Constant Current Stimulation Research Articles

A Neuromodulator Frontend With Reconfigurable Class-B Current and Voltage Controlled Stimulator

This letter presents a neuromodulator frontend that features a reconfigurable current and voltage mode stimulator for a bidirectional, neural interface. By implementing a capacitive high voltage (HV) to low voltage (LV) converter, a single-bit quantizer in the LV domain can be used to compare the difference between the electrode potential and the output of a 7-bit digital-to-analog converter. The digitized signal is integrated to generate a digital feedback signal, which controls a constant current stimulator in order to generate the desired output voltage by adjusting the output current. Thereby the stimulator can deliver up to ±10 mA of output current and ±6 V of stimulation voltage. The stimulation unit is connected over HV protection switches to a neural recorder that features a tunable high-pass cut-off frequency and impulse-based bioimpedance estimation, to form a bidirectional channel. The total consumed silicon area of the frontend is 0.45 mm2 for recording and stimulation. In standby mode the stimulator can be completely disconnected from its biasing, which leads to a power consumption of less than 1 ${\mu }\text{W}$ . The class-B operation during voltage stimulation yields an active power consumption, which is dominated by the stimulator output current in both voltage and current mode.

High-Throughput CMOS MEA System with Integrated Microfluidics for Cardiotoxicity Studies

High-Throughput CMOS MEA System with Integrated Microfluidics for Cardiotoxicity Studies

RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation.

Spinal cord stimulation has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after spinal cord stimulation are poorly understood. Here, we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional spinal cord stimulation treatment. Five weeks after chronic constrictive injury to the left sciatic nerve, male and female rats were randomized to receive repetitive spinal cord stimulation or no treatment. Rats receiving spinal cord stimulation underwent epidural placement of a miniature stimulating electrode and received seven sessions of spinal cord stimulation (50 Hz, 80% motor threshold, 0.2 ms, constant current bipolar stimulation, 120 min/session) over four consecutive days. Within 2 h after the last spinal cord stimulation treatment, the L4-L6 spinal segments ipsilateral to the side of nerve injury were harvested and used to generate libraries for RNA-seq. Our RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive spinal cord stimulation, including transcription of cell surface receptors and activation of non-neuronal cells. We also demonstrate that repetitive spinal cord stimulation represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density. Our transcriptional studies suggest a potential relationship between specific genes and the therapeutic effects observed in patients undergoing conventional spinal cord stimulation after nerve injury. Furthermore, our results may help identify new therapeutic targets for improving the efficacy of conventional spinal cord stimulation and other chronic pain treatments.

Effects ofdirect current on Klebsiella spp. viability and corresponding resistance gene expression in simulative bio-electrochemical reactors

The fate of antibiotic-resistant bacteria (ARB) and associated antibiotic-resistant gene (ARG) expression under electrolytic stimulation in bio-electrochemical reactors (BERs) was unknown. In this study, sulfadiazine resistant bacteria (Klebsiella spp.), which were isolated from a BER, were subjected to constant direct current (DC) stimulation in a simulated BER. With an increase of the current from 7 to 28 mA, it was found that lactic dehydrogenase (LDH) showed a 1.03-, 1.21-, 1.34-, and 1.46-fold value compared with the control at 48 h, indicating that the cell membrane permeability had increased. Since the adenosine triphosphate (ATP) concentration increased with the current, the specific growth rate of Klebsiella spp. increased (R = 0.98). The viable count of Klebsiella spp. reached a maximum at 19 mA and then decreased. The percentage of ARB lethality, which was reflected by flow cytometry analysis, increased from 18% (7 mA) to 37.8% (28 mA) at 48 h. Reactive oxygen species (ROS) produced from the electrolysis of water were greater with the increasing current (R = 0.94), which may be responsible for the high lethality rate of Klebsiella spp.. Scanning electronic microscope results showed that electrolytic stimulation changed the cell surface morphology with some cell disruption. An upregulation of sulII and int1 expression was observed. A significant correlation between int1 and the current (R = 0.97) were observed. Taken together, BERs possess potential risks in accelerating ARB multiplication and promoting ARG expression.

Feasibility of extravascular pacing with a novel substernal electrode configuration: The Substernal Pacing Acute Clinical Evaluation study

Subcutaneous implantable cardioverter-defibrillators provide an alternative to transvenous defibrillation but require higher shock outputs and offer no antitachycardia pacing. The Substernal Pacing Acute Clinical Evaluation (SPACE) study evaluated the feasibility of pacing from an extravascular substernal location. The primary purpose of the SPACE study was to characterize pacing from the substernal space. Secondary objectives included evaluating extracardiac stimulation and recording electrograms. The SPACE study prospectively evaluated the feasibility of pacing with a commercially available electrophysiology catheter acutely implanted in the substernal space via minimally invasive subxiphoid access. Pacing data were collected in ≥7 vectors using constant current stimulation up to 20 mA and pulse width up to 10 ms. Catheter placement was successful in all 26 patients whounderwent the procedure, with a mean placement time of 11.7 ± 10.1 minutes. Eighteen patients (69%) had successful ventricular capture in ≥1 tested vector. The mean pacing threshold at apulse width of 10 ms was 7.3 ± 4.2 mA across all vectors (5.8 ± 4.4 V). Failed capture was generally associated with suboptimal catheter placement or presumed air ingression. A low level of extracardiac stimulation was observed in 1 patient. The mean R-wave amplitude ranged from 2.98 to 4.11 mV in the unipolar configuration and from 0.83 to 3.95 mV in the bipolar configuration. The data from the SPACE study demonstrate that pacing is feasible from the extravascular substernal location. A substernal electrode configuration has the potential to provide pacing in a future extravascular device without need for intracardiac hardware placement.

41. Impedance of directional deep bran stimulation leads in subthalamic nucleus: Evaluation of variation in chronic follow up

The novel Deep Brain Stimulation (DBS) directional leads have a 1.5 mm2 surface, compared to the 6 mm2 of standard cylindrical ring leads. The lower contacts surface area physiologically implicates an increment of the impedances values and potential higher fluctuations. The aim of this study is to evaluate the impedances variation overtime in subjects who underwent to DBS surgery with a directional system. Eleven consecutive patients underwent to surgery in bilateral Subthalamic Nucleus (STN) using directional leads. At the activation visit and the subsequent visits, the impedances values were collected up to 12 months. All the patients received the best program set in terms of clinical outcomes. We collect data of more than 160 contacts. A faster impedance increase is detected in early post-operative phase with subsequent decrease over time. 97.5% of therapeutic contacts at 6 months were directional. The fluctuations of the impedances in the active directional contacts appear to be greater than in the cylindrical contacts. The use of a Directional DBS system with constant-current stimulation seems to be a proper tool to maintain the therapeutic stability.

(Invited) Stability of PEDOT:PSS Coating Under Electrical Stimulation – a Bench Study

Conductive polymers, particularly poly(3,4-ethylenedioxythiophene) (PEDOT), have attracted a good amount of interest in the past two decades as an alternative to platinum-based materials at the neural interface for electrical stimulation and recording. In addition to the reported higher charge storage and charge injection capacities, PEDOT-based coatings offer the advantages of unique physicomechanical properties, e.g., lower stiffness and a combination of electronic and ionic conductivity that could potentially create a more biomechanically compatible electrode/tissue interface. However, questions remain in terms of the long-term physical and chemical/electrochemical stability of PEDOT:PSS and whether this or related materials can be a viable alternative to platinum alloys for long-term electrical stimulation. In this bench study, the stability of PEDOT:PSS was evaluated by subjecting coated electrodes, prepared through electropolymerization in an electrolyte containing 0.01 M of EDOT and 0.1 M of NaPSS, to biphasic constant current stimulation in 0.9% saline at 37oC. The electrode potential during stimulation was measured versus a saturated calomel reference electrode (SCE) via an integrated oscilloscope. Electrochemical impedance spectroscopy (EIS) was used as a non-destructive tool to track and assess the stability and structural integrity of the coating as a function of stimulation over time. It was found that the anode potential and cathode potential of PEDOT:PSS coated electrodes continue to drift up in anodic and cathodic direction, respectively, under stimulation. More importantly, the Interpulse potential of the cathode can be driven into high anodic potential region that can cause irreversible physical and chemical changes to the coating that indicates a lack of stability with chronic use, which was confirmed by post stimulation visual observation and XPS surface analysis on the electrodes.

16-Channel biphasic current-mode programmable charge balanced neural stimulation

BackgroundNeural stimulation is an important method used to activate or inhibit action potentials of the neuronal anatomical targets found in the brain, central nerve and peripheral nerve. The neural stimulator system produces biphasic pulses that deliver balanced charge into tissue from single or multichannel electrodes. The timing and amplitude of these biphasic pulses are precisely controlled by the neural stimulator software or imbedded algorithms. Amplitude mismatch between the anodic current and cathodic current of the biphasic pulse will cause permanently damage for the neural tissues. The main goal of our circuit and layout design is to implement a 16-channel biphasic current mode programmable neural stimulator with calibration to minimize the current mismatch caused by inherent complementary metal oxide semiconductor (CMOS) manufacturing processes.MethodsThis paper presents a 16-channel constant current mode neural stimulator chip. Each channel consists of a 7-bit controllable current DAC used as sink and source current driver. To reduce the LSB quantization error and the current mismatch, an automatic calibration circuit and flow diagram is presented in this paper. There are two modes of operation of the stimulator chip—namely, stimulation mode and calibration mode. The chip also includes a digital interface used to control the stimulator parameters and calibration levels specific for each individual channel.ResultsThis stimulator Application Specific Integrated Circuit (ASIC) is designed and fabricated in a 0.18 μm High-Voltage CMOS technology that allows for ±20 V power supply. The full-scale stimulation current was designed to be at 1 mA per channel. The output current was shown to be constant throughout the timing cycles over a wide range of electrode load impedances. The calibration circuit was also designed to reduce the effect of CMOS process variation of the P-channel metal oxide semiconductor (PMOS) and N-channel metal oxide semiconductor (NMOS) devices that will result in charge delivery to have less than 0.13% error.ConclusionsA 16-channel integrated biphasic neural stimulator chip with calibration is presented in this paper. The stimulator circuit design was simulated and the chip layout was completed. The chip layout was verified using design rules check (DRC) and layout versus schematic (LVS) design check using computer aided design (CAD) software. The test results we presented show constant current stimulation with charge balance error within 0.13% least-significant-bit (LSB). This LSB error was consistent throughout a variety stimulation patterns and electrode load impedances.

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

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.

Shifting from constant-voltage to constant-current in Parkinson's disease patients with chronic stimulation.

The study aimed to evaluate safety and efficacy of shifting stimulation settings from constant-voltage (CV) to constant-current (CC) programming in patients with Parkinson's disease (PD) and chronic subthalamic nucleus deep brain stimulation (STN DBS). Twenty PD patients with chronic STN DBS set in CV programming were shifted to CC and followed for 3months; the other stimulation settings and the medication regimen remained unchanged. Side effects, motor, non-motor, executive functions, and impedance were assessed at baseline and during follow-up. No adverse events were observed at time of shifting or during CC stimulation. Motor and non-motor measures remained unchanged at follow-up despite impedance decreased. Compared to baseline, inhibition processes improved at follow-up. The shifting strategy was well tolerated and the clinical outcome was maintained with no need to adjust stimulation settings or medications notwithstanding a decrease of impedance. Improvement of inhibition processes is a finding which needed further investigation.

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery

Background ContextDuring spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. PurposeThe objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. Study DesignThis is a prospective, within-subject study. Patient SampleData from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. Outcome MeasuresThe success rates of the TES-MEP recordings from each muscle were examined. Materials and MethodsTranscranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international “10–20” system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. ResultsThe success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20–1.31]). ConclusionsThe success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

A Portable, Arbitrary Waveform, Multichannel Constant Current Electrotactile Stimulator.

In this paper, we present the design and performance of a portable, arbitrary waveform, multichannel constant current electrotactile stimulator that costs less than $30 in components. The stimulator consists of a stimulation controller and power supply that are less than half the size of a credit card and can produce ±15 mA at ±150 V. The design is easily extensible to multiple independent channels that can receive an arbitrary waveform input from a digital-to-analog converter, drawing only 0.9 W/channel (lasting 4-5 hours upon continuous stimulation using a 9 V battery). Finally, we compare the performance of our stimulator to similar stimulators both commercially available and developed in research.

Constant-Current Deep Brain Stimulation of the Globus Pallidus Internus in the Treatment of Primary Dystonia by a Novel 8-Contact (Octrode) Lead.

To evaluate bilateral constant-current globus pallidus internus (GPi) deep brain stimulation using an 8-contact lead. This prospective, open-label, single-center pilot study of 10 patients assessed the feasibility ofdelivering bilaterally constant-current GPi deep brain stimulation with a novel 8-channel lead to treat primary dystonia using standard scales as outcome measures. Patients included 4 men and 6 women with a mean age of 35.8 years ± 9.2 (range, 27-49 years). Mean age of onset was 18.5 years ± 9.1 (range, 8-35 years), and mean disease duration was 17.3 years (range, 7-27 years). All had primary dystonia (8 generalized dystonia, 1 segmental dystonia, 1 focal dystonia). The primary variable was determined as 50% reduction in dystonia symptoms from baseline to the 6-month follow-up, as defined by the Burke-Fahn-Marsden Dystonia Rating Scale. Six patients (60.0%) achieved >50% reduction in Burke-Fahn-Marsden Dystonia Rating Scale score and were classified as responders at the 6-month follow-up. Five of these 6 responders (83.3%) sustained that response through the assessment at the end of the first year. Constant-current stimulation was associated with significant improvement in pain and quality of life in all patients. Nearly 84% of the overall improvement occurred by the end of first month after stimulation onset, documenting an early response to treatment. Axial symptoms responded the best. Constant-current GPi deep brain stimulation proved safe and efficacious for treatment of primary dystonia. Motor scores improved by 54%, mostly within the first month. No phenotype-specific stimulation could be achieved, despite the capability of the new lead to stimulate specific loci within the GPi.

P152 After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats

Purpose Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. Methods These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. A Teflon-coated stainless-steel twisted-wire electrode (125 μm exposed tips; 0.5 mm tip separation) was placed in the left corpus callosum (3.0 mm anterior to bregma, 2.0 mm lateral to midline, 3.0 mm below the dural surface). The electrode position was adjusted in depth to maximize evoked field potentials at the surface of the skull (Fig. 1) Download : Download high-res image (401KB) Download : Download full-size image . Reference and ground electrodes were attached to the exposed scalp tissue and to a stereotaxic screw. To evoke field potentials in the right motor cortex, biphasic, square-wave constant current stimulation pulses with a duration of 0.1 ms and an intensity of 300 μA were delivered to the left corpus callosum at 30 s intervals using a A365 stimulus isolator. Anodal tDCS current was applied at an intensity of 250 μA for 20 min (n = 8) or 500 μA for 10 min (n = 3) using a direct current stimulator. These intensities for tDCS were based on previously reported limits (52,400 C/m2) for safe stimulation. Results Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS (Fig. 2) Download : Download high-res image (269KB) Download : Download full-size image . To induce these long-lasting effects, a sufficient duration of stimulation (20 min or more) was found to may be required rather than high stimulation intensity. Conclusion We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity. This research was supported by National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014R1A2A2A01002501).

T024 Modulation of gamma oscillations dynamics by weak electric fields

We are interested in the acute effects of weak electric fields on gamma oscillations, which is a critical neural substrate of information processing in the hippocampus. Stimulation with weak currents is known to have a relatively small effect on the firing of individual neurons. Yet, when applying stimulation during gamma activity in rodent slices, we find that the effects of fields are significantly amplified by the neuronal network. Using a computational model we demonstrate that this amplification is the result of the dynamic push and pull of the excitatory/inhibitory feedback loop, which is the hallmark of gamma oscillations. The recorded effects have a mixed spatial distribution in CA3, which is the hippocampal region with the strongest recursive feedback and the main generator of gamma activity. This recursive structure is sometimes thought to be the core processing unit for associative memories. Interestingly, when applying constant current stimulation, the enhancement of gamma activity and neuronal firing outlast the period of stimulation by several minutes, suggesting plastic effects of DC stimulation on this important associative neuronal network.

Normative data of upper limb nerve conduction studies in healthy adult population of Haryana

Background: The nerve condition velocity depends on the diameter, the degree of myelination, and internodal distance. It is also affected by physiological variables such as age, temperature, height, gender, and limb and also affected by ethnicity and food habits. Every neurophysiology laboratory needs to have its own normative data for its population required in clinical practice to identify the abnormalities. Aims and Objective: The objective of this study was to get normative data of upper limb nerve conduction in Haryana population and to compare our values with worldwide published data. Materials and Methods: This study was conducted in randomized selected 120 healthy subjects of both sexes of the general population who were between the ages of 18 and 70 years using PC based Neurostem-2 machine with silver electrode. Nerve conduction properties were evaluated for median and ulnar nerve on both sides using standard techniques of supramaximal percutaneous stimulation with a constant current stimulator and surface recording electrode for both nerves of each subject. Parameters included are distal motor latency (DML), amplitude, and conduction velocity (CV). Results: In the right median nerve, DML was 2.9 ± 0.58, the amplitude was 11.72 ± 5.22, and the CV was 52.58 ± 6.62. In the left median nerve, DML was 2.88 ± 0.61, the amplitude was 12.32 ± 5.44, and the CV was 52.48 ± 5.92. In the right ulnar nerve, DML was 2.07 ± 0.44, the amplitude was 10.02 ± 3.22, and the CV was 53.28 ± 6.62. In the left ulnar nerve, DML was 2.11 ± 0.52, the amplitude was 9.8 ± 2.88, and the CV was 52.18 ± 5.32. Conclusions: Normative conduction parameter of the median and ulnar nerve in the upper limb was established for neurophysiology laboratory of SGT Medical College, Hospital and Research Institute, Gurgaon.

A study protocol for a single-blind, randomized controlled trial of adjunctive transcranial direct current stimulation (tDCS) for chronic pain among patients receiving specialized, inpatient multimodal pain management

BackgroundAvailable treatments for chronic pain (CP) are modestly effective or associated with iatrogenic harm. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that may be an effective, adjunctive treatment to non-opioid therapies. In this randomized control trial (RCT), we compare adjunctive active versus sham tDCS among patients in a multimodal inpatient pain management program. The primary objectives of the RCT are to improve pain tolerance and subjective pain experience. Methods and designPatients admitted to the Pain Management Program at The Menninger Clinic in Houston, Texas are eligible for this trial. Eighty-four participants will be randomized (1:1) into a single-blind, 2×12 (group×time) controlled trial. A battery-powered direct and constant current stimulator (Soterix Medical Inc. 2014) delivers anodal stimulation over the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation over the right DLPFC. Active tDCS is applied by supplying a 2mA current for 20min/session over 10 sessions. Participants complete self-report and performance-based assessments on a weekly basis just prior to brain stimulation. Self-report assessments are collected via Chronic Pain Tracker version 3.6, an iPad interfaced application. The performance-based pain tolerance task is completed through the cold presser task. DiscussionInterventions with cross-symptomatic therapeutic potential are absolutely essential in the context of CP, in which psychiatric comorbidity is the norm. Modalities that can be used in tandem with evidence-based, non-opioid therapies have the potential to have a synergistic effect, resulting in increased effectiveness of what have been modestly effective treatments to date.

Neuropsychological outcomes from constant current deep brain stimulation for Parkinson's disease.

ABSTRACTObjectiveThe aim of this study was to evaluate the neurobehavioral safety of constant‐current subthalamic deep brain stimulation and to compare the neuropsychological effects of stimulation versus electrode placement alone.MethodsA total of 136 patients with Parkinson's disease underwent bilateral subthalamic device implantation in this randomized trial. Patients received stimulation either immediately after device implantation (n = 101; active stimulation) or beginning 3 months after surgery (n = 35; delayed activation control). Patients were administered neuropsychological tests before, 3, and 12 months after device implantation.ResultsNeuropsychological change in stimulation and control groups were comparable. Within‐group analyses revealed declines in category and switching verbal fluency in both groups, but only the stimulation group had letter verbal fluency and Stroop task declines. Depression symptom improvements occurred in both groups, but more often in the stimulation group. Letter fluency declines were associated with worse Parkinson's Disease Questionnaire Communication subscale scores. Baseline and 12‐month comparisons (in the combined group) revealed gains in verbal and visual delayed recall scores and improvement in depression symptoms, but decrements in verbal fluency and Stroop scores.ConclusionsConstant‐current bilateral subthalamic stimulation had a good cognitive safety profile except for decrements in verbal fluency and on the Stroop task. These abnormalities are related to device implantation, but stimulation likely had an additive effect. One year after surgery, the cognitive changes did not exert a detrimental effect on quality of life, although letter fluency declines were associated with communication dissatisfaction at 12 months. Improvement in depressive symptom severity appears dependent on stimulation and not placebo or lesion effects. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

EPV 10. Bi-frontal transcranial direct current stimulation does not modulate sleep continuity in patients with insomnia

Objective and background The most influential neurobiological model of insomnia disorder is the ‘hyperaorusal model’, which states increased level of arousal during day and nighttime as a fundamental characteristic of the disorder ( Riemann et al., 2010 ). Prior work emphasizes the crucial role of cortical activity levels and cortico-thalamic feedback in this disorder ( Nofzinger et al., 2004 ). In a prior study, our research group demonstrated that bi-frontal anodal tDCS significantly decreased total sleep time (TST) and increased cortical arousal during wakefulness as indexed by resting state EEG gamma power in healthy participants ( Frase et al., 0000 ). To further elucidate the relevance of prefrontal activity levels in insomnia disorder, we tested the hypothesis that bi-frontal cathodal tDCS results in an increase of TST by reducing cortical hyperarpousal in patients with insomnia with anodal tDCS inducing reverse effects. Methods Nineteen patients with nonorganic insomnia (13 females, 6 males, age 43.8 ± 15.1 years, 20–60 years) were included in the analysis. After adaptation to the sleep laboratory conditions, each participant underwent a baseline and three experimental nights in intervals of 3–7 days with a tDCS protocol immediately prior to polysomnography (11 pm to 7 am) according to standard procedures. The polysomnographic parameter total sleep time (TST) was defined as the main outcome parameter for of sleep continuity. Three different conditions (activation, deactivation, sham) were applied in a counterbalanced order. tDCS was delivered by a battery-driven, micro-processor-controlled constant current stimulator (Neuro-conn, Illmenau, Germany) and transferred by two pairs of electrodes (5 cm × 7 cm and 10 cm × 10 cm) covered with electrode cream positioned over FP1/FP2, respectively over P3/P4. A current of 1 mA was applied over each target electrode with a ramp up/ramp down of 30 s at the start and end of each stimulation and an interstimulusinterval (ISI) of 20 min. Results In contrast to our hypothesis, bi-frontal tDCS did not result in significant changes in sleep continuity or architecture. Analyses of subjective sleep ratings detected no differences between conditions (Repeated measures ANOVAs conducted for all three conditions separately, all p > 0.6). Discussion In contrast to our findings in healthy participants, the current results in patients with insomnia do not show differences in sleep continuity after tDCS. Instead, the sleep pattern in insomnia patients appears to be robust to cortical stimulation, which could be caused by persistant hyperarousal overriding possible tDCS-effects.

A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test.

Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson's disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson's lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way.