Conventional Deep Brain Stimulation Research Articles

Comparative Study of Robot-Assisted versus Conventional Frame-Based Deep Brain Stimulation Stereotactic Neurosurgery

Background/Aims: Technological advancements had a serious impact on the evolution of robotic systems in stereotactic neurosurgery over the last three decades and may turn robot-assisted stereotactic neurosurgery into a sophisticated alternative to purely mechanical guiding devices. Objectives: To compare robot-assisted and conventional frame-based deep brain stimulation (DBS) surgery with regard to accuracy, precision, reliability, duration of surgery, intraoperative imaging quality, safety and maintenance using a standardized setup. Methods: Retrospective evaluation of 80 consecutive patients was performed who underwent DBS surgery using either a frame-based mechanical stereotactic guiding device (n = 40) or a stereotactic robot (ROSA Brain, MedTech, Montpellier, France) (n = 40). Results: The mean accuracy of robot-assisted and conventional lead implantation was 0.76 mm (SD: 0.37 mm, range: 0.17–1.52 mm) and 1.11 mm (SD: 0.59 mm, range: 0.10–2.90 mm), respectively. We observed a statistically significant difference in accuracy (p < 0.001) when comparing lateral deviations between both modalities. Furthermore, a statistical significance was observed when investigating the proportion of values exceeding 2.00 mm between both groups (p = 0.013). In 8.75% (n = 7) of conventionally implanted leads, lateral deviations were greater than 2.0 mm. With a maximum value of 1.52 mm, this threshold was never reached during robot-guided DBS. The mean duration of DBS surgery could be reduced significantly (p < 0.001) when comparing robot-guided DBS (mean: 325.1 ± 81.6 min) to conventional lead implantation (mean: 394.8 ± 66.6 min). Conclusions: Robot-assisted DBS was shown to be superior to conventional lead implantation with respect to accuracy, precision and operation time. Improved quality control, continuous intraoperative monitoring and less manual adjustment likely contribute to the robotic system’s reliability allowing high accuracy during lead implantation despite limited experience. Hence, robot-assisted lead implantation can be considered an appropriate and reliable alternative to purely mechanical devices.

Computational Modeling of Ultrasonic Subthalamic Nucleus Stimulation.

To explore the potential of ultrasonic modulation of plateau-potential generating subthalamic nucleus neurons (STN), by modeling their interaction with continuous and pulsed ultrasonic waves. A computational model for ultrasonic stimulation of the STN is created by combining the Otsuka-model with the bilayer sonophore model. The neuronal response to continuous and pulsed ultrasonic waves is computed in parallel for a range of frequencies, duty cycles, pulse repetition frequencies, and intensities. Ultrasonic intensity in continuous-wave stimulation determines the firing pattern of the STN. Three observed spiking modes in order of increasing intensity are low frequency spiking, high frequency spiking with significant spike-frequency and spike-amplitude adaptation, and a silenced mode. Continuous-wave stimulation has little capability to manipulate the saturated spiking rate in the high frequency spiking mode. In contrast, STN firing rates induced by pulsed ultrasound insonication will saturate to the pulse repetition frequency with short latencies, for sufficiently large intensity and repetition frequency. Computational results show that the activity of plateau-potential generating STN can be modulated by selection of the stimulus parameters. Low intensities result in repetitive firing, while higher intensities silence the STN. Pulsed ultrasonic stimulation results in a shorter saturation latency and is able to modulate spiking rates. Stimulation or suppresion of the STN is important in the treatment of Parkinson's disease, e.g., in deep brain stimulation. This explorative study on ultrasonic modulation of the STN, could be a step in the direction of minimally invasive alternatives to conventional deep brain stimulation.

Parkinsonian Tremor Detection from Subthalamic Nucleus Local Field Potentials for Closed-Loop Deep Brain Stimulation.

Deep Brain Stimulation (DBS) is a widely used therapy to ameliorate symptoms experienced by patients with Parkinson's Disease (PD). Conventional DBS is continuously ON even though PD symptoms fluctuate over time leading to undesirable side-effects and high energy requirements. This study investigates the use of a Iogistic regression-based classifier to identify periods when PD patients have rest tremor exploiting Local Field Potentials (LFPs) recorded with DBS electrodes implanted in the Subthalamic Nucleus in 7 PD patients (8 hemispheres). Analyzing 36.1 minutes of data with a 512 milliseconds non-overlapping window, the classification accuracy was well above chance-level for all patients, with Area Under the Curve (AUC) ranging from 0.67 to 0.93. The features with the most discriminative ability were, in descending order, power in the 31-45 Hz, 5-7 Hz, 21-30 Hz, 46-55 Hz, and 56-95 Hz frequency bands. These results suggest that using a machine learning-based classifier, such as the one proposed in this study, can form the basis for on-demand DBS therapy for PD tremor, with the potential to reduce side-effects and lower battery consumption.

High-resolution local field potentials measured with deep brain stimulation arrays

Objective. Local field potential (LFP) recordings along a deep brain stimulation (DBS) lead can provide useful feedback for titrating DBS therapy. However, conventional DBS leads with four cylindrical macroelectrodes likely undersample the spatial distribution of sinks and sources in a given brain region. In this study, we investigated the spectral power and spatial feature sizes of LFP activity in non-human primate subthalamic nucleus and globus pallidus using chronically implanted 32-channel directional DBS arrays. Approach. Subthalamic nucleus and globus pallidus LFP signals were recorded from directional DBS arrays in the resting state and during a reach-and-retrieval task in two non-human primates in naïve and parkinsonian conditions. LFP recordings were compared amongst bipolar pairs of electrodes using individual and grouped electrode configurations, with the latter mimicking the cylindrical macroelectrode configurations used in current clinical LFP recordings. Main results. Recordings from these DBS arrays showed that (1) beta oscillations have spatial ‘fingerprints’ in the subthalamic nucleus and globus pallidus, and (2) that these oscillations were muted when grouping electrode contacts together to create cylindrical macroelectrodes similar in relative dimension to those used clinically. Further, these maps depended on parkinsonian condition and whether the subject was resting or performing a motor task. Significance. Development of future closed-loop DBS therapies that rely on LFP feedback will benefit from implanting DBS arrays with electrode sizes and spacings that are more consistent with the dimensions of oscillatory sinks and sources within the brain.

Haloperidol\u2013induced catalepsy is ameliorated by deep brain stimulation of the inferior colliculus

Deep brain stimulation (DBS) has evolved as a promising alternative treatment for Parkinson’s disease (PD), but the underlying mechanisms remain poorly understood. Moreover, conventional DBS protocols targeted at basal ganglia sites can turn out completely ineffective for some PD patients, warranting the search for alternative targets. The inferior colliculus (IC) is a midbrain auditory relay station involved in sensorimotor processes. High-frequency 2500 Hz electrical stimulation of the IC elicits escape behaviour and interferes with haloperidol-induced catalepsy in rats, a state reminiscent of Parkinsonian akinesia, but clinical implication is limited since the protocol is aversive. However, typical DBS stimulation frequencies range between 20–180 Hz. We therefore tested the effects of a low-frequency 30 Hz-DBS protocol on haloperidol-induced catalepsy and aversive behaviour in rats. We show that low-frequency 30 Hz-DBS targeted at the IC strongly ameliorates haloperidol-induced catalepsy without any evidence of stimulation-induced escape behaviour. Furthermore, 30 Hz-DBS of the IC produced no place avoidance in a place conditioning paradigm and induced no anxiety-related behaviour on the elevated plus maze, indicating that the protocol has no aversive or anxiogenic side effects. Our findings provide first evidence that the IC can serve as an alternative, non-conventional DBS target.

Adaptive Brain Stimulation for Movement Disorders.

Deep brain stimulation (DBS) has markedly changed how we treat movement disorders including Parkinson's disease (PD), dystonia, and essential tremor (ET). However, despite its demonstrable clinical benefit, DBS is often limited by side effects and partial efficacy. These limitations may be due in part to the fact that DBS interferes with both pathological and physiological neural activities. DBS could, therefore, be potentially improved were it applied selectively and only at times of enhanced pathological activity. This form of stimulation is known as closed-loop or adaptive DBS (aDBS). An aDBS approach has been shown to be superior to conventional DBS in PD in primates using cortical neuronal spike triggering and in humans employing local field potential biomarkers. Likewise, aDBS studies for essential and Parkinsonian tremor are advancing and show great promise, using both peripheral or central sensing and stimulation. aDBS has not yet been trialed in dystonia and yet exciting and promising biomarkers suggest it could be beneficial here too. In this chapter, we will review the existing literature on aDBS in movement disorders and explore potential biomarkers and stimulation algorithms for applying aDBS in PD, ET, and dystonia.

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

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.

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

BackgroundConventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach. ObjectivesThe current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS. MethodsThis pilot study compared biphasic pulses (BiP) versus conventional DBS pulses (ClinDBS). Eleven ET subjects with clinically optimized ventralis intermedius nucleus DBS were enrolled. Objective measures were obtained over 3 h while ON BiP stimulation. ResultsThere was observed benefit in the Fahn-Tolosa Tremor Rating Scale (TRS) for BiP conditions when compared to the DBS off condition and to ClinDBS setting. Total TRS scores during the DBS OFF condition (28.5 IQR = 24.5–35.25) were significantly higher than the other time points. Following active DBS, TRS improved to (20 IQR = 13.8–24.3) at ClinDBS setting and to (16.5 IQR = 12–20.75) at the 3 h period ON BiP stimulation (p = 0.001). Accelerometer recordings revealed improvement in tremor at rest (χ2 = 16.1, p = 0.006), posture (χ2 = 15.9, p = 0.007) and with action (χ2 = 32.1, p=<0.001) when comparing median total scores at ClinDBS and OFF DBS conditions to 3 h ON BiP stimulation. There were no adverse effects and gait was not impacted. ConclusionBiP was safe, tolerable and effective on the tremor symptoms when tested up to 3 h. This study demonstrated the feasibility of applying a novel DBS waveform in the clinic setting. Larger prospective studies with longer clinical follow-up will be required.

Effects of Subthalamic and Nigral Stimulation on Gait Kinematics in Parkinson’s Disease

Conventional subthalamic deep brain stimulation for Parkinson’s disease (PD) presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG). Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr) area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN) stimulation. Here, we aimed to characterize the differential effect of STN or SNr stimulation on kinematic gait parameters. We analyzed biomechanical parameters during unconstrained over ground walking in 12 PD patients with subthalamic deep brain stimulation and FOG. Patients performed walking in three therapeutic conditions: (i) Off stimulation, (ii) STN stimulation (alone), and (iii) SNr stimulation (alone). SNr stimulation was achieved by stimulating the most caudal contact of the electrode. We recorded gait using three sensors (each containing a tri-axial accelerometer, gyroscope, and magnetometer) attached on both left and right ankle, and to the lumbar spine. STN stimulation improved both the spatial features (stride length, stride length variability) and the temporal parameters of gait. SNr stimulation improved temporal parameters of gait (swing time asymmetry). Correlation analysis suggested that patients with more medial localization of the SNr contact associated with a stronger regularization of gait. These results suggest that SNr stimulation might support temporal regularization of gait integration.

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

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.

Postoperative neuroimaging analysis of DRT deep brain stimulation revision surgery for complicated essential tremor

BackgroundWe report a patient who received conventional bilateral deep brain stimulation of the ventral intermediate nucleus of thalamus (Vim) for the treatment of medication refractory essential tremor (ET). After initial beneficial effects, therapeutic efficacy was lost due to a loss of control of his proximal trunkal and extremity tremor. The patient received successful diffusion tensor magnetic resonance imaging fiber tractographic (DTI FT)-assisted DBS revision surgery targeting the dentato-rubro-thalamic tract (DRT) in the subthalamic region (STR).ObjectiveTo report the concept of DTI FT-assisted DRT DBS revision surgery for ET and to show sophisticated postoperative neuroimaging analysis explaining improved symptom control.MethodsAnalysis was based on preoperative DTI sequences and postoperative helical computed tomography (hCT). Leads, stimulation fields, and fibers were reconstructed using commercial software systems (Elements, Brainlab AG, Feldkirchen, Germany; GUIDE XT, Boston Scientific Corp., Boston, MA, USA).ResultsThe patient showed immediate and sustained tremor improvement after DTI FT-assisted revision surgery. Analysis of the two implantations (electrode positions in both instances) revealed a lateral and posterior shift in the pattern of modulation of the cortical fiber pathway projection after revision surgery as compared to initial implantation, explaining a more efficacious stimulation.ConclusionsOur work underpins a possible superiority of direct targeting approaches using advanced neuroimaging technologies to perform personalized DBS surgery. The evaluation of DBS electrode positions with the herein-described neuroimaging simulation technologies will likely improve targeting and revision strategies. Direct targeting with DTI FT-assisted approaches in a variety of indications is the focus of our ongoing research.

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

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.

Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review.

Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor fluctuations and dyskinesia when other treatments have not given satisfactory results. Our objective was to summarize the present evidence base for LCIG therapy through a systematic review of the literature. Studies were identified from the PubMed and EMBASE databases up to 12 March 2016 using the following search terms: Parkinson disease, duodopa, levodopa/carbidopa intestinal gel, levodopa-carbidopa intestinal gel, LCIG, l-dopa infusion, levodopa infusion, duodenal l-dopa infusion, and duodenal levodopa infusion. Data extraction focused on whether LCIG therapy improves motor and non-motor outcomes as well as quality of life in PD patients compared with conventional therapy, apomorphine infusion, or deep brain stimulation. Randomized controlled trials (RCTs) and observational studies, with or without a control group, that included more than ten patients were included. The search was limited to peer-reviewed articles published in full in the English language and involving humans. Infusion of LCIG reduced "off" time, increased "on" time without increasing troublesome dyskinesias, and improved quality of life in three RCTs (one double-blind). Open-label follow-ups confirm these findings. The data evaluating long-term efficacy and safety are still limited. The quality of evidence that LCIG is effective in reducing fluctuating motor symptoms and improving quality of life is moderate. Quality of evidence for reduction of non-motor symptoms is very low. Safety issues mainly relate to the intestinal infusion system. LCIG might be a useful treatment option in PD patients with severe motor fluctuations.

An external portable device for adaptive deep brain stimulation (aDBS) clinical research in advanced Parkinson's Disease

Compared to conventional deep brain stimulation (DBS) for patients with Parkinson's Disease (PD), the newer approach of adaptive DBS (aDBS), regulating stimulation on the basis of the patient's clinical state, promises to achieve better clinical outcomes, avoid adverse-effects and save time for tuning parameters. A remaining challenge before aDBS comes into practical use is to prove its feasibility and its effectiveness in larger groups of patients and in more ecological conditions.We developed an external portable aDBS system prototype designed for clinical testing in freely-moving PD patients with externalized DBS electrodes. From a single-channel bipolar artifact-free recording, it analyses local field potentials (LFPs), during ongoing DBS for tuning stimulation parameters, independent from the specific feedback algorithm implemented. We validated the aDBS system in vitro, by testing both its sensing and closed-loop stimulation capabilities, and then tested it in vivo, focusing on the sensing capabilities.By applying the aDBS system prototype in a patient with PD, we provided evidence that it can track levodopa and DBS-induced LFP spectral power changes among different patient's clinical states.Our system, intended for testing LFP-based feedback strategies for aDBS, should help understanding how and whether aDBS therapy works in PD and indicating future technical and clinical advances.

Optimal control of directional deep brain stimulation in the parkinsonian neuronal network

The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson’s disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson’s disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia–thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation of 32 different contacts with optimal stimulation intensity and immediately after the stimulation, respectively. These can reveal regional differences in pathological activity within STN nucleus. It is shown that in line with the experimental results directional steering stimulation can induce the low-amplitude LFP which implies the occurrence of desynchronizing regime, as well as the distribution of DF can locate at the 13–40 Hz of beta frequency range. Hopefully, the obtained results can provide theoretical evidences in exploring pathophysiologic activity of brain.

Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease.

The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders. To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example. A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders. The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets. Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with drugs.

Adaptive deep brain stimulation in patients with Parkinson’s disease: phase II clinical trial preliminary results

Background: Emerging evidence now suggests that conventional deep brain stimulation (cDBS) for the treatment of Parkinson’s disease (PD) could be optimized using adaptive deep brain stimulation (aDBS) continuously supplies the stimulator with new settings obtained by analyzing control variable related to the patient’s current clinical state. A reliable control variable is subthalamic local field potential (LFP) activity recorded from the stimulating electrode itself.Objective: We designed a randomized, double-blind, cross-over clinical trial to compare the efficacy, the safety and the amount of charge delivered (TEED) of aDBS versus cDBS using an external dual (cDBS or aDBS) mode portable device controlled by LFPs.Patients and methods: Seven patients were randomly assigned to aDBS or cDBS as first treatment and blinded to the treatment. Both aDBS and cDBS were administered for 2 hours consecutively, during which the patient was assessed every 30 minutes, by a blinded investigator, through the UPDRS III and the Rush dyskinesia scales. The experimental sessions were also video-recorded in order to analyze any treatment related Adverse Events (AE).Results: Over the 2 hour of stimulation the patients exhibited a reduction of dyskinesias during aDBS compared to cDBS maintaining the same UPDRS III score. There were no treatment related AE (severe, moderate and mild) both during aDBS and cDBS. The TEED during aDBS was 70% less than cDBS (p < 0.03).Conclusions: Preliminary data showed that aDBS is safe and well tolerated in PD patients and decrease the amount of TEED, thus obtaining a reduction of dyskinesias. Our work should help understand how aDBS therapy works in PD and indicate future technical and clinical advances. Background: Emerging evidence now suggests that conventional deep brain stimulation (cDBS) for the treatment of Parkinson’s disease (PD) could be optimized using adaptive deep brain stimulation (aDBS) continuously supplies the stimulator with new settings obtained by analyzing control variable related to the patient’s current clinical state. A reliable control variable is subthalamic local field potential (LFP) activity recorded from the stimulating electrode itself. Objective: We designed a randomized, double-blind, cross-over clinical trial to compare the efficacy, the safety and the amount of charge delivered (TEED) of aDBS versus cDBS using an external dual (cDBS or aDBS) mode portable device controlled by LFPs. Patients and methods: Seven patients were randomly assigned to aDBS or cDBS as first treatment and blinded to the treatment. Both aDBS and cDBS were administered for 2 hours consecutively, during which the patient was assessed every 30 minutes, by a blinded investigator, through the UPDRS III and the Rush dyskinesia scales. The experimental sessions were also video-recorded in order to analyze any treatment related Adverse Events (AE). Results: Over the 2 hour of stimulation the patients exhibited a reduction of dyskinesias during aDBS compared to cDBS maintaining the same UPDRS III score. There were no treatment related AE (severe, moderate and mild) both during aDBS and cDBS. The TEED during aDBS was 70% less than cDBS (p < 0.03). Conclusions: Preliminary data showed that aDBS is safe and well tolerated in PD patients and decrease the amount of TEED, thus obtaining a reduction of dyskinesias. Our work should help understand how aDBS therapy works in PD and indicate future technical and clinical advances.

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

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

74. Adaptive Deep Brain Stimulation (ADBS) tested clinically in a patient with advanced Parkinson Disease

Conventional deep brain stimulation DBS (cDBS) could be optimized by adapting the stimulation to the patient’s clinical state marked by a control variable (i.e. adaptive DBS). Local field potentials (LFPs) recorded from DBS electrodes correlate with the patient‘s clinical state and can be a reliable control variable for aDBS. We developed an external portable aDBS device controlled by LFPs and we present its clinical assessment in a freely moving PD patient. The 5th and the 6th day after the DBS electrodes implant in the subthalamic nucleus, the patient, after the standard antiparkinsonian medication, underwent 2 h of cDBS and 2 h of aDBS, respectively. The patient was not aware of the DBS type. The motor state was evaluated by a blinded neurologist through the UPDRS motor scale (part III), and dyskinesia scale (Rush filming protocol). Whereas the UPDRS III score was the same during aDBS and cDBS, the dyskinesias were less severe by 57.59% during aDBS compared to cDBS. The aDBS device controlled better the motor fluctuations than cDBS, reducing dyskinesias. This study represents a proof of aDBS application for PD.

Implanted rechargeable electroencephalography (EEG) device

Electroencephalography (EEG) and deep brain stimulation (DBS), as specific instrument and tool, respectively, for reading and changing the electrical activities of the human brain, are milestones in the history of neuroscience and brain research. Although scientists have gone very far in exploring the brain, the mechanisms of many neurological diseases and therapies are not clear yet. Therefore, an implanted rechargeable EEG device, adding the recording function to conventional DBS to make it not only a therapy device but a scientific research tool has been developed. The EEG performance of the device is good compared with the SynAmps2 of NeuroScan. Radio-frequency (RF) communication at 403 MHz is used for data transmission, which has a high speed and long transmission distance and enables mass quantity data transmission. A rechargeable battery is used for power supply, making the system life longer and lowering the requirement of low-power design. This device is a good platform for neuroscience research by being implanted in animal models of different nervous system disorders or patients with diseases such as Parkinson's disease (PD). The recorded data will help to better understand the brain and the mechanisms of brain disorders and also help to optimise clinical therapy.