qiu, Shuang; Wang, Kun; Qi, Hongzhi; Zhao, Xin; He, Feng; Zhou, Peng; Yang, Jiajia; Ming, Dong

2017-04-01

Objective. We proposed a novel simultaneous hybrid brain-computer interface (BCI) by incorporating electrical stimulation into a motor imagery (MI) based BCI system. The goal of this study was to enhance the overall performance of an MI-based BCI. In addition, the brain oscillatory pattern in the hybrid task was also investigated. Approach. 64-channel electroencephalographic (EEG) data were recorded during MI, selective attention (SA) and hybrid tasks in fourteen healthy subjects. In the hybrid task, subjects performed MI with electrical stimulation which was applied to bilateral median nerve on wrists simultaneously. Main results. The hybrid task clearly presented additional steady-state somatosensory evoked potential (SSSEP) induced by electrical stimulation with MI-induced event-related desynchronization (ERD). By combining ERD and SSSEP features, the performance in the hybrid task was significantly better than in both MI and SA tasks, achieving a ~14% improvement in total relative to the MI task alone and reaching ~89% in mean classification accuracy. On the contrary, there was no significant enhancement obtained in performance while separate ERD feature was utilized in the hybrid task. In terms of the hybrid task, the performance using combined feature was significantly better than using separate ERD or SSSEP feature. Significance. The results in this work validate the feasibility of our proposed approach to form a novel MI-SSSEP hybrid BCI outperforming a conventional MI-based BCI through combing MI with electrical stimulation.

Electrical Stimulation of the Suprahyoid Muscles in Brain-injured Patients with Dysphagia: A Pilot Study

PubMed Central

Beom, Jaewon; Kim, Sang Jun

2011-01-01

Objective To investigate the therapeutic effects of repetitive electrical stimulation of the suprahyoid muscles in brain-injured patients with dysphagia. Method Twenty-eight brain-injured patients who showed reduced laryngeal elevation and supraglottic penetration or subglottic aspiration during a videofluoroscopic swallowing study (VFSS) were selected. The patients received either conventional dysphagia management (CDM) or CDM with repetitive electrical stimulation of the suprahyoid muscles (ESSM) for 4 weeks. The videofluoroscopic dysphagia scale (VDS) using the VFSS and American Speech-Language-Hearing Association National Outcome Measurement System (ASHA NOMS) swallowing scale (ASHA level) was used to determine swallowing function before and after treatment. Results VDS scores decreased from 29.8 to 17.9 in the ESSM group, and from 29.2 to 16.6 in the CDM group. However, there was no significant difference between the groups (p=0.796). Six patients (85.7%) in the ESSM group and 14 patients (66.7%) in the CDM group showed improvement according to the ASHA level with no significant difference between the ESSM and CDM groups (p=0.633). Conclusion Although repetitive neuromuscular electrical stimulation of the suprahyoid muscles did not further improve the swallowing function of dysphagia patients with reduced laryngeal elevation, more patients in the ESSM group showed improvement in the ASHA level than those in the CDM group. Further studies with concurrent controls and a larger sample group are required to fully establish the effects of repetitive neuromuscular electrical stimulation of the suprahyoid muscles in dysphagia patients. PMID:22506140

Methods of automated absence seizure detection, interference by stimulation, and possibilities for prediction in genetic absence models.

PubMed

van Luijtelaar, Gilles; Lüttjohann, Annika; Makarov, Vladimir V; Maksimenko, Vladimir A; Koronovskii, Alexei A; Hramov, Alexander E

2016-02-15

Genetic rat models for childhood absence epilepsy have become instrumental in developing theories on the origin of absence epilepsy, the evaluation of new and experimental treatments, as well as in developing new methods for automatic seizure detection, prediction, and/or interference of seizures. Various methods for automated off and on-line analyses of ECoG in rodent models are reviewed, as well as data on how to interfere with the spike-wave discharges by different types of invasive and non-invasive electrical, magnetic, and optical brain stimulation. Also a new method for seizure prediction is proposed. Many selective and specific methods for off- and on-line spike-wave discharge detection seem excellent, with possibilities to overcome the issue of individual differences. Moreover, electrical deep brain stimulation is rather effective in interrupting ongoing spike-wave discharges with low stimulation intensity. A network based method is proposed for absence seizures prediction with a high sensitivity but a low selectivity. Solutions that prevent false alarms, integrated in a closed loop brain stimulation system open the ways for experimental seizure control. The presence of preictal cursor activity detected with state of the art time frequency and network analyses shows that spike-wave discharges are not caused by sudden and abrupt transitions but that there are detectable dynamic events. Their changes in time-space-frequency characteristics might yield new options for seizure prediction and seizure control. Copyright © 2015 Elsevier B.V. All rights reserved.

Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System.

PubMed

Li, Dianyou; Zhang, Chencheng; Gault, Judith; Wang, Wei; Liu, Jianmin; Shao, Ming; Zhao, Yanyan; Zeljic, Kristina; Gao, Guodong; Sun, Bomin

2017-01-01

Deep brain stimulation (DBS) is the most commonly performed surgery for the debilitating symptoms of Parkinson disease (PD). However, DBS systems remain largely unaffordable to patients in developing countries, warranting the development of a safe, economically viable, and functionally comparable alternative. To investigate the efficacy and safety of wirelessly programmed DBS of bilateral subthalamic nucleus (STN) in patients with primary PD. Sixty-four patients with primary PD were randomly divided into test and control groups (1:1), where DBS was initiated at either 1 month or 3 months, respectively, after surgery. Safety and efficacy of the treatment were compared between on- and off-medication states 3 months after surgery. Outcome measures included analysis of Unified Parkinson's Disease Rating Scale (UPDRS) scores, duration of "on" periods, and daily equivalent doses of levodopa. All patients were followed up both 6 and 12 months after surgery. Three months after surgery, significant decrease in the UPDRS motor scores were observed for the test group in the off-medication state (25.08 ± 1.00) versus the control group (4.20 ± 1.99). Bilateral wireless programming STN-DBS is safe and effective for patients with primary PD in whom medical management has failed to restore motor function. © 2017 S. Karger AG, Basel.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

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 syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

PubMed

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.

Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

PubMed

Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

2012-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

Environmental Enrichment of Laboratory Rodents: The Answer Depends on the Question

DTIC Science & Technology

2011-01-01

that offer enhanced sensory , motor, and cognitive stimulation of brain neuronal systems in comparison with standard caging13 and, alternatively, as...benefit the animal in a signifi- cant way in terms of stimulation of positive species-typical behaviors and/or prevention of abnormal or undesirable...naturalistic nesting materials, as compared with less natural substitutes, al- lows laboratory mice to construct complex dome-shaped, multi - layered nests

"Sexy stimulants": the interaction between psychomotor stimulants and sexual behavior in the female brain.

PubMed

Guarraci, Fay A; Bolton, Jessica L

2014-06-01

Research indicates gender differences in sensitivity to psychomotor stimulants. Preclinical work investigating the interaction between drugs of abuse and sex-specific behaviors, such as sexual behavior, is critical to our understanding of such gender differences in humans. A number of behavioral paradigms can be used to model aspects of human sexual behavior in animal subjects. Although traditional assessment of the reflexive, lordosis posture of the female rat has been used to map the neuroanatomical and neurochemical systems that contribute to uniquely female copulatory behavior, the additional behavioral paradigms discussed in the current review have helped us expand our description of the appetitive and consummatory patterns of sexual behavior in the female rat. Measuring appetitive behavior is particularly important for assessing sexual motivation, the equivalent of "desire" in humans. By investigating the effects of commonly abused drugs on female sexual motivation, we are beginning to elucidate the role of dopaminergic neurotransmission, a neural system also known to be critical to the neurobiology of drug addiction, in female sexual motivation. A better understanding of the nexus of sex and drugs in the female brain will help advance our understanding of motivation in general and explain how psychomotor stimulants affect males and females differently. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

PubMed Central

Ackroff, Karen

2012-01-01

The discovery of taste and nutrient receptors (chemosensors) in the gut has led to intensive research on their functions. Whereas oral sugar, fat, and umami taste receptors stimulate nutrient appetite, these and other chemosensors in the gut have been linked to digestive, metabolic, and satiating effects that influence nutrient utilization and inhibit appetite. Gut chemosensors may have an additional function as well: to provide positive feedback signals that condition food preferences and stimulate appetite. The postoral stimulatory actions of nutrients are documented by flavor preference conditioning and appetite stimulation produced by gastric and intestinal infusions of carbohydrate, fat, and protein. Recent findings suggest an upper intestinal site of action, although postabsorptive nutrient actions may contribute to flavor preference learning. The gut chemosensors that generate nutrient conditioning signals remain to be identified; some have been excluded, including sweet (T1R3) and fatty acid (CD36) sensors. The gut-brain signaling pathways (neural, hormonal) are incompletely understood, although vagal afferents are implicated in glutamate conditioning but not carbohydrate or fat conditioning. Brain dopamine reward systems are involved in postoral carbohydrate and fat conditioning but less is known about the reward systems mediating protein/glutamate conditioning. Continued research on the postoral stimulatory actions of nutrients may enhance our understanding of human food preference learning. PMID:22442194

Myelin basic protein-messenger RNA (MBP-mRNA) expression during triethyltin-induced myelin edema.

PubMed

Veronesi, B; Jones, K; Gupta, S; Pringle, J; Mezei, C

1991-01-01

Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. TET has been reported to depress levels of myelin basic protein (MBP), a protein thought to play a critical role in myelin compaction. In the present study, the genomic expression (i.e., mRNA) of MBP was monitored throughout the pathogenesis of TET-induced myelin edema and recovery in Sprague-Dawley rats given a single injection of a neuropathic (8.0 mg/kg) or non-neuropathic (0.8 mg/kg) dose of TET-bromide. Levels of MBP-mRNA from the anterior and posterior brain were collected 1 hr, 3 hr, 2d, and 7d, postexposure. The optic nerve and caudal brainstem, representing anterior and posterior brain sites, respectively, were examined at the same time-points for ultrastructural evidence of edema and recovery. Our data indicate that neuropathic doses (8.0 mg/kg) of TET significantly stimulated MBP transcript throughout the brain at all exposure time-points. The magnitude and time-course of this stimulation differed in the anterior and posterior brain, with the latter region showing higher levels of MBP-mRNA. In the posterior brain, the highest levels of mRNA correlated with the appearance of edema in the caudal brainstem. In the anterior brain, MBP-mRNA levels were only marginally increased over controls. Ultrastructural evidence of myelin edema was confined to the brainstem in rats treated with neuropathic dose of TET. Intralamellar vacuolation appeared at 3 hr and 2d postexposure and could be correlated with peak levels of MBP transcript, whereas, recompacted myelin, which appeared by 7d postexposure, was associated with declining levels of the mRNA. Ultrastructural changes in the oligodendroglia were suggestive of metabolic stimulation and correlated with high MBP-mRNA levels. In summary, these data indicate that an initial genomic event in TET-induced myelin edema is stimulation of MBP transcript.

Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts

NASA Astrophysics Data System (ADS)

De Geeter, Nele; Dupré, Luc; Crevecoeur, Guillaume

2016-04-01

Objective. Transcranial magnetic stimulation (TMS) is a promising non-invasive tool for modulating the brain activity. Despite the widespread therapeutic and diagnostic use of TMS in neurology and psychiatry, its observed response remains hard to predict, limiting its further development and applications. Although the stimulation intensity is always maximum at the cortical surface near the coil, experiments reveal that TMS can affect deeper brain regions as well. Approach. The explanation of this spread might be found in the white matter fiber tracts, connecting cortical and subcortical structures. When applying an electric field on neurons, their membrane potential is altered. If this change is significant, more likely near the TMS coil, action potentials might be initiated and propagated along the fiber tracts towards deeper regions. In order to understand and apply TMS more effectively, it is important to capture and account for this interaction as accurately as possible. Therefore, we compute, next to the induced electric fields in the brain, the spatial distribution of the membrane potentials along the fiber tracts and its temporal dynamics. Main results. This paper introduces a computational TMS model in which electromagnetism and neurophysiology are combined. Realistic geometry and tissue anisotropy are included using magnetic resonance imaging and targeted white matter fiber tracts are traced using tractography based on diffusion tensor imaging. The position and orientation of the coil can directly be retrieved from the neuronavigation system. Incorporating these features warrants both patient- and case-specific results. Significance. The presented model gives insight in the activity propagation through the brain and can therefore explain the observed clinical responses to TMS and their inter- and/or intra-subject variability. We aspire to advance towards an accurate, flexible and personalized TMS model that helps to understand stimulation in the connected brain and to target more focused and deeper brain regions.

Effect of brain shift on the creation of functional atlases for deep brain stimulation surgery

PubMed Central

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) surgery has been demonstrated using intra-operative somatotopy recordings as well as stimulation response data. The results not only indicate that considerable brain shift happens before micro-electrode recordings in DBS but also that brain shift affects the creation of accurate functional atlases. Therefore, care must be taken when building and using such atlases of intra-operative data and also when using intra-operative data to validate anatomical atlases. PMID:20033503

Models to Tailor Brain Stimulation Therapies in Stroke

PubMed Central

Plow, E. B.; Sankarasubramanian, V.; Cunningham, D. A.; Potter-Baker, K.; Varnerin, N.; Cohen, L. G.; Sterr, A.; Conforto, A. B.; Machado, A. G.

2016-01-01

A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke. PMID:27006833

Interactions between the Central Nervous System and Pancreatic Islet Secretions: A Historical Perspective

ERIC Educational Resources Information Center

Begg, Denovan P.; Woods, Stephen C.

2013-01-01

The endocrine pancreas is richly innervated with sympathetic and parasympathetic projections from the brain. In the mid-20th century, it was established that alpha-adrenergic activation inhibits, whereas cholinergic stimulation promotes, insulin secretion; this demonstrated the importance of the sympathetic and parasympathetic systems in…

Activation of Phosphoinositide Metabolism by Cholinergic Agents.

DTIC Science & Technology

1992-03-15

most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

Portable wireless electrocorticography system with a flexible microelectrodes array for epilepsy treatment.

PubMed

Xie, Kejun; Zhang, Shaomin; Dong, Shurong; Li, Shijian; Yu, Chaonan; Xu, Kedi; Chen, Wanke; Guo, Wei; Luo, Jikui; Wu, Zhaohui

2017-08-10

In this paper, we present a portable wireless electrocorticography (ECoG) system. It uses a high resolution 32-channel flexible ECoG electrodes array to collect electrical signals of brain activities and to stimulate the lesions. Electronic circuits are designed for signal acquisition, processing and transmission using Bluetooth Low Energy 4 (LTE4) for wireless communication with cell phone. In-vivo experiments on a rat show that the flexible ECoG system can accurately record electrical signals of brain activities and transmit them to cell phone with a maximal sampling rate of 30 ksampling/s per channel. It demonstrates that the epilepsy lesions can be detected, located and treated through the ECoG system. The wireless ECoG system has low energy consumption and high brain spatial resolution, thus has great prospects for future application.

Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

PubMed

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.

Essential Tremor

MedlinePlus

... individuals. Deep brain stimulation uses a surgically implanted, battery-operated medical device called a neurostimulator to delivery ... individuals. Deep brain stimulation uses a surgically implanted, battery-operated medical device called a neurostimulator to delivery ...

[Obsessive-compulsive disorder, a new model of basal ganglia dysfunction? Elements from deep brain stimulation studies].

PubMed

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.

Regional anatomy of the pedunculopontine nucleus: relevance for deep brain stimulation.

PubMed

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.

Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study.

PubMed

Choi, Gyu-Sik; Kwak, Sang Gyu; Lee, Han Do; Chang, Min Cheol

2018-02-28

Central pain can occur following traumatic brain injury, leading to poor functional recovery, limitation of activities of daily living, and decreased quality of life. The aim of this study was to determine whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation, applied over the primary motor cortex of the affected hemisphere, can be used to manage chronic central pain after mild traumatic brain injury. Prospective randomized feasibility study. Twelve patients with mild traumatic brain injury and chronic central pain were randomly assigned to transcranial magnetic stimulation (high-frequency stimulation, 10 sessions) or sham groups. Diffuse tensor tractography revealed partially injured spinothalamocortical tracts in all recruited patients. A numerical rating scale (NRS) was used to evaluate pain intensity during pre-treatment and immediately after the 5th transcranial magnetic stimulation session (post1), 10th transcranial magnetic stimulation session (post2), and 1 (post3), 2 (post4), and 4 weeks (post 5) after finishing treatment. Physical and mental health status were evaluated using the Short Form 36 Health Survey (SF-36), including physical and mental component scores (PCS, MCS). The NRS score of the repetitive transcranial magnetic stimulation group was significantly lower than the sham group score at all clinical evaluation time-points during and after transcranial magnetic stimulation sessions. The transcranial magnetic stimulation group's SF-36 PCS score was significantly higher at post2, post3, post4, and post5 compared with the sham group. High-frequency transcranial magnetic stimulation may be used to manage chronic central pain and improve quality of life in patients with mild traumatic brain injury. However, this is a pilot study and further research is needed.

Brain networks modulated by subthalamic nucleus deep brain stimulation.

PubMed

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 Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The development and modeling of devices and paradigms for transcranial magnetic stimulation

PubMed Central

Goetz, Stefan M.; Deng, Zhi-De

2017-01-01

Magnetic stimulation is a noninvasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modeling. PMID:28443696

Novel transcranial magnetic stimulation coil for mice

NASA Astrophysics Data System (ADS)

March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

2014-03-01

Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

Brain-controlled muscle stimulation for the restoration of motor function

PubMed Central

Ethier, Christian; Miller, Lee E

2014-01-01

Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional Electrical Stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these ‘Brain Machine Interfaces’ (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. PMID:25447224

The development and modelling of devices and paradigms for transcranial magnetic stimulation.

PubMed

Goetz, Stefan M; Deng, Zhi-De

2017-04-01

Magnetic stimulation is a non-invasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain, as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modelling.

Testing for a "sobering pill"

DOT National Transportation Integrated Search

1974-12-01

The concept of blocking or neutralizing the effect of alcohol on the brain was investigated in a series of human tests. It was found that pharmacological agents which stimulate the dopaminergic system tend to neutralize the alcohol reduced performanc...

Alternative surgical approaches in epilepsy.

PubMed

Gigante, Paul R; Goodman, Robert R

2011-08-01

The mainstay of epilepsy surgery is the resection of a presumed seizure focus or disruption of seizure propagation pathways. These approaches cannot be applied to all patients with medically refractory epilepsy (MRE). Since 1997, vagus nerve stimulation has been a palliative adjunct to the care of MRE patients. Deep brain stimulation (DBS) in select locations has been reported to reduce seizure frequency in small studies over the past three decades. Recently published results from the SANTE (Stimulation of the Anterior Nuclei of Thalamus for Epilepsy) trial-the first large-scale, randomized, double-blind trial of bilateral anterior thalamus DBS for MRE-demonstrate a significant reduction in seizure frequency with programmed stimulation. Another surgical alternative is the RNS™ System (NeuroPace, Mountain View, CA), which uses a closed-loop system termed responsive neurostimulation to both detect apparent seizure onsets and deliver stimulation. Recently presented results from the RNS™ pivotal trial demonstrate a sustained reduction in seizure frequency with stimulation, although comprehensive trial results are pending.

Dopamine D3 receptor antagonism inhibits cocaine-seeking and cocaine-enhanced brain reward in rats.

PubMed

Vorel, Stanislav R; Ashby, Charles R; Paul, Mousumi; Liu, Xinhe; Hayes, Robert; Hagan, Jim J; Middlemiss, Derek N; Stemp, Geoffrey; Gardner, Eliot L

2002-11-01

dopamine D3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.

Brain Inositol Is a Novel Stimulator for Promoting Cryptococcus Penetration of the Blood-Brain Barrier

PubMed Central

Wang, Yina; Toffaletti, Dena L.; Eugenin, Eliseo; Perfect, John R.; Kim, Kee Jun; Xue, Chaoyang

2013-01-01

Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. The facts that human and animal brains contain abundant inositol and that Cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. In this study, we found that inositol plays an important role in Cryptococcus traversal across the blood-brain barrier (BBB) both in an in vitro human BBB model and in in vivo animal models. The capacity of inositol to stimulate BBB crossing was dependent upon fungal inositol transporters, indicated by a 70% reduction in transmigration efficiency in mutant strains lacking two major inositol transporters, Itr1a and Itr3c. Upregulation of genes involved in the inositol catabolic pathway was evident in a microarray analysis following inositol treatment. In addition, inositol increased the production of hyaluronic acid in Cryptococcus cells, which is a ligand known to binding host CD44 receptor for their invasion. These studies suggest an inositol-dependent Cryptococcus traversal of the BBB, and support our hypothesis that utilization of host-derived inositol by Cryptococcus contributes to CNS infection. PMID:23592982

Low tryptophan diet decreases brain serotonin and alters response to apomorphine

NASA Technical Reports Server (NTRS)

Sahakian, B. J.; Wurtman, R. J.; Barr, J. K.; Millington, W. R.; Chiel, H. J.

1979-01-01

The role of the serotoninergic system in the regulation of apomorphine-induced behavior, a behavior primarily controlled by dopaminergic neurotransmission, was investigated in rats fed on a low tryptophan diet since weaning. It was found that reductions in brain seritonin (5-HT) produced by diet result in decreased stereotypy after apomorphine administration. This indicates that although stereotyped behavior is primarily mediated by dopaminergic mechanisms, it can also be modulated by other neurotransmitter including 5-HT. It was also shown that changes in brain seritonin levels can affect psychomotor stimulant-induced hypothermia.

Lasting EEG/MEG Aftereffects of Rhythmic Transcranial Brain Stimulation: Level of Control Over Oscillatory Network Activity

PubMed Central

Veniero, Domenica; Vossen, Alexandra; Gross, Joachim; Thut, Gregor

2015-01-01

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS), and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity (“frequency-tuning”). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e., online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity. PMID:26696834

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

PubMed

Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

2014-04-01

Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.

PubMed

Moro, Elena; Hamani, Clement; Poon, Yu-Yan; Al-Khairallah, Thamar; Dostrovsky, Jonathan O; Hutchison, William D; Lozano, Andres M

2010-01-01

Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.

Transcranial magnetic stimulation of the left dorsolateral prefrontal cortex decreases cue-induced nicotine craving and EEG delta power.

PubMed

Pripfl, Jürgen; Tomova, Livia; Riecansky, Igor; Lamm, Claus

2014-01-01

TMS has high potential as smoking cessation treatment. However, the neural mechanisms underlying TMS induced reduction of tobacco craving remain unclear. Electroencephalographic (EEG) delta frequency has been associated with the activity of the dopaminergic brain reward system, which is crucial for nicotine induced effects, and decreases after nicotine admission in smokers. The aim of this study was to investigate EEG delta power changes induced by hf rTMS of the left dorsolateral prefrontal cortex (DLPFC) in nicotine deprived smokers and it's relation to cue-induced nicotine craving. Fourteen healthy smokers meeting ICD-10 criteria for tobacco addiction participated in this within-subject sham controlled study. Participants had to abstain from smoking 6 h before the experiment. Effects of high-frequency repetitive TMS (hf rTMS) (10 Hz) for verum (left DLPFC) and sham (vertex) stimulations on cue-induced nicotine craving and resting state EEG delta power were assessed before and three times within 40 min after rTMS. Both craving (P = 0.046) and EEG delta power (P = 0.048) were significantly lower after verum stimulation compared to sham stimulation across the whole post stimulation time period assessed. However, changes of craving ratings and delta power did not correlate. Hf rTMS applied to the left DLPFC reduces nicotine craving in short-term abstinent smokers. Changes in delta activity support the idea that stimulation induced effects are mediated by the dopaminergic brain reward system, which presumably plays a prominent, but probably not exclusive, role in this stimulation induced behavioral modulation, making this method a promising smoking cessation treatment candidate. Copyright © 2014 Elsevier Inc. All rights reserved.

Did I Do That? Expectancy Effects of Brain Stimulation on Error-related Negativity and Sense of Agency.

PubMed

Hoogeveen, Suzanne; Schjoedt, Uffe; van Elk, Michiel

2018-06-19

This study examines the effects of expected transcranial stimulation on the error(-related) negativity (Ne or ERN) and the sense of agency in participants who perform a cognitive control task. Placebo transcranial direct current stimulation was used to elicit expectations of transcranially induced cognitive improvement or impairment. The improvement/impairment manipulation affected both the Ne/ERN and the sense of agency (i.e., whether participants attributed errors to oneself or the brain stimulation device): Expected improvement increased the ERN in response to errors compared with both impairment and control conditions. Expected impairment made participants falsely attribute errors to the transcranial stimulation. This decrease in sense of agency was correlated with a reduced ERN amplitude. These results show that expectations about transcranial stimulation impact users' neural response to self-generated errors and the attribution of responsibility-especially when actions lead to negative outcomes. We discuss our findings in relation to predictive processing theory according to which the effect of prior expectations on the ERN reflects the brain's attempt to generate predictive models of incoming information. By demonstrating that induced expectations about transcranial stimulation can have effects at a neural level, that is, beyond mere demand characteristics, our findings highlight the potential for placebo brain stimulation as a promising tool for research.

Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

PubMed

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.

Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.

PubMed

Mandonnet, Emmanuel; Winkler, Peter A; Duffau, Hugues

2010-02-01

While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

Model-based iterative learning control of Parkinsonian state in thalamic relay neuron

NASA Astrophysics Data System (ADS)

Liu, Chen; Wang, Jiang; Li, Huiyan; Xue, Zhiqin; Deng, Bin; Wei, Xile

2014-09-01

Although the beneficial effects of chronic deep brain stimulation on Parkinson's disease motor symptoms are now largely confirmed, the underlying mechanisms behind deep brain stimulation remain unclear and under debate. Hence, the selection of stimulation parameters is full of challenges. Additionally, due to the complexity of neural system, together with omnipresent noises, the accurate model of thalamic relay neuron is unknown. Thus, the iterative learning control of the thalamic relay neuron's Parkinsonian state based on various variables is presented. Combining the iterative learning control with typical proportional-integral control algorithm, a novel and efficient control strategy is proposed, which does not require any particular knowledge on the detailed physiological characteristics of cortico-basal ganglia-thalamocortical loop and can automatically adjust the stimulation parameters. Simulation results demonstrate the feasibility of the proposed control strategy to restore the fidelity of thalamic relay in the Parkinsonian condition. Furthermore, through changing the important parameter—the maximum ionic conductance densities of low-threshold calcium current, the dominant characteristic of the proposed method which is independent of the accurate model can be further verified.

Neuromodulation: Selected approaches and challenges

PubMed Central

Parpura, Vladimir; Silva, Gabriel A.; Tass, Peter A.; Bennet, Kevin E.; Meyyappan, Meyya; Koehne, Jessica; Lee, Kendall H.; Andrews, Russell J.

2012-01-01

The brain operates through complex interactions in the flow of information and signal processing within neural networks. The “wiring” of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing “misfiring” neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. PMID:23190025

Bimanual Force Coordination in Parkinson’s Disease Patients with Bilateral Subthalamic Deep Brain Stimulation

PubMed Central

Gorniak, Stacey L.; McIntyre, Cameron C.; Alberts, Jay L.

2013-01-01

Objective Studies of bimanual actions similar to activities of daily living (ADLs) are currently lacking in evaluating fine motor control in Parkinson’s disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS) patients. Methods Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition. Results The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition. Conclusion While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination. PMID:24244388

Food consumption increases cell proliferation in the python brain.

PubMed

Habroun, Stacy S; Schaffner, Andrew A; Taylor, Emily N; Strand, Christine R

2018-04-06

Pythons are model organisms for investigating physiological responses to food intake. While systemic growth in response to food consumption is well documented, what occurs in the brain is currently unexplored. In this study, male ball pythons ( Python regius ) were used to test the hypothesis that food consumption stimulates cell proliferation in the brain. We used 5-bromo-12'-deoxyuridine (BrdU) as a cell-birth marker to quantify and compare cell proliferation in the brain of fasted snakes and those at 2 and 6 days after a meal. Throughout the telencephalon, cell proliferation was significantly increased in the 6 day group, with no difference between the 2 day group and controls. Systemic postprandial plasticity occurs quickly after a meal is ingested, during the period of active digestion; however, the brain displays a surge of cell proliferation after most digestion and absorption is complete. © 2018. Published by The Company of Biologists Ltd.

Characteristics of bowl-shaped coils for transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Yamamoto, Keita; Suyama, Momoko; Takiyama, Yoshihiro; Kim, Dongmin; Saitoh, Youichi; Sekino, Masaki

2015-05-01

Transcranial magnetic stimulation (TMS) has recently been used as a method for the treatment of neurological and psychiatric diseases. Daily TMS sessions can provide continuous therapeutic effectiveness, and the installation of TMS systems at patients' homes has been proposed. A figure-eight coil, which is normally used for TMS therapy, induces a highly localized electric field; however, it is challenging to achieve accurate coil positioning above the targeted brain area using this coil. In this paper, a bowl-shaped coil for stimulating a localized but wider area of the brain is proposed. The coil's electromagnetic characteristics were analyzed using finite element methods, and the analysis showed that the bowl-shaped coil induced electric fields in a wider area of the brain model than a figure-eight coil. The expanded distribution of the electric field led to greater robustness of the coil to the coil-positioning error. To improve the efficiency of the coil, the relationship between individual coil design parameters and the resulting coil characteristics was numerically analyzed. It was concluded that lengthening the outer spherical radius and narrowing the width of the coil were effective methods for obtaining a more effective and more uniform distribution of the electric field.

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.

Précis of The brain and emotion.

PubMed

Rolls, E T

2000-04-01

The topics treated in The brain and emotion include the definition, nature, and functions of emotion (Ch. 3); the neural bases of emotion (Ch. 4); reward, punishment, and emotion in brain design (Ch. 10); a theory of consciousness and its application to understanding emotion and pleasure (Ch. 9); and neural networks and emotion-related learning (Appendix). The approach is that emotions can be considered as states elicited by reinforcers (rewards and punishers). This approach helps with understanding the functions of emotion, with classifying different emotions, and in understanding what information-processing systems in the brain are involved in emotion, and how they are involved. The hypothesis is developed that brains are designed around reward- and punishment-evaluation systems, because this is the way that genes can build a complex system that will produce appropriate but flexible behavior to increase fitness (Ch. 10). By specifying goals rather than particular behavioral patterns of responses, genes leave much more open the possible behavioral strategies that might be required to increase fitness. The importance of reward and punishment systems in brain design also provides a basis for understanding the brain mechanisms of motivation, as described in Chapters 2 for appetite and feeding, 5 for brain-stimulation reward, 6 for addiction, 7 for thirst, and 8 for sexual behavior.

Effects of brain-computer interface-based functional electrical stimulation on brain activation in stroke patients: a pilot randomized controlled trial.

PubMed

Chung, EunJung; Kim, Jung-Hee; Park, Dae-Sung; Lee, Byoung-Hee

2015-03-01

[Purpose] This study sought to determine the effects of brain-computer interface-based functional electrical stimulation (BCI-FES) on brain activation in patients with stroke. [Subjects] The subjects were randomized to in a BCI-FES group (n=5) and a functional electrical stimulation (FES) group (n=5). [Methods] Patients in the BCI-FES group received ankle dorsiflexion training with FES for 30 minutes per day, 5 times under the brain-computer interface-based program. The FES group received ankle dorsiflexion training with FES for the same amount of time. [Results] The BCI-FES group demonstrated significant differences in the frontopolar regions 1 and 2 attention indexes, and frontopolar 1 activation index. The FES group demonstrated no significant differences. There were significant differences in the frontopolar 1 region activation index between the two groups after the interventions. [Conclusion] The results of this study suggest that BCI-FES training may be more effective in stimulating brain activation than only FES training in patients recovering from stroke.

Characterization of EEG patterns in brain-injured subjects and controls after a Snoezelen(®) intervention.

PubMed

Gómez, Carlos; Poza, Jesús; Gutiérrez, María T; Prada, Esther; Mendoza, Nuria; Hornero, Roberto

2016-11-01

The aim of this study was to assess the changes induced in electroencephalographic (EEG) activity by a Snoezelen(®) intervention on individuals with brain-injury and control subjects. EEG activity was recorded preceding and following a Snoezelen(®) session in 18 people with cerebral palsy (CP), 18 subjects who have sustained traumatic brain-injury (TBI) and 18 controls. EEG data were analyzed by means of spectral and nonlinear measures: median frequency (MF), individual alpha frequency (IAF), sample entropy (SampEn) and Lempel-Ziv complexity (LZC). Our results showed decreased values for MF, IAF, SampEn and LZC as a consequence of the therapy. The main changes between pre-stimulation and post-stimulation conditions were found in occipital and parietal brain areas. Additionally, these changes are more widespread in controls than in brain-injured subjects, which can be due to cognitive deficits in TBI and CP groups. Our findings support the notion that Snoezelen(®) therapy affects central nervous system, inducing a slowing of oscillatory activity, as well as a decrease of EEG complexity and irregularity. These alterations seem to be related with higher levels of relaxation of the participants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of Parkinson's Disease in Transcranial Magnetic Stimulation Treatment

NASA Astrophysics Data System (ADS)

Syeda, Farheen; Magsood, Hamzah; Lee, Erik; El-Gendy, Ahmed; Jiles, David; Hadimani, Ravi

Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

Nanoparticles: A Challenging Vehicle for Neural Stimulation

PubMed Central

Colombo, Elisabetta; Feyen, Paul; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio

2016-01-01

Neurostimulation represents a powerful and well-established tool for the treatment of several diseases affecting the central nervous system. Although, effective in reducing the symptoms or the progression of brain disorders, the poor accessibility of the deepest areas of the brain currently hampers the possibility of a more specific and controlled therapeutic stimulation, depending on invasive surgical approaches and long-term stability, and biocompatibility issues. The massive research of the last decades on nanomaterials and nanoscale devices favored the development of new tools to address the limitations of the available neurostimulation approaches. This mini-review focuses on the employment of nanoparticles for the modulation of the electrophysiological activity of neuronal networks and the related transduction mechanisms underlying the nanostructure-neuron interfaces. PMID:27047327

Noninvasive Brain Stimulation and Personal Identity: Ethical Considerations

PubMed Central

Iwry, Jonathan; Yaden, David B.; Newberg, Andrew B.

2017-01-01

As noninvasive brain stimulation (NIBS) technology advances, these methods may become increasingly capable of influencing complex networks of mental functioning. We suggest that these might include cognitive and affective processes underlying personality and belief systems, which would raise important questions concerning personal identity and autonomy. We give particular attention to the relationship between personal identity and belief, emphasizing the importance of respecting users' personal values. We posit that research participants and patients should be encouraged to take an active approach to considering the personal implications of altering their own cognition, particularly in cases of neurocognitive “enhancement.” We suggest that efforts to encourage careful consideration through the informed consent process would contribute usefully to studies and treatments that use NIBS. PMID:28638327

Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks.

PubMed

Hallett, Mark; Di Iorio, Riccardo; Rossini, Paolo Maria; Park, Jung E; Chen, Robert; Celnik, Pablo; Strafella, Antonio P; Matsumoto, Hideyuki; Ugawa, Yoshikazu

2017-11-01

The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain. Published by Elsevier B.V.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2014-09-01

810. 22. Plow EB, Carey JR, Nudo RJ, Pascual-Leone A (2009) Invasive cortical stimulation to promote recovery of function after stroke: A critical...stimulation of the motor cortex enhances pro- genitor cell migration in the adult rat brain. Exp Brain Res 231(2):165–177. 28. Edwardson MA, Lucas TH, Carey ...The screws and rod were further secured with dental acrylic (all animals). In both the ADS and OLS groups, a hybrid, 16-channel, single-shank, chronic

Both anodal and cathodal transcranial direct current stimulation improves semantic processing.

PubMed

Brückner, Sabrina; Kammer, Thomas

2017-02-20

Transcranial direct current stimulation (tDCS) is a common method to modulate cortical activity. Anodal tDCS is usually associated with an enhancement of the stimulated brain area, whereas cathodal tDCS is often described as inhibitory brain stimulation method. Our aim was to investigate whether this canonical assumption derived from the motor system could be transferred to the semantic system. Three groups with 20 healthy subjects each were stimulated at Wernicke's area with either anodal, cathodal or sham tDCS. Subsequently, they performed a simple lexical decision task for a duration of about 25min. Subjects receiving anodal tDCS revealed faster reaction times (RTs) compared to the sham group, although not reaching statistical significance. Surprisingly, in the cathodal group RTs were decreased significantly. All subjects were faster in the second half of the task, but the tDCS-induced improvement lasted for the entire duration of the task. Error rates were not influenced by tDCS, neither were RTs in a choice reaction time task. Thus, both anodal and cathodal tDCS applied to Wernicke's area improved semantic processing. Recently, a meta-analysis revealed that the canonical anodal excitation and cathodal inhibition assumption is observed rarely in cognitive studies. In particular, an inhibitory effect of cathodal tDCS on cognition is rare. Our findings thus support the speculation, that especially language functions could be somewhat 'immune' to cathodal inhibition. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Neurotherapy of Traumatic Brain Injury/Post-Traumatic Stress Symptoms in Vietnam Veterans.

PubMed

Nelson, David V; Esty, Mary Lee

2015-10-01

Previous report suggested the beneficial effects of an adaptation of the Flexyx Neurotherapy System (FNS) for the amelioration of mixed traumatic brain injury/post-traumatic stress symptoms in veterans of the Afghanistan and Iraq wars. As a novel variant of electroencephalograph biofeedback, FNS falls within the bioenergy domain of complementary and alternative medicine. Rather than learning voluntary control over the production/inhibition of brain wave patterns, FNS involves offsetting stimulation of brain wave activity by means of an external energy source, specifically, the conduction of electromagnetic energy stimulation via the connecting electroencephalograph cables. Essentially, these procedures subliminally induce strategic distortion of ongoing brain wave activity to presumably facilitate resetting of more adaptive patterns of activity. Reported herein are two cases of Vietnam veterans with mixed traumatic brain injury/post-traumatic stress symptoms, each treated with FNS for 25 sessions. Comparisons of pre- and post-treatment questionnaire assessments revealed notable decreases for all symptoms, suggesting improvements across the broad domains of cognition, pain, sleep, fatigue, and mood/emotion, including post-traumatic stress symptoms, as well as for overall activity levels. Findings suggest FNS treatment may be of potential benefit for the partial amelioration of symptoms, even in some individuals for whom symptoms have been present for decades. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Limiting glioma development by photodynamic therapy-generated macrophage vaccine and allo-stimulation: an in vivo histological study in rats

NASA Astrophysics Data System (ADS)

Madsen, Steen J.; Christie, Catherine; Huynh, Khoi; Peng, Qian; Uzal, Francisco A.; Krasieva, Tatiana B.; Hirschberg, Henry

2018-02-01

Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage (MaF98) vaccines can be increased by: (1) photodynamic therapy (PDT) of the priming tumor cells and (2) intracranial injection of allogeneic glioma cells directly into the tumor site. Experiments were conducted in an in vivo brain tumor development model using Fischer rats and F98 (syngeneic) and BT4C (allogeneic) glioma cells. The results showed that immunization with Ma (acting as antigen-presenting cells), primed with PDT-treated tumor cells (MaF98), significantly slowed but did not prevent the growth of F98-induced tumors in the brain. Complete suppression of tumor development was obtained via MaF98 inoculation combined with direct intracranial injection of allogeneic glioma cells. No deleterious effects were noted in any of the animals during the 14-day observation period.

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

PubMed

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Transcranial direct current stimulation and power spectral parameters: a tDCS/EEG co-registration study

PubMed Central

Mangia, Anna L.; Pirini, Marco; Cappello, Angelo

2014-01-01

Transcranial direct current stimulation (tDCS) delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG) monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta, and gamma power bands were investigated. Three main findings emerged: (1) an increase in theta band activity during the first minutes of stimulation; (2) an increase in alpha and beta power during and after stimulation; (3) a widespread activation in several brain regions. PMID:25147519

Pathways of translation: deep brain stimulation.

PubMed

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.

[Emotion and basal ganglia (II): what can we learn from subthalamic nucleus deep brain stimulation in Parkinson's disease?].

PubMed

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.

Mood stability in Parkinson disease following deep brain stimulation: a 6-month prospective follow-up study.

PubMed

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.

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury

PubMed Central

Grau, James W.; Huie, J. Russell; Lee, Kuan H.; Hoy, Kevin C.; Huang, Yung-Jen; Turtle, Joel D.; Strain, Misty M.; Baumbauer, Kyle M.; Miranda, Rajesh M.; Hook, Michelle A.; Ferguson, Adam R.; Garraway, Sandra M.

2014-01-01

Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl- concentrations increase (due to a down-regulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition. PMID:25249941

Prenatal Stress and Peripubertal Stimulation of the Endocannabinoid System Differentially Regulate Emotional Responses and Brain Metabolism in Mice

PubMed Central

Macrì, Simone; Ceci, Chiara; Canese, Rossella; Laviola, Giovanni

2012-01-01

The central endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal-axis mediate individual responses to emotionally salient stimuli. Their altered developmental adjustment may relate to the emergence of emotional disturbances. Although environmental influences regulate the individual phenotype throughout the entire lifespan, their effects may result particularly persistent during plastic developmental stages (e.g. prenatal life and adolescence). Here, we investigated whether prenatal stress – in the form of gestational exposure to corticosterone supplemented in the maternal drinking water (100 mg/l) during the last week of pregnancy – combined with a pharmacological stimulation of the ECS during adolescence (daily fatty acid amide hydrolase URB597 i.p. administration - 0.4 mg/kg - between postnatal days 29–38), influenced adult mouse emotional behaviour and brain metabolism measured through in vivo quantitative magnetic resonance spectroscopy. Compared to control mice, URB597-treated subjects showed, in the short-term, reduced locomotion and, in the long term, reduced motivation to execute operant responses to obtain palatable rewards paralleled by reduced levels of inositol and taurine in the prefrontal cortex. Adult mice exposed to prenatal corticosterone showed increased behavioural anxiety and reduced locomotion in the elevated zero maze, and altered brain metabolism (increased glutamate and reduced taurine in the hippocampus; reduced inositol and N-Acetyl-Aspartate in the hypothalamus). Present data further corroborate the view that prenatal stress and pharmacological ECS stimulation during adolescence persistently regulate emotional responses in adulthood. Yet, whilst we hypothesized these factors to be interactive in nature, we observed that the consequences of prenatal corticosterone administration were independent from those of ECS drug-induced stimulation during adolescence. PMID:22848620

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

PubMed Central

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

2010-01-01

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

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures

PubMed Central

Weiss, Tali; Shushan, Sagit; Ravia, Aharon; Hahamy, Avital; Secundo, Lavi; Weissbrod, Aharon; Ben-Yakov, Aya; Holtzman, Yael; Cohen-Atsmoni, Smadar; Roth, Yehudah; Sobel, Noam

2016-01-01

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose. PMID:27591145

Virtual reality adaptive stimulation of limbic networks in the mental readiness training.

PubMed

Cosić, Kresimir; Popović, Sinisa; Kostović, Ivica; Judas, Milos

2010-01-01

A significant proportion of severe psychological problems in recent large-scale peacekeeping operations underscores the importance of effective methods for strengthening the stress resilience. Virtual reality (VR) adaptive stimulation, based on the estimation of the participant's emotional state from physiological signals, may enhance the mental readiness training (MRT). Understanding neurobiological mechanisms by which the MRT based on VR adaptive stimulation can affect the resilience to stress is important for practical application in the stress resilience management. After the delivery of a traumatic audio-visual stimulus in the VR, the cascade of events occurs in the brain, which evokes various physiological manifestations. In addition to the "limbic" emotional and visceral brain circuitry, other large-scale sensory, cognitive, and memory brain networks participate with less known impact in this physiological response. The MRT based on VR adaptive stimulation may strengthen the stress resilience through targeted brain-body interactions. Integrated interdisciplinary efforts, which would integrate the brain imaging and the proposed approach, may contribute to clarifying the neurobiological foundation of the resilience to stress.

BDNF and AMPA receptors in the cNTS modulate the hyperglycemic reflex after local carotid body NaCN stimulation.

PubMed

Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Melnikov, V; Virgen-Ortiz, A; Lemus, M; Pineda-Lemus, M; de Álvarez-Buylla, E

2017-07-01

The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation. Copyright © 2017. Published by Elsevier B.V.

Electrical Stimulation in Hippocampus and Entorhinal Cortex Impairs Spatial and Temporal Memory.

PubMed

Goyal, Abhinav; Miller, Jonathan; Watrous, Andrew J; Lee, Sang Ah; Coffey, Tom; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn A; Inman, Cory; Sheth, Sameer A; Wanda, Paul A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Jacobs, Joshua

2018-05-09

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory. Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.

Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

PubMed Central

Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

2011-01-01

OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

Neural stimulation for Parkinson's disease: current therapies and future directions.

PubMed

Neimat, Joseph S; Hamani, Clement; Lozano, Andres M

2006-01-01

Neural stimulation has rapidly become an integral tool in the treatment of Parkinson's disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

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.

Transcranial magnetic stimulation: physics, electrophysiology, and applications.

PubMed

Fatemi-Ardekani, Ali

2008-01-01

Transcranial magnetic stimulation (TMS) is a noninvasive technique used to stimulate the brain. This review will examine the fundamental principles of physics upon which magnetic stimulation is based, the design considerations of the TMS device, and hypotheses about its electrophysiological effects resulting in neuromodulation. TMS is valuable in neurophysiology research and has significant therapeutic potential in clinical neurology and psychiatry. While TMS can modify neuronal currents in the brain, its underlying mechanism remains unknown. Salient applications are included and some suggestions are outlined for future development of magnetic stimulators that could lead to more effective neuronal stimulation and therefore better therapeutic and diagnostic applications.

The MDS-UPDRS tracks motor and non-motor improvement due to subthalamic nucleus deep brain stimulation in Parkinson disease.

PubMed

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.

The H2O2 scavenger ebselen decreases ethanol-induced locomotor stimulation in mice.

PubMed

Ledesma, Juan Carlos; Font, Laura; Aragon, Carlos M G

2012-07-01

In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H(2)O(2) in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H(2)O(2) scavenger, on ethanol-induced locomotion. Swiss RjOrl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; IP) before caffeine (15mg/kg; IP), amphetamine (2mg/kg; IP) or cocaine (10mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H(2)O(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT). Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity. Taken together, these data suggest that a decline in H(2)O(2) levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for H(2)O(2) in some of the psychopharmacological effects produced by ethanol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Interactive Learning to Stimulate the Brain's Visual Center and to Enhance Memory Retention

ERIC Educational Resources Information Center

Yun, Yang H.; Allen, Philip A.; Chaumpanich, Kritsakorn; Xiao, Yingcai

2014-01-01

This short paper describes an ongoing NSF-funded project on enhancing science and engineering education using the latest technology. More specifically, the project aims at developing an interactive learning system with Microsoft Kinect™ and Unity3D game engine. This system promotes active, rather than passive, learning by employing embodied…

Helping Children with Sensory Processing Disorders: The Role of Occupational Therapy

ERIC Educational Resources Information Center

Sweet, Margarita

2010-01-01

Normally functioning sensory systems develop through sensory experiences. Children are stimulated through their senses in many different ways. Even though a person's sensory system is intact, he or she may have a sensory processing disorder (SPD), also known as sensory integration dysfunction. This means the person's brain does not correctly…

A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing.

PubMed

Murakami, Tatsuya C; Mano, Tomoyuki; Saikawa, Shu; Horiguchi, Shuhei A; Shigeta, Daichi; Baba, Kousuke; Sekiya, Hiroshi; Shimizu, Yoshihiro; Tanaka, Kenji F; Kiyonari, Hiroshi; Iino, Masamitsu; Mochizuki, Hideki; Tainaka, Kazuki; Ueda, Hiroki R

2018-04-01

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

A fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge.

PubMed

Piangerelli, Marco; Ciavarro, Marco; Paris, Antonino; Marchetti, Stefano; Cristiani, Paolo; Puttilli, Cosimo; Torres, Napoleon; Benabid, Alim Louis; Romanelli, Pantaleo

2014-01-01

Wireless transmission of cortical signals is an essential step to improve the safety of epilepsy procedures requiring seizure focus localization and to provide chronic recording of brain activity for Brain Computer Interface (BCI) applications. Our group developed a fully implantable and externally rechargeable device, able to provide wireless electrocorticographic (ECoG) recording and cortical stimulation (CS). The first prototype of a wireless multi-channel very low power ECoG system was custom-designed to be implanted on non-human primates. The device, named ECOGIW-16E, is housed in a compact hermetically sealed Polyether ether ketone (PEEK) enclosure, allowing seamless battery recharge. ECOGIW-16E is recharged in a wireless fashion using a special cage designed to facilitate the recharge process in monkeys and developed in accordance with guidelines for accommodation of animals by Council of Europe (ETS123). The inductively recharging cage is made up of nylon and provides a thoroughly novel experimental setting on freely moving animals. The combination of wireless cable-free ECoG and external seamless battery recharge solves the problems and shortcomings caused by the presence of cables leaving the skull, providing a safer and easier way to monitor patients and to perform ECoG recording on primates. Data transmission exploits the newly available Medical Implant Communication Service band (MICS): 402-405 MHz. ECOGIW-16E was implanted over the left sensorimotor cortex of a macaca fascicularis to assess the feasibility of wireless ECoG monitoring and brain mapping through CS. With this device, we were able to record the everyday life ECoG signal from a monkey and to deliver focal brain stimulation with movement elicitation.

High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

PubMed

Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

2016-01-01

Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

Apparent isotropic electrical property for electrical brain stimulation (EBS) using magnetic resonance diffusion weighted imaging (MR-DWI)

NASA Astrophysics Data System (ADS)

Lee, Mun Bae; Kwon, Oh-In

2018-04-01

Electrical brain stimulation (EBS) is an invasive electrotherapy and technique used in brain neurological disorders through direct or indirect stimulation using a small electric current. EBS has relied on computational modeling to achieve optimal stimulation effects and investigate the internal activations. Magnetic resonance diffusion weighted imaging (DWI) is commonly useful for diagnosis and investigation of tissue functions in various organs. The apparent diffusion coefficient (ADC) measures the intensity of water diffusion within biological tissues using DWI. By measuring trace ADC and magnetic flux density induced by the EBS, we propose a method to extract electrical properties including the effective extracellular ion-concentration (EEIC) and the apparent isotropic conductivity without any auxiliary additional current injection. First, the internal current density due to EBS is recovered using the measured one component of magnetic flux density. We update the EEIC by introducing a repetitive scheme called the diffusion weighting J-substitution algorithm using the recovered current density and the trace ADC. To verify the proposed method, we study an anesthetized canine brain to visualize electrical properties including electrical current density, effective extracellular ion-concentration, and effective isotropic conductivity by applying electrical stimulation of the brain.

Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.

PubMed

Swann, Nicole C; de Hemptinne, Coralie; Miocinovic, Svjetlana; Qasim, Salman; Ostrem, Jill L; Galifianakis, Nicholas B; Luciano, Marta San; Wang, Sarah S; Ziman, Nathan; Taylor, Robin; Starr, Philip A

2018-02-01

OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation paradigms. Clinical trial registration no.: NCT01934296 (clinicaltrials.gov).

Psychological Effects of Stimulant Drugs in Children with Minimal Brain Dysfunction

ERIC Educational Resources Information Center

Conners, C. Keith

1972-01-01

Two technical studies involving the drugs dextroamphetamine, methylphenidate, and magnesium pemoline were reported in regard to the psychological characteristics and effects of stimulant drugs in children with minimal brain injuries. (CB)

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

21 CFR 882.5840 - Implanted intracerebral/subcortical stimulator for pain relief.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to subsurface areas of a patient's brain to treat severe intractable pain. The stimulator consists of an implanted receiver with electrodes that are placed within a patient's brain and an external...

Calculating the electric field in real human head by transcranial magnetic stimulation with shield plate

NASA Astrophysics Data System (ADS)

Lu, Mai; Ueno, Shoogo

2009-04-01

In this paper, we present a transcranial magnetic stimulation (TMS) system by incorporating a conductive shield plate. The magnetic field, induced current density, and electric field in a real human head were calculated by impedance method and the results were compared with TMS without shielding. Our results show that the field localization can be improved by introducing a conductive shield plate; the stimulation magnitude (depth) in the brain is reduced comparing with the TMS without shielding. The strong magnetic field near the TMS coil is difficult to be efficiently shielded by a thinner conductive shield plate.

Same-session functional assessment of rat retina and brain with manganese-enhanced MRI

PubMed Central

Bissig, David; Berkowitz, Bruce A.

2013-01-01

Manganese-enhanced MRI (MEMRI) is a powerful non-invasive approach for objectively measuring either retina or binocular visual brain activity in vivo. In this study, we investigated the sensitivity of MEMRI to monocular stimulation using a new protocol for providing within-subject functional comparisons in the retina and brain in the same scanning session. Adult Sprague Dawley or Long–Evans rats had one eye covered with an opaque patch. After intraperitoneal Mn2+ administration on the following day, rats underwent visual stimulation for 8 h. Animals were then anesthetized, and the brain and each eye examined by MEMRI. Function was assessed through pairwise comparisons of the patched (dark-adapted) versus unpatched (light-exposed) eyes, and of differentially-stimulated brain structures – the dorsal lateral geniculate nucleus, superior colliculus, and visual cortical regions – contralateral to the patched versus unpatched eye. As expected, Mn2+ uptake was greater in the outer retina of dark-adapted, relative to light-exposed, eyes (P<0.05). Contralateral to the unpatched eye, significantly more Mn2+ uptake was found throughout the visual brain regions than in the corresponding structures contralateral to the patched eye (P<0.05). Notably, this regional pattern of activity corresponded well to previous work with monocular stimulation. No stimulation-dependent differences in Mn2+ uptake were observed in negative control brain regions (P>0.05). Post-hoc assessment of functional data by animal age and strain revealed no significant effects. These results demonstrate, for the first time, the acquisition of functional MRI data from the eye and visual brain regions in a single scanning session. PMID:21749922

Impact of Behavioral Control on the Processing of Nociceptive Stimulation

PubMed Central

Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

2012-01-01

How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

[Changes of brain pain center and default mode network an electro acupuncture in Weizhong and Dachangshu acupoints: a task-fMRI study].

PubMed

Zhou, S; Cao, H X; Yu, L C; Jin, Y J; Jia, R H; Wen, Y R; Chen, X F

2016-02-23

To investigate the functional brain pain center and default mode network response to electro acupuncture stimulate in weizhong acupoints(BL40) and dachangshu acupoints(BL25). During January to February 2015, volunteers were enrolled in this study from the staff and student interns of Gansu Province Traditional Chinese Medicine Hospital. A total of 20 healthy, right-handed subjects, male 9, female 11, age (23±3) years, participated in this study. Block design task functional magnetic resonance imaging(fMRI) 3.0 T was performed in all subjects by electro acupuncture stimulating at BL40 and BL25 from the same experienced acupuncturist.The needle connected electric acupuncture apparatus through tow long coaxial-cable. A block design with five 120 s blocks of rest time (OFF block, electric acupuncture turn off ) interspersed between five 60 s blocks of stimulation (ON block, electric acupuncture turn on) fMRI scan. Magnetic resonance data of brain function was collected and FSL(fMRI Software Library) software was used to analyze the data. All subjects' data were analyzed except 2 cases whose head movement were more than 2 mm. Activated brain function regions by electro acupuncture stimulate included temporal lobe lateral sulcus, lobus insularis, thalamus, supramarginal gyrus, prefrontal medial frontal gyrus. Negative activated brain regions included middle frontal gyrus, parahippocampal gyrus, cingulate cortex abdominal segment, parietal cortex.The functional pain central and default mode network were changed when electro acupuncture stimulate in(BL40) and(BL25). There are several brain activation regions and negative activated brain regions when administering electro acupuncture stimulation at BL40 and BL25.

Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

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

Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack

During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET-¹⁸FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared tomore » placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.« less

Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

DOE PAGES

Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; ...

2015-02-18

During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET-¹⁸FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared tomore » placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.« less

Closed-loop optical neural stimulation based on a 32-channel low-noise recording system with online spike sorting

NASA Astrophysics Data System (ADS)

Nguyen, T. K. T.; Navratilova, Z.; Cabral, H.; Wang, L.; Gielen, G.; Battaglia, F. P.; Bartic, C.

2014-08-01

Objective. Closed-loop operation of neuro-electronic systems is desirable for both scientific and clinical (neuroprosthesis) applications. Integrating optical stimulation with recording capability further enhances the selectivity of neural stimulation. We have developed a system enabling the local delivery of optical stimuli and the simultaneous electrical measuring of the neural activities in a closed-loop approach. Approach. The signal analysis is performed online through the implementation of a template matching algorithm. The system performance is demonstrated with the recorded data and in awake rats. Main results. Specifically, the neural activities are simultaneously recorded, detected, classified online (through spike sorting) from 32 channels, and used to trigger a light emitting diode light source using generated TTL signals. Significance. A total processing time of 8 ms is achieved, suitable for optogenetic studies of brain mechanisms online.

Structural, Metabolic, and Functional Brain Abnormalities as a Result of Prenatal Exposure to Drugs of Abuse: Evidence from Neuroimaging

PubMed Central

Roussotte, Florence; Soderberg, Lindsay

2010-01-01

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse. PMID:20978945

Thoracic surgery in patients with an implanted neurostimulator device.

PubMed

Meyring, Kristina; Zehnder, Adrian; Schmid, Ralph A; Kocher, Gregor J

2017-10-01

Movement disorders such as Parkinson's disease are increasingly treated with deep brain stimulators. Being implanted in a subcutaneous pocket in the chest region, thoracic surgical procedures can interfere with such devices, as they are sensible to external electromagnetic forces. Monopolar electrocautery can lead to dysfunction of the device or damage of the brain tissue caused by heat. We report a series of 3 patients with deep brain stimulators who underwent thoracic surgery. By turning off the deep brain stimulators before surgery and avoiding the use of monopolar cautery, electromagnetic interactions were avoided in all patients. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation.

PubMed

Hsueh, P-T; Lin, H-H; Wang, H-H; Liu, C-L; Ni, W-F; Liu, J-K; Chang, H-H; Sun, D-S; Chen, Y-S; Chen, Y-L

2018-04-15

The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that upregulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring. In this study, a C57BL/6j MIA female offspring model exhibiting social deficits was established. The expression of fetal interferon (IFN)-stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic upregulation of endogenous IL-10 occurred at the adult stage, while both IL-1β and IL-6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL-6 levels were endogenously upregulated, but both MCP-1 (macrophage inflammatory protein-1) and L-selectin levels were downregulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting the MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines, chemokines and CAMs were increased. Particularly, both MCP-1 and L-selectin showed relatively high expression in the brain compared with the expression levels in phosphate-buffered saline (PBS)-treated offspring injected with LPS. Potentially, MCP-1 was attracted to the L-selectin-mediated immune cells due to augmentation of the immune response following stimulation in MIA female offspring. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Neurostimulation to improve level of consciousness in patients with epilepsy.

PubMed

Gummadavelli, Abhijeet; Kundishora, Adam J; Willie, Jon T; Andrews, John P; Gerrard, Jason L; Spencer, Dennis D; Blumenfeld, Hal

2015-06-01

When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain.

Equivalent brain SPECT perfusion changes underlying therapeutic efficiency in pharmacoresistant depression using either high-frequency left or low-frequency right prefrontal rTMS.

PubMed

Richieri, Raphaëlle; Boyer, Laurent; Padovani, Romain; Adida, Marc; Colavolpe, Cécile; Mundler, Olivier; Lançon, Christophe; Guedj, Eric

2012-12-03

Functional neuroimaging studies have suggested similar mechanisms underlying antidepressant effects of distinct therapeutics. This study aimed to determine and compare functional brain patterns underlying the antidepressant response of 2 distinct protocols of repetitive transcranial magnetic stimulation (rTMS). 99mTc-ECD SPECT was performed before and after rTMS of dorsolateral prefrontal cortex in 61 drug-resistant right-handed patients with major depression, using high frequency (10Hz) left-side stimulation in 33 patients, and low frequency (1Hz) right-side stimulation in 28 patients. Efficiency of rTMS response was defined as at least 50% reduction of the baseline Beck Depression Inventory score. We compared the whole-brain voxel-based brain SPECT changes in perfusion after rTMS, between responders and non-responders in the whole sample (p<0.005, uncorrected), and separately in the subgroup of patients with left- and right-stimulation. Before rTMS, the left- and right-prefrontal stimulation groups did not differ from clinical data and brain SPECT perfusion. rTMS efficiency (evaluated on % of responders) was statistically equivalent in the two groups of patients. In the whole-group of responder patients, a perfusion decrease was found after rTMS, in comparison to non-responders, within the left perirhinal cortex (BA35, BA36). This result was secondarily confirmed separately in the two subgroups, i.e. after either left stimulation (p=0.017) or right stimulation (p<0.001), without significant perfusion differences between these two subgroups. These data show that distinct successful rTMS protocols induce equivalent brain functional changes associated to antidepressive efficiency, consisting to a remote brain limbic activity decrease within the left perirhinal cortex. However, these results will have to be confirmed in a double-blind randomized trial using a sham control group. Copyright © 2012 Elsevier Inc. All rights reserved.

Linking neuronal brain activity to the glucose metabolism.

PubMed

Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

2013-08-29

Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

Linking neuronal brain activity to the glucose metabolism

PubMed Central

2013-01-01

Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

Neurostimulation for Drug-Resistant Epilepsy

PubMed Central

DeGiorgio, Christopher M.; Krahl, Scott E.

2013-01-01

Purpose of Review: The purpose of this review is to provide an evidence-based update on the neurostimulation options available for patients with drug-resistant epilepsy in the United States and in European countries. Recent Findings: The field of neurostimulation for epilepsy has grown dramatically since 1997, when vagus nerve stimulation became the first device to be approved for epilepsy by the US Food and Drug Administration (FDA). New data from recently completed randomized controlled trials are available for deep brain stimulation of the anterior thalamus, responsive neurostimulation, and trigeminal nerve stimulation. Although vagus nerve stimulation is the only device currently approved in the United States, deep brain stimulation and responsive neurostimulation devices are awaiting FDA approval. Deep brain stimulation, trigeminal nerve stimulation, and transcutaneous vagus nerve stimulation are now approved for epilepsy in the European Union. In this article, the mechanisms of action, safety, and efficacy of new neurostimulation devices are reviewed, and the key advantages and disadvantages of each are discussed. Summary: The exponential growth of the field of neuromodulation for epilepsy is an exciting development; these new devices provide physicians with new options for patients with drug-resistant epilepsy. PMID:23739108

Mirth and laughter elicited during brain stimulation.

PubMed

Fernández-Baca Vaca, Guadalupe; Lüders, Hans O; Basha, Maysaa Merhi; Miller, Jonathan P

2011-12-01

There are few reports of laughter and/or mirth evoked by electrical stimulation of the brain. In this study, we present a patient with intractable epilepsy in whom mirth and laughter was consistently produced during stimulation of the left inferior frontal gyrus (opercular part) using stereotactically placed depth electrodes. A review of the literature shows that cortical sites that produce mirth when stimulated are located in the dominant hemisphere close to language areas or cortical negative motor areas.

Cognitive Enhancement or Cognitive Cost: Trait-Specific Outcomes of Brain Stimulation in the Case of Mathematics Anxiety

PubMed Central

Sarkar, Amar; Dowker, Ann

2014-01-01

The surge in noninvasive brain stimulation studies investigating cognitive enhancement has neglected the effect of interindividual differences, such as traits, on stimulation outcomes. Using the case of mathematics anxiety in a sample of healthy human participants in a placebo-controlled, double-blind, crossover experiment, we show that identical transcranial direct current stimulation (tDCS) exerts opposite behavioral and physiological effects depending on individual trait levels. Mathematics anxiety is the negative emotional response elicited by numerical tasks, impairing mathematical achievement. tDCS was applied to the dorsolateral prefrontal cortex, a frequent target for modulating emotional regulation. It improved reaction times on simple arithmetic decisions and decreased cortisol concentrations (a biomarker of stress) in high mathematics anxiety individuals. In contrast, tDCS impaired reaction times for low mathematics anxiety individuals and prevented a decrease in cortisol concentration compared with sham stimulation. Both groups showed a tDCS-induced side effect—impaired executive control in a flanker task—a cognitive function subserved by the stimulated region. These behavioral and physiological double dissociations have implications for brain stimulation research by highlighting the role of individual traits in experimental findings. Brain stimulation clearly does not produce uniform benefits, even applied in the same configuration during the same tasks, but may interact with traits to produce markedly opposed outcomes. PMID:25505313

Cognitive enhancement or cognitive cost: trait-specific outcomes of brain stimulation in the case of mathematics anxiety.

PubMed

Sarkar, Amar; Dowker, Ann; Cohen Kadosh, Roi

2014-12-10

The surge in noninvasive brain stimulation studies investigating cognitive enhancement has neglected the effect of interindividual differences, such as traits, on stimulation outcomes. Using the case of mathematics anxiety in a sample of healthy human participants in a placebo-controlled, double-blind, crossover experiment, we show that identical transcranial direct current stimulation (tDCS) exerts opposite behavioral and physiological effects depending on individual trait levels. Mathematics anxiety is the negative emotional response elicited by numerical tasks, impairing mathematical achievement. tDCS was applied to the dorsolateral prefrontal cortex, a frequent target for modulating emotional regulation. It improved reaction times on simple arithmetic decisions and decreased cortisol concentrations (a biomarker of stress) in high mathematics anxiety individuals. In contrast, tDCS impaired reaction times for low mathematics anxiety individuals and prevented a decrease in cortisol concentration compared with sham stimulation. Both groups showed a tDCS-induced side effect-impaired executive control in a flanker task-a cognitive function subserved by the stimulated region. These behavioral and physiological double dissociations have implications for brain stimulation research by highlighting the role of individual traits in experimental findings. Brain stimulation clearly does not produce uniform benefits, even applied in the same configuration during the same tasks, but may interact with traits to produce markedly opposed outcomes. Copyright © 2014 Sarkar et al.

Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning

PubMed Central

Wise, Richard J.S.; Geranmayeh, Fatemeh; Hampshire, Adam

2017-01-01

It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword–object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary. SIGNIFICANCE STATEMENT Learning a task involves the brain system within which that specific task becomes established. Therefore, successfully learning a new vocabulary establishes the novel words in the language system. However, there is evidence that in the early stages of learning, networks within multiple-demand cortex (MDC), which control higher cognitive functions, such as working memory, attention, and monitoring of performance, become active. This activity declines once the task is learnt. The present study demonstrated that a node within MDC, located in midline frontal cortex, becomes active during the early stage of learning a novel vocabulary. Importantly, noninvasive brain stimulation of this node improved performance during this stage of learning. This observation demonstrated that MDC activity is important for learning. PMID:28676576

CranialVault and its CRAVE tools: a clinical computer assistance system for Deep Brain Stimulation (DBS) therapy

PubMed Central

D’Haese, Pierre-François; Pallavaram, Srivatsan; Li, Rui; Remple, Michael S.; Kao, Chris; Neimat, Joseph S.; Konrad, Peter E.; Dawant, Benoit M.

2010-01-01

A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAVE (CRAnialVault Explorer) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information. PMID:20732828

[Fundamentals and Clinical Applications of Transcranial Magnetic Stimulation in Neuropsychiatry].

PubMed

Malavera, Mayra; Silva, Federico; García, Ronald; Rueda, Ligia; Carrillo, Sandra

2014-03-01

Transcranial Magnetic Stimulation (TMS) is a non-invasive method for stimulation of brain that is based on the ability of a generated magnetic field to penetrate skull and brain meninges, inducing an electric current in the brain tissues that produces neuronal depolarization. TMS can be applied as single pulse of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. Its mechanism of action is currently unknown. Repetitive TMS can modify the excitability of the cerebral cortex, and has been postulated as a diagnostic and therapeutic tool in the area of neuropsychiatry. The aim of this article is to review the knowledge of the TMS as regards its basic principles, pathophysiological mechanism, and its usefulness in clinical practice. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning.

PubMed

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.

Neuroelectronics and modeling of electrical signals for monitoring and control of Parkinson's disease

NASA Astrophysics Data System (ADS)

Chintakuntla, Ritesh R.; Abraham, Jose K.; Varadan, Vijay K.

2009-03-01

The brain and the human nervous system are perhaps the most researched but least understood components of the human body. This is so because of the complex nature of its working and the high density of functions. The monitoring of neural signals could help one better understand the working of the brain and newer recording and monitoring methods have been developed ever since it was discovered that the brain communicates internally by means of electrical pulses. Neuroelectronics is the field which deals with the interface between electronics or semiconductors to living neurons. This includes monitoring of electrical activity from the brain as well as the development of feedback devices for stimulation of parts of the brain for treatment of disorders. In this paper these electrical signals are modeled through a nano/microelectrode arrays based on the electronic equivalent model using Cadence PSD 15.0. The results were compared with those previously published models such as Kupfmuller and Jenik's model, McGrogan's Neuron Model which are based on the Hodgkin and Huxley model. We have developed and equivalent circuit model using discrete passive components to simulate the electrical activity of the neurons. The simulated circuit can be easily be modified by adding some more ionic channels and the results can be used to predict necessary external stimulus needed for stimulation of neurons affected by the Parkinson's disease (PD). Implementing such a model in PD patients could predict the necessary voltages required for the electrical stimulation of the sub-thalamus region for the control tremor motion.

The Use of Brain Stimulation in Dysphagia Management.

PubMed

Simons, Andre; Hamdy, Shaheen

2017-04-01

Dysphagia is common sequela of brain injury with as many as 50% of patients suffering from dysphagia following stroke. Currently, the majority of guidelines for clinical practice in the management of dysphagia focus on the prevention of complications while any natural recovery takes place. Recently, however, non-invasive brain stimulation (NIBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have started to attract attention and are applied to investigate both the physiology of swallowing and influences on dysphagia. TMS allows for painless stimulation of the brain through an intact skull-an effect which would normally be impossible with electrical currents due to the high resistance of the skull. By comparison, tDCS involves passing a small electric current (usually under 2 mA) produced by a current generator over the scalp and cranium external to the brain. Initial studies used these techniques to better understand the physiological mechanisms of swallowing in healthy subjects. More recently, a number of studies have investigated the efficacy of these techniques in the management of neurogenic dysphagia with mixed results. Controversy still exists as to which site, strength and duration of stimulation yields the greatest improvement in dysphagia. And while multiple studies have suggested promising effects of NIBS, more randomised control trials with larger sample sizes are needed to investigate the short- and long-term effects of NIBS in neurogenic dysphagia.

Task-dependent activity and connectivity predict episodic memory network-based responses to brain stimulation in healthy aging

PubMed Central

Vidal-Piñeiro, Dídac; Martin-Trias, Pablo; Arenaza-Urquijo, Eider M.; Sala-Llonch, Roser; Mena-Sánchez, Isaias; Bargalló, Núria; Falcón, Carles; Pascual-Leone, Álvaro; Bartrés-Faz, David

2015-01-01

Background Transcranial Magnetic Stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. Objectives To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. Methods We applied a paradigm of repetitive TMS -intermittent theta-burst stimulation- over left inferior frontal gyrus in healthy elders (n=24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. Results In the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. Conclusions The results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches. PMID:24485466

Task-dependent activity and connectivity predict episodic memory network-based responses to brain stimulation in healthy aging.

PubMed

Vidal-Piñeiro, Dídac; Martin-Trias, Pablo; Arenaza-Urquijo, Eider M; Sala-Llonch, Roser; Clemente, Imma C; Mena-Sánchez, Isaias; Bargalló, Núria; Falcón, Carles; Pascual-Leone, Álvaro; Bartrés-Faz, David

2014-01-01

Transcranial magnetic stimulation (TMS) can affect episodic memory, one of the main cognitive hallmarks of aging, but the mechanisms of action remain unclear. To evaluate the behavioral and functional impact of excitatory TMS in a group of healthy elders. We applied a paradigm of repetitive TMS - intermittent theta-burst stimulation - over left inferior frontal gyrus in healthy elders (n = 24) and evaluated its impact on the performance of an episodic memory task with two levels of processing and the associated brain activity as captured by a pre and post fMRI scans. In the post-TMS fMRI we found TMS-related activity increases in left prefrontal and cerebellum-occipital areas specifically during deep encoding but not during shallow encoding or at rest. Furthermore, we found a task-dependent change in connectivity during the encoding task between cerebellum-occipital areas and the TMS-targeted left inferior frontal region. This connectivity change correlated with the TMS effects over brain networks. The results suggest that the aged brain responds to brain stimulation in a state-dependent manner as engaged by different tasks components and that TMS effect is related to inter-individual connectivity changes measures. These findings reveal fundamental insights into brain network dynamics in aging and the capacity to probe them with combined behavioral and stimulation approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

Tourette syndrome and other chronic tic disorders: an update on clinical management.

PubMed

Martino, Davide; Pringsheim, Tamara M

2018-02-01

The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage. Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment', 'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial current stimulation'. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of novelty and impact. Expert commentary: Comprehensive assessment of tic disorders and psychoeducation are crucial to a correct active management approach. Behavioral treatments represent first line of active interventions, with increasing potential offered by telehealth. Antipsychotics and alpha agonists remain first line pharmacological interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain stimulation is a potential option for medically refractory, severely disabled patients with tics, but age and target selection require further investigation.

Electromagnetic characteristics of eccentric figure-eight coils for transcranial magnetic stimulation: A numerical study

NASA Astrophysics Data System (ADS)

Kato, Takuya; Sekino, Masaki; Matsuzaki, Taiga; Nishikawa, Atsushi; Saitoh, Youichi; Ohsaki, Hiroyuki

2012-04-01

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment of several neurological and psychiatric diseases. We proposed an eccentric figure-eight coil, which induces strong eddy currents in the target brain tissue. In this study, numerical analyses were carried out to obtain magnetic field distribution of the eccentric figure-eight coil and eddy current in the brain. The analyses were performed with various coil design parameters, such as the outer and inner diameters and number of turns, to investigate the influence of these parameters on the coil characteristics. Increases in the inner diameter, outer diameter, and number of turns caused increases in the maximum eddy current densities. Coil inductance, working voltage, and heat generation also became higher with the increases in these design parameters. In order to develop a compact stimulator system for use at home, we need to obtain strong eddy current density, keeping the working voltage as low as possible. Our results show that it is effective to enlarge the outer diameter.

Sex, Drugs and Gluttony: How the Brain Controls Motivated Behaviors

PubMed Central

Hull, Elaine M.

2011-01-01

Bart Hoebel has forged a view of an integrated neural network that mediates both natural rewards and drug use. He pioneered the use of microdialysis, and also effectively used electrical stimulation, lesions, microinjections, and immunohistochemistry. He found that feeding, stimulant drug administration, and electrical stimulation of the lateral hypothalamus (LH) all increased dopamine (DA) release in the nucleus accumbens (NAc). However, whereas DA in the NAc enhanced motivation, DA in the LH inhibited motivated behaviors. The Hull lab has pursued some of those ideas. We have suggested that serotonin (5-HT) in the perifornicalLH inhibits sexual behavior by inhibiting orexin/hypocretin neurons (OX/HCRT), which would otherwise excite neurons in the mesocorticolimbic DA tract. We have shown that DA release in the medial preoptic area (MPOA) is very important for male sexual behavior, and that testosterone, glutamate, nitric oxide (NO) and previous sexual experience promote MPOA DA release and mating. Future research should follow Bart Hoebel’s emphasis on neural systems and interactions among brain areas and neurotransmitters. PMID:21554895

A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback.

PubMed

Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A

2014-10-01

Present day cortical brain-machine interfaces (BMIs) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available. To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation to provide 'tactile' sensation to a non-human primate. Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area, the parietal reach region and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. Providing somatosensory feedback has the poyential to greatly improve the performance of cognitive neuroprostheses especially for fine control and object manipulation. Adding stimulation to a BMI system could therefore improve the quality of life for severely paralyzed patients.

Action of AF64A on rat brain muscarinic receptors

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

Eva, C.; Costa, E.

ICV administration of compound AF64A (ethylcholine mustard aziridium ion) induces a long-term selective cholinergic hypofunction; however, it does not modify the characteristics of muscarinic receptors. In brain muscarinic receptor activation can either stimulate phosphoinositide turnover or inhibit adenylate cyclase. ICV infusion of AF64A (5 nmol/side/2.5 ..mu..l) reduced the hippocampal ACh content 10 or 30 days after the treatment to 75% of the control values. Under these conditions neither in the striatum nor in the frontal cortex ACh levels were decreased. The carbachol dose-dependent stimulation in hippocampal slices differed from that observed in control rats. The carbachol efficacy was increased butmore » its potency was unchanged by AF64A. In contrast, ICV administration of AF64A failed to alter the oxotremorine efficacy or potency in inhibiting the forskolin stimulated adenylate cyclase in rat hippocampal membranes. These results suggest the two transducer systems coupled to muscarinic receptors may be differentially regulatable by cholinergic input.« less

The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices

PubMed Central

2012-01-01

Background A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Methods Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10–20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Results Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Conclusions Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections. PMID:23199306

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia

PubMed Central

Lei, Beilei; Mace, Brian; Dawson, Hana N.; Warner, David S.; Laskowitz, Daniel T.; James, Michael L.

2014-01-01

Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone’s effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury. PMID:25080336

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

PubMed

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.

Computational modeling of neurostimulation in brain diseases.

PubMed

Wang, Yujiang; Hutchings, Frances; Kaiser, Marcus

2015-01-01

Neurostimulation as a therapeutic tool has been developed and used for a range of different diseases such as Parkinson's disease, epilepsy, and migraine. However, it is not known why the efficacy of the stimulation varies dramatically across patients or why some patients suffer from severe side effects. This is largely due to the lack of mechanistic understanding of neurostimulation. Hence, theoretical computational approaches to address this issue are in demand. This chapter provides a review of mechanistic computational modeling of brain stimulation. In particular, we will focus on brain diseases, where mechanistic models (e.g., neural population models or detailed neuronal models) have been used to bridge the gap between cellular-level processes of affected neural circuits and the symptomatic expression of disease dynamics. We show how such models have been, and can be, used to investigate the effects of neurostimulation in the diseased brain. We argue that these models are crucial for the mechanistic understanding of the effect of stimulation, allowing for a rational design of stimulation protocols. Based on mechanistic models, we argue that the development of closed-loop stimulation is essential in order to avoid inference with healthy ongoing brain activity. Furthermore, patient-specific data, such as neuroanatomic information and connectivity profiles obtainable from neuroimaging, can be readily incorporated to address the clinical issue of variability in efficacy between subjects. We conclude that mechanistic computational models can and should play a key role in the rational design of effective, fully integrated, patient-specific therapeutic brain stimulation. © 2015 Elsevier B.V. All rights reserved.

Brain Stimulation Studies of Social Norm Compliance: Implications for Personality Disorders?

PubMed

Ruff, Christian C

2018-01-01

Several personality disorders involve pathological behaviors that violate social norms, commonly held expectations about what ought to be done in specific situations. These symptoms usually emerge early in development, are persistent and hard to treat, and are often ego-syntonic. Here I present some recent brain stimulation studies suggesting that pathological changes in different aspects of norm-compliant behavior reflect dysfunctions of brain circuits involving distinct prefrontal brain areas. One set of studies shows that transcranial direct current stimulation of the right lateral prefrontal cortex changes the behavioral sensitivity to social incentives for norm-compliant behavior. Crucially, social norm compliance in response to such incentives could even be increased during excitatory stimulation, demonstrating that the affected neural process is a biological prerequisite for appropriate reaction to social signals that trigger norm compliance. In another set of studies, we show that stimulation of a different (more dorsal) part of the right prefrontal cortex enhances honesty in a realistic setting where participants had the opportunity to cheat for real monetary gains. Interestingly, these stimulation-induced increases in both socially cued or purely voluntary norm compliance were not linked to changes in other aspects of decision- making (such as risk or impatience), and they did not reflect changes in beliefs about what is appropriate behavior. These results suggest that disorders of distinct brain circuits may causally underlie egosyntotic changes in norm-compliant behavior. This raises the tantalizing possibility that pathologies of norm-compliant behavior may be ameliorated by interventions targeting the function of these brain circuits. © 2018 S. Karger AG, Basel.

Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

PubMed

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.

Music in Research and Rehabilitation of Disorders of Consciousness: Psychological and Neurophysiological Foundations.

PubMed

Kotchoubey, Boris; Pavlov, Yuri G; Kleber, Boris

2015-01-01

According to a prevailing view, the visual system works by dissecting stimuli into primitives, whereas the auditory system processes simple and complex stimuli with their corresponding features in parallel. This makes musical stimulation particularly suitable for patients with disorders of consciousness (DoC), because the processing pathways related to complex stimulus features can be preserved even when those related to simple features are no longer available. An additional factor speaking in favor of musical stimulation in DoC is the low efficiency of visual stimulation due to prevalent maladies of vision or gaze fixation in DoC patients. Hearing disorders, in contrast, are much less frequent in DoC, which allows us to use auditory stimulation at various levels of complexity. The current paper overviews empirical data concerning the four main domains of brain functioning in DoC patients that musical stimulation can address: perception (e.g., pitch, timbre, and harmony), cognition (e.g., musical syntax and meaning), emotions, and motor functions. Music can approach basic levels of patients' self-consciousness, which may even exist when all higher-level cognitions are lost, whereas music induced emotions and rhythmic stimulation can affect the dopaminergic reward-system and activity in the motor system respectively, thus serving as a starting point for rehabilitation.

Music in Research and Rehabilitation of Disorders of Consciousness: Psychological and Neurophysiological Foundations

PubMed Central

Kotchoubey, Boris; Pavlov, Yuri G.; Kleber, Boris

2015-01-01

According to a prevailing view, the visual system works by dissecting stimuli into primitives, whereas the auditory system processes simple and complex stimuli with their corresponding features in parallel. This makes musical stimulation particularly suitable for patients with disorders of consciousness (DoC), because the processing pathways related to complex stimulus features can be preserved even when those related to simple features are no longer available. An additional factor speaking in favor of musical stimulation in DoC is the low efficiency of visual stimulation due to prevalent maladies of vision or gaze fixation in DoC patients. Hearing disorders, in contrast, are much less frequent in DoC, which allows us to use auditory stimulation at various levels of complexity. The current paper overviews empirical data concerning the four main domains of brain functioning in DoC patients that musical stimulation can address: perception (e.g., pitch, timbre, and harmony), cognition (e.g., musical syntax and meaning), emotions, and motor functions. Music can approach basic levels of patients’ self-consciousness, which may even exist when all higher-level cognitions are lost, whereas music induced emotions and rhythmic stimulation can affect the dopaminergic reward-system and activity in the motor system respectively, thus serving as a starting point for rehabilitation. PMID:26640445

Functional vision in children with perinatal brain damage.

PubMed

Alimović, Sonja; Jurić, Nikolina; Bošnjak, Vlatka Mejaški

2014-09-01

Many authors have discussed the effects of visual stimulations on visual functions, but there is no research about the effects on using vision in everyday activities (i.e. functional vision). Children with perinatal brain damage can develop cerebral visual impairment with preserved visual functions (e.g. visual acuity, contrast sensitivity) but poor functional vision. Our aim was to discuss the importance of assessing and stimulating functional vision in children with perinatal brain damage. We assessed visual functions (grating visual acuity, contrast sensitivity) and functional vision (the ability of maintaining visual attention and using vision in communication) in 99 children with perinatal brain damage and visual impairment. All children were assessed before and after the visual stimulation program. Our first assessment results showed that children with perinatal brain damage had significantly more problems in functional vision than in basic visual functions. During the visual stimulation program both variables of functional vision and contrast sensitivity improved significantly, while grating acuity improved only in 2.7% of children. We also found that improvement of visual attention significantly correlated to improvement on all other functions describing vision. Therefore, functional vision assessment, especially assessment of visual attention is indispensable in early monitoring of child with perinatal brain damage.

Transcranial Magnetic Stimulation-coil design with improved focality

NASA Astrophysics Data System (ADS)

Rastogi, P.; Lee, E. G.; Hadimani, R. L.; Jiles, D. C.

2017-05-01

Transcranial Magnetic Stimulation (TMS) is a technique for neuromodulation that can be used as a non-invasive therapy for various neurological disorders. In TMS, a time varying magnetic field generated from an electromagnetic coil placed on the scalp is used to induce an electric field inside the brain. TMS coil geometry plays an important role in determining the focality and depth of penetration of the induced electric field responsible for stimulation. Clinicians and basic scientists are interested in stimulating a localized area of the brain, while minimizing the stimulation of surrounding neural networks. In this paper, a novel coil has been proposed, namely Quadruple Butterfly Coil (QBC) with an improved focality over the commercial Figure-8 coil. Finite element simulations were conducted with both the QBC and the conventional Figure-8 coil. The two coil's stimulation profiles were assessed with 50 anatomically realistic MRI derived head models. The coils were positioned on the vertex and the scalp over the dorsolateral prefrontal cortex to stimulate the brain. Computer modeling of the coils has been done to determine the parameters of interest-volume of stimulation, maximum electric field, location of maximum electric field and area of stimulation across all 50 head models for both coils.

Computer-Guided Deep Brain Stimulation Programming for Parkinson's Disease.

PubMed

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.

Brain-gut-microbiota axis in Parkinson's disease.

PubMed

Mulak, Agata; Bonaz, Bruno

2015-10-07

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

Multichannel activity propagation across an engineered axon network

NASA Astrophysics Data System (ADS)

Chen, H. Isaac; Wolf, John A.; Smith, Douglas H.

2017-04-01

Objective. Although substantial progress has been made in mapping the connections of the brain, less is known about how this organization translates into brain function. In particular, the massive interconnectivity of the brain has made it difficult to specifically examine data transmission between two nodes of the connectome, a central component of the ‘neural code.’ Here, we investigated the propagation of multiple streams of asynchronous neuronal activity across an isolated in vitro ‘connectome unit.’ Approach. We used the novel technique of axon stretch growth to create a model of a long-range cortico-cortical network, a modular system consisting of paired nodes of cortical neurons connected by axon tracts. Using optical stimulation and multi-electrode array recording techniques, we explored how input patterns are represented by cortical networks, how these representations shift as they are transmitted between cortical nodes and perturbed by external conditions, and how well the downstream node distinguishes different patterns. Main results. Stimulus representations included direct, synaptic, and multiplexed responses that grew in complexity as the distance between the stimulation source and recorded neuron increased. These representations collapsed into patterns with lower information content at higher stimulation frequencies. With internodal activity propagation, a hierarchy of network pathways, including latent circuits, was revealed using glutamatergic blockade. As stimulus channels were added, divergent, non-linear effects were observed in local versus distant network layers. Pairwise difference analysis of neuronal responses suggested that neuronal ensembles generally outperformed individual cells in discriminating input patterns. Significance. Our data illuminate the complexity of spiking activity propagation in cortical networks in vitro, which is characterized by the transformation of an input into myriad outputs over several network layers. These results provide insight into how the brain potentially processes information and generates the neural code and could guide the development of clinical therapies based on multichannel brain stimulation.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

PubMed

Ruffini, Giulio; Fox, Michael D; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-04-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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

PubMed

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

2014-01-01

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

Lightning may pose a danger to patients receiving deep brain stimulation: case report.

PubMed

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.

A PC-based system for predicting movement from deep brain signals in Parkinson's disease.

PubMed

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.

Case report of vasovagal syncope associated with single pulse transcranial magnetic stimulation in a healthy adult participant.

PubMed

Gillick, Bernadette T; Rich, Tonya; Chen, Mo; Meekins, Gregg D

2015-12-01

Non-invasive brain stimulation-related seizures or syncopal events are rare. However, we report on a syncopal event in a healthy female during a transcranial magnetic stimulation single-pulse testing session. A 47-year-old healthy female presented for a transcranial magnetic stimulation session involving single-pulse assessment of cortical excitability. During the session, the participant appeared to have a brief event involving fainting and myoclonic jerks of the upper extremities. Orthostatic assessment was performed after the event and physician evaluation determined that this was a vasovagal syncopal event. The ethical aspects of this neurophysiology testing protocol were reviewed by the University of Minnesota Institutional Review Board (IRB), and formal IRB approval was deemed unnecessary for single-pulse assessment of healthy control participants not directly involved in a research study. Informed consent was obtained by the participant, including review of potential adverse events. Although rare and rarely reported, vasovagal syncopal events surrounding non-invasive brain stimulation do occur. Thorough pre-screening should incorporate assessment of history of syncope and a plan for risk mitigation if such an event should occur. A complete assessment of the impact of stimulation on the autonomic nervous system is unknown. As such studies expand into patients with myriad neurologic diagnoses, further studies on this effect, in both healthy control and patient populations, are warranted. Such knowledge could contribute to identification of the optimal study participant, and improvements in techniques of stimulation administration.

Effect of hypergravity on expression of the immediate early gene, c-fos, in central nervous system of medaka (Oryzias latipes)

NASA Astrophysics Data System (ADS)

Sayaka, Shimomura-Umemura; Ijiri, Kenichi

2006-01-01

Immediate-early genes serve as useful neurobiological tools for mapping brain activity induced by a sensory stimulation. In this study, we have examined brain activity related to gravity perception of medaka (Oryzias latipes) by use of c-fos. The gene, which is homologous to the c-fos genes of other vertebrates, was identified in medaka. Functionally important domains are highly conserved among all the vertebrate species analyzed. Intraperitoneal administration of kainic acid transiently induced the c-fos mRNAs in medaka brains. The results indicate that the expression of c-fos can be utilized as a suitable anatomical marker for the increased neural activities in the central nervous system of medaka. Fish were continuously exposed to 3 g hypergravity by centrifugation. Investigation of c-fos mRNA expression indicated that c-fos mRNA significantly increased 30 min after a start of 3 g exposure. The distribution of its transcripts within the brains was analyzed by an in situ hybridization method. The 3-g treated medakas displayed c-fos positive cells in their brainstem regions, which are related to vestibular function, such as torus semicircularis, nucleus tangentialis, posterior octavu nucleus, and inferior olive. Our results established a method to follow the effect of gravity stimulation, which can be used to investigate gravity perception.

Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

PubMed Central

Breit, Sigrid; Kupferberg, Aleksandra; Rogler, Gerhard; Hasler, Gregor

2018-01-01

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms. PMID:29593576

Robotically-adjustable microstereotactic frames for image-guided neurosurgery

NASA Astrophysics Data System (ADS)

Kratchman, Louis B.; Fitzpatrick, J. Michael

2013-03-01

Stereotactic frames are a standard tool for neurosurgical targeting, but are uncomfortable for patients and obstruct the surgical field. Microstereotactic frames are more comfortable for patients, provide better access to the surgical site, and have grown in popularity as an alternative to traditional stereotactic devices. However, clinically available microstereotactic frames require either lengthy manufacturing delays or expensive image guidance systems. We introduce a robotically-adjusted, disposable microstereotactic frame for deep brain stimulation surgery that eliminates the drawbacks of existing microstereotactic frames. Our frame can be automatically adjusted in the operating room using a preoperative plan in less than five minutes. A validation study on phantoms shows that our approach provides a target positioning error of 0.14 mm, which exceeds the required accuracy for deep brain stimulation surgery.

Transcranial focused ultrasound stimulation of human primary visual cortex

NASA Astrophysics Data System (ADS)

Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

2016-09-01

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Deep brain stimulation mechanisms: beyond the concept of local functional inhibition.

PubMed

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.

Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation

PubMed Central

Huang, Yu; Liu, Anli A; Lafon, Belen; Friedman, Daniel; Dayan, Michael; Wang, Xiuyuan; Bikson, Marom; Doyle, Werner K; Devinsky, Orrin; Parra, Lucas C

2017-01-01

Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimated electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.8 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r = 0.86) and depth (r = 0.88) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials. DOI: http://dx.doi.org/10.7554/eLife.18834.001 PMID:28169833

Robotic Stereotaxy in Cranial Neurosurgery: A Qualitative Systematic Review.

PubMed

Fomenko, Anton; Serletis, Demitre

2017-12-14

Modern-day stereotactic techniques have evolved to tackle the neurosurgical challenge of accurately and reproducibly accessing specific brain targets. Neurosurgical advances have been made in synergy with sophisticated technological developments and engineering innovations such as automated robotic platforms. Robotic systems offer a unique combination of dexterity, durability, indefatigability, and precision. To perform a systematic review of robotic integration for cranial stereotactic guidance in neurosurgery. Specifically, we comprehensively analyze the strengths and weaknesses of a spectrum of robotic technologies, past and present, including details pertaining to each system's kinematic specifications and targeting accuracy profiles. Eligible articles on human clinical applications of cranial robotic-guided stereotactic systems between 1985 and 2017 were extracted from several electronic databases, with a focus on stereotactic biopsy procedures, stereoelectroencephalography, and deep brain stimulation electrode insertion. Cranial robotic stereotactic systems feature serial or parallel architectures with 4 to 7 degrees of freedom, and frame-based or frameless registration. Indications for robotic assistance are diversifying, and include stereotactic biopsy, deep brain stimulation and stereoelectroencephalography electrode placement, ventriculostomy, and ablation procedures. Complication rates are low, and mainly consist of hemorrhage. Newer systems benefit from increasing targeting accuracy, intraoperative imaging ability, improved safety profiles, and reduced operating times. We highlight emerging future directions pertaining to the integration of robotic technologies into future neurosurgical procedures. Notably, a trend toward miniaturization, cost-effectiveness, frameless registration, and increasing safety and accuracy characterize successful stereotactic robotic technologies. Copyright © 2017 by the Congress of Neurological Surgeons

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

PubMed

Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

2015-06-01

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

PubMed

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.

Investigation of the cortical activation by touching fabric actively using fingers.

PubMed

Wang, Q; Yu, W; He, N; Chen, K

2015-11-01

Human subjects can tactually estimate the perception of touching fabric. Although many psychophysical and neurophysiological experiments have elucidated the peripheral neural mechanisms that underlie fabric hand estimation, the associated cortical mechanisms are not well understood. To identify the brain regions responsible for the tactile stimulation of fabric against human skin, we used the technology of functional magnetic resonance imaging (fMRI), to observe brain activation when the subjects touched silk fabric actively using fingers. Consistent with previous research about brain cognition on sensory stimulation, large activation in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII) and moto cortex, and little activation in the posterior insula cortex and Broca's Area were observed when the subjects touched silk fabric. The technology of fMRI is a promising tool to observe and characterize the brain cognition on the tactile stimulation of fabric quantitatively. The intensity and extent of activation in the brain regions, especially the primary somatosensory cortex (SI) and the secondary somatosensory cortex (SII), can represent the perception of stimulation of fabric quantitatively. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.