Cognitive Effects of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease with GBA1 Pathogenic Variants.

Genetic subtyping of patients with Parkinson's disease (PD) may assist in predicting the cognitive and motor outcomes of subthalamic deep brain stimulation (STN-DBS). Practical questions were recently raised with the emergence of new data regarding suboptimal cognitive outcomes after STN-DBS in individuals with PD associated with pathogenic variants in glucocerebrosidase gene (GBA1-PD). However, a variety of gaps and controversies remain. (1) Does STN-DBS truly accelerate cognitive deterioration in GBA1-PD? If so, what is the clinical significance of this acceleration? (2) How should the overall risk-to-benefit ratio of STN-DBS in GBA1-PD be established? (3) If STN-DBS has a negative effect on cognition in GBA1-PD, how can this effect be minimized? (4) Should PD patients be genetically tested before STN-DBS? (5) How should GBA1-PD patients considering STN-DBS be counseled? We aim to summarize the currently available relevant data and detail the gaps and controversies that exist pertaining to these questions. In the absence of evidence-based data, all authors strongly agree that clinicians should not categorically deny DBS to PD patients based solely on genotype (GBA1 status). We suggest that PD patients considering DBS may be offered genetic testing for GBA1, where available and feasible, so the potential risks and benefits of STN-DBS can be properly weighed by both the patient and clinician. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Genetic Etiology of Parkinson's Disease Does Not Robustly Affect Subthalamic Physiology.

BACKGROUND: It is unknown whether Parkinson's disease (PD) genetic heterogeneity, leading to phenotypic and pathological variability, is also associated with variability in the unique PD electrophysiological signature. Such variability might have practical implications for adaptive deep brain stimulation (DBS). OBJECTIVE: The aim of our work was to study the electrophysiological activity in the subthalamic nucleus (STN) of patients with PD with pathogenic variants in different disease-causing genes. METHODS: Electrophysiological data from participants with negative genetic tests were compared with those from GBA, LRRK2, and PRKN-PD. RESULTS: We analyzed data from 93 STN trajectories (GBA-PD: 28, LRRK2-PD: 22, PARK-PD: 10, idiopathic PD: 33) of 52 individuals who underwent DBS surgery. Characteristics of ß oscillatory activity in the dorsolateral motor part of the STN were similar for patients with negative genetic tests and for patients with different forms of monogenic PD. CONCLUSIONS: The genetic heterogeneity in PD is not associated with electrophysiological differences. Therefore, similar adaptive DBS algorithms would be applicable to genetically heterogeneous patient populations. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Basal ganglia beta oscillations during sleep underlie Parkinsonian insomnia.

Sleep disorders are among the most debilitating comorbidities of Parkinson's disease (PD) and affect the majority of patients. Of these, the most common is insomnia, the difficulty to initiate and maintain sleep. The degree of insomnia correlates with PD severity and it responds to treatments that decrease pathological basal ganglia (BG) beta oscillations (10-17 Hz in primates), suggesting that beta activity in the BG may contribute to insomnia. We used multiple electrodes to record BG spiking and field potentials during normal sleep and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in nonhuman primates. MPTP intoxication resulted in severe insomnia with delayed sleep onset, sleep fragmentation, and increased wakefulness. Insomnia was accompanied by the onset of nonrapid eye movement (NREM) sleep beta oscillations that were synchronized across the BG and cerebral cortex. The BG beta oscillatory activity was associated with a decrease in slow oscillations (0.1-2 Hz) throughout the cortex, and spontaneous awakenings were preceded by an increase in BG beta activity and cortico-BG beta coherence. Finally, the increase in beta oscillations in the basal ganglia during sleep paralleled decreased NREM sleep, increased wakefulness, and more frequent awakenings. These results identify NREM sleep beta oscillation in the BG as a neural correlate of PD insomnia and suggest a mechanism by which this disorder could emerge.

Asleep DBS under ketamine sedation: Proof of concept.

BACKGROUND: Deep brain stimulation (DBS) is commonly and safely performed for selective Parkinson's disease patients. Many centers perform DBS lead positioning exclusively under local anesthesia, to optimize brain microelectrode recordings (MER) and testing of stimulation-related therapeutic and side effects. These measures enable physiological identification of the DBS borders and subdomains based on electrophysiological properties like firing rates and patterns, intra-operative evaluation of therapeutic window, and improvement of lead placement accuracy. Nevertheless, due to the challenges of awake surgery, some centers use sedation or general anesthesia, despite the distortion of discharge properties and interference with clinical testing, resulting in potential impact on surgical outcomes. Thus, there is a need for a novel anesthesia regimen that enables sedation without compromising intra-operative monitoring. OBJECTIVE: This open-label study investigates the use of low-dose ketamine for conscious sedation during microelectrode recordings and lead positioning in subthalamic nucleus (STN) DBS for Parkinson's disease patients. METHODS: Three anesthetic regimens were retrospectively compared in 38 surgeries (74 MER trajectories, 5962 recording sites) across three DBS centers: 1) Interleaved propofol-ketamine (PK), 2) Interleaved propofol-awake (PA), and 3) Fully awake (AA). RESULTS: All anesthesia regimens achieved satisfactory MER. Detection of STN borders and subdomains by expert electrophysiologist was similar between the groups. Electrophysiological signature of the STN under ketamine was not inferior to either control group. All patients completed stimulation testing. CONCLUSIONS: This study supports a low-dose ketamine anesthesia regimen for DBS which allows microelectrode recordings and stimulation testing that are not inferior to those conducted under awake and propofol-awake regimens and may optimize patient experience. A prospective double-blind study that would also compare patients' satisfaction level and clinical outcome should be performed to confirm these findings.

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Desynchronization of slow oscillations in the basal ganglia during natural sleep.

Slow oscillations of neuronal activity alternating between firing and silence are a hallmark of slow-wave sleep (SWS). These oscillations reflect the default activity present in all mammalian species, and are ubiquitous to anesthesia, brain slice preparations, and neuronal cultures. In all these cases, neuronal firing is highly synchronous within local circuits, suggesting that oscillation-synchronization coupling may be a governing principle of sleep physiology regardless of anatomical connectivity. To investigate whether this principle applies to overall brain organization, we recorded the activity of individual neurons from basal ganglia (BG) structures and the thalamocortical (TC) network over 70 full nights of natural sleep in two vervet monkeys. During SWS, BG neurons manifested slow oscillations (∼0.5 Hz) in firing rate that were as prominent as in the TC network. However, in sharp contrast to any neural substrate explored thus far, the slow oscillations in all BG structures were completely desynchronized between individual neurons. Furthermore, whereas in the TC network single-cell spiking was locked to slow oscillations in the local field potential (LFP), the BG LFP exhibited only weak slow oscillatory activity and failed to entrain nearby cells. We thus show that synchrony is not inherent to slow oscillations, and propose that the BG desynchronization of slow oscillations could stem from its unique anatomy and functional connectivity. Finally, we posit that BG slow-oscillation desynchronization may further the reemergence of slow-oscillation traveling waves from multiple independent origins in the frontal cortex, thus significantly contributing to normal SWS.

Movement context modulates neuronal activity in motor and limbic-associative domains of the human parkinsonian subthalamic nucleus.

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement ('None-Go' task, n = 7, 28 recording sites); second, pressing a button after every tone ('All-Go' task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones ('Go-NoGo' task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation.

Theta-alpha oscillations characterize emotional subregion in the human ventral subthalamic nucleus.

BACKGROUND: Therapeutic outcomes of STN-DBS for movement and psychiatric disorders depend on electrode location within the STN. Electrophysiological and functional mapping of the STN has progressed considerably in the past years, identifying beta-band oscillatory activity in the dorsal STN as a motor biomarker. It also has been suggested that STN theta-alpha oscillations, involved in impulse control and action inhibition, have a ventral source. However, STN local field potential mapping of motor, associative, and limbic areas is often limited by poor spatial resolution. OBJECTIVES: Providing a high-resolution electrophysiological map of the motor, associative and limbic anatomical sub-areas of the subthalamic nucleus. METHODS: We have analyzed high-spatial-resolution STN microelectrode electrophysiology recordings of PD patients (n = 303) that underwent DBS surgery. The patients' STN intraoperative recordings of spiking activity (933 electrode trajectories) were combined with their imaging data (n = 83 patients, 151 trajectories). RESULTS: We found a high theta-alpha (7-10 Hz) oscillatory area, located near the STN ventromedial border in 29% of the PD patients. Theta-alpha activity in this area has higher power and lower central frequency in comparison to theta-alpha activity in more dorsal subthalamic areas. When projected on the DISTAL functional atlas, the theta-alpha oscillatory area overlaps with the STN limbic subarea. CONCLUSIONS: We suggest that theta-alpha oscillations can serve as an electrophysiological marker for the ventral subthalamic nucleus limbic subarea. Therefore, theta-alpha oscillations can guide optimal electrode placement in neuropsychiatric STN-DBS procedures and provide a reliable biomarker input for future closed-loop DBS device. © 2019 International Parkinson and Movement Disorder Society.

[DEEP BRAIN STIMULATION FOR OBSESSIVE COMPULSIVE DISORDER: CASE REPORT OF THE FIRST OCD PATIENT IN ISRAEL].

INTRODUCTION: Treatment-resistant obsessive-compulsive disorder (OCD) is considered a severe psychiatric disorder that causes severe functional decline. In the past, these patients were treated by selective ablation of neuronal pathways related to the pathophysiology of OCD. Deep brain stimulation is an effective and safe treatment alternative that enables reversible changes in neural circuits and reduces OCD symptoms. In this paper we present the outcome of a treatment-resistant OCD patient who underwent deep brain stimulation procedure for the first time in Israel. The patient has achieved a significant decline in OCD symptoms as well as improvement in personal and social functioning. The discussion focuses on methods to implement deep brain stimulation for OCD patients in Israel.

Longer ß oscillatory episodes reliably identify pathological subthalamic activity in Parkinsonism.

BACKGROUND: The efficacy of deep brain stimulation (DBS) - primarily of the subthalamic nucleus (STN) - for advanced Parkinson's disease (PD) is commonly attributed to the suppression of pathological synchronous ß oscillations along the cortico-thalamo-basal ganglia network. Conventional continuous high-frequency DBS indiscriminately influences pathological and normal neural activity. The DBS protocol would therefore be more effective if stimulation was only applied when necessary (closed-loop adaptive DBS). OBJECTIVES AND METHODS: Our study aimed to identify a reliable biomarker of the pathological neuronal activity in parkinsonism that could be used as a trigger for adaptive DBS. To this end, we examined the oscillatory features of paired spiking activities recorded in three distinct nodes of the basal ganglia network of 2 African green monkeys before and after induction of parkinsonism (by MPTP intoxication). RESULTS: Parkinsonism-related basal ganglia ß oscillations consisted of synchronized time-limited episodes, rather than a continuous stretch, of ß oscillatory activity. Episodic basal ganglia ß oscillatory activity, although prolonged in parkinsonism, was not necessarily pathological given that short ß episodes could also be detected in the healthy state. Importantly, prolongation of the basal ganglia ß episodes was more pronounced than their intensification in the parkinsonian state-especially in the STN. Hence, deletion of longer ß episodes was more effective than deletion of stronger ß episodes in reducing parkinsonian STN synchronized oscillatory activity. CONCLUSIONS: Prolonged STN ß episodes are pathological in parkinsonism and can be used as optimal trigger for future adaptive DBS applications. © 2018 International Parkinson and Movement Disorder Society.

Parallel processing of internal and external feedback in the spinocerebellar system of primates.

Cerebellar control of voluntary movements is achieved by the integration of external and internal feedback information to adjust and correct properly ongoing actions. In the forelimb of primates, rostral-spinocerebellar tract (RSCT) neurons are thought to integrate segmental, descending, and afferent sources and relay upstream a compound signal that contains both an efference copy of the spinal-level motor command and the state of the periphery. We tested this hypothesis by implanting stimulating electrodes in the superior cerebellar peduncle and recording the activity of cervical spinal neurons in primates. To dissociate motor commands and proprioceptive signals, we used a voluntary wrist task and applied external perturbations to the movement. We identified a large group of antidromically activated RSCT neurons located in deep dorsal sites and a smaller fraction of postsynaptically activated (PSA) cells located in intermediate and ventral laminae. RSCT cells received sensory input from broad, proximally biased receptive fields (RFs) and were not affected by applied wrist perturbations. PSA cells received sensory information from distal RFs and were more strongly related to active and passive movements. The anatomical and functional properties of RSCT and PSA cells suggest that descending signals converging on PSA cells contribute to both motor preparation and motor control. In parallel, RSCT neurons relay upstream an integrated signal that encodes the state of working muscles and can contribute to distal-to-proximal coordination of action. Thus the rostral spinocerebellar system sends upstream an efference copy of the motor command but does not signal abrupt errors in the performed movement.NEW & NOTEWORTHY Cerebellar coordination of voluntary movements relies on integrating feedback information to update motor output. With the use of a novel protocol, we identified spinal neurons constituting the ascending and descending components of the forelimb spinocerebellar system in behaving primates. The data suggest that descending information contributes to both motor preparation and execution, whereas ascending information conveys the spinal level motor command, such that internal and external feedback is relayed through parallel pathways.

Local vs. volume conductance activity of field potentials in the human subthalamic nucleus.

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300-9,000 Hz) and field potentials (3-100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson's disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms.NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms.

Stop! border ahead: Automatic detection of subthalamic exit during deep brain stimulation surgery.

BACKGROUND: Microelectrode recordings along preplanned trajectories are often used for accurate definition of the subthalamic nucleus (STN) borders during deep brain stimulation (DBS) surgery for Parkinson's disease. Usually, the demarcation of the STN borders is performed manually by a neurophysiologist. The exact detection of the borders is difficult, especially detecting the transition between the STN and the substantia nigra pars reticulata. Consequently, demarcation may be inaccurate, leading to suboptimal location of the DBS lead and inadequate clinical outcomes. METHODS: We present machine-learning classification procedures that use microelectrode recording power spectra and allow for real-time, high-accuracy discrimination between the STN and substantia nigra pars reticulata. RESULTS: A support vector machine procedure was tested on microelectrode recordings from 58 trajectories that included both STN and substantia nigra pars reticulata that achieved a 97.6% consistency with human expert classification (evaluated by 10-fold cross-validation). We used the same data set as a training set to find the optimal parameters for a hidden Markov model using both microelectrode recording features and trajectory history to enable real-time classification of the ventral STN border (STN exit). Seventy-three additional trajectories were used to test the reliability of the learned statistical model in identifying the exit from the STN. The hidden Markov model procedure identified the STN exit with an error of 0.04 ± 0.18 mm and detection reliability (error < 1 mm) of 94%. CONCLUSIONS: The results indicate that robust, accurate, and automatic real-time electrophysiological detection of the ventral STN border is feasible. © 2016 International Parkinson and Movement Disorder Society.

Anesthesia reduces discharge rates in the human pallidum without changing the discharge rate ratio between pallidal segments.

Classical rate models of basal ganglia circuitry associate discharge rate of the globus pallidus external and internal segments (GPe, GPi respectively) solely with dopaminergic state and predict an inverse ratio between the discharge rates of the two pallidal segments. In contrast, the effects of other rate modulators such as general anesthesia (GA) on this ratio have been ignored. To respond to this need, we recorded the neuronal activity in the GPe and GPi in awake and anesthetized human patients with dystonia (57 and 53 trajectories respectively) and in awake patients with Parkinson's disease (PD, 16 trajectories) undergoing deep brain stimulation procedures. This triad enabled us to dissociate pallidal discharge ratio from general discharge modulation. An automatic offline spike detection and isolation quality system was used to select 1560 highly isolated units for analysis. The mean discharge rate in the GPi of awake PD patients was dramatically higher than in awake dystonia patients although the firing rate in the GPe was similar. Firing rates in dystonic patients under anesthesia were lower in both nuclei. Surprisingly, in all three groups, GPe firing rates were correlated with firing rates in the ipsilateral GPi. Thus, the firing rate ratio of ipsilateral GPi/GPe pairs was similar in awake and anesthetized patients with dystonia and significantly higher in PD. We suggest that pallidal activity is modulated by at least two independent processes: dopaminergic state which changes the GPi/GPe firing rate ratio, and anesthesia which modulates firing rates in both pallidal nuclei without changing the ratio between their firing rates.

Long non-coding RNA and alternative splicing modulations in Parkinson's leukocytes identified by RNA sequencing.

The continuously prolonged human lifespan is accompanied by increase in neurodegenerative diseases incidence, calling for the development of inexpensive blood-based diagnostics. Analyzing blood cell transcripts by RNA-Seq is a robust means to identify novel biomarkers that rapidly becomes a commonplace. However, there is lack of tools to discover novel exons, junctions and splicing events and to precisely and sensitively assess differential splicing through RNA-Seq data analysis and across RNA-Seq platforms. Here, we present a new and comprehensive computational workflow for whole-transcriptome RNA-Seq analysis, using an updated version of the software AltAnalyze, to identify both known and novel high-confidence alternative splicing events, and to integrate them with both protein-domains and microRNA binding annotations. We applied the novel workflow on RNA-Seq data from Parkinson's disease (PD) patients' leukocytes pre- and post- Deep Brain Stimulation (DBS) treatment and compared to healthy controls. Disease-mediated changes included decreased usage of alternative promoters and N-termini, 5'-end variations and mutually-exclusive exons. The PD regulated FUS and HNRNP A/B included prion-like domains regulated regions. We also present here a workflow to identify and analyze long non-coding RNAs (lncRNAs) via RNA-Seq data. We identified reduced lncRNA expression and selective PD-induced changes in 13 of over 6,000 detected leukocyte lncRNAs, four of which were inversely altered post-DBS. These included the U1 spliceosomal lncRNA and RP11-462G22.1, each entailing sequence complementarity to numerous microRNAs. Analysis of RNA-Seq from PD and unaffected controls brains revealed over 7,000 brain-expressed lncRNAs, of which 3,495 were co-expressed in the leukocytes including U1, which showed both leukocyte and brain increases. Furthermore, qRT-PCR validations confirmed these co-increases in PD leukocytes and two brain regions, the amygdala and substantia-nigra, compared to controls. This novel workflow allows deep multi-level inspection of RNA-Seq datasets and provides a comprehensive new resource for understanding disease transcriptome modifications in PD and other neurodegenerative diseases.

Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent medication was reduced on average by 67% (range 15-88). Patients were poorly compliant with PD diaries, and these did not yield useful information. The minor deterioration in quality-of-life scores (Parkinson's Disease Questionnaire-39, Quality of Life Enjoyment and Satisfaction Questionnaire) with CC stimulation were not statistically significant. Two measures of depression (Hamilton Rating Scale D17, Quick Inventory of Depressive Symptomatology - Self-Report) showed a nonsignificant lower score (less depression) with CC stimulation, but a third (Beck Depression Inventory) showed equivalence. Cognitive testing (Mini Mental State Examination) and emotional processing (Montreal Affective Voices) were equivalent for CC and CV. Conclusion: CC STN DBS is safe. For equivalent motor efficacy, no significant difference could be identified between CC and CV stimulation for nonmotor evaluations in PD patients 2 years after surgery. © 2015 S. Karger AG, Basel.

The rationale driving the evolution of deep brain stimulation to constant-current devices.

OBJECTIVE: Deep brain stimulation (DBS) is an effective therapy for the treatment of a number of movement and neuropsychiatric disorders. The effectiveness of DBS is dependent on the density and location of stimulation in a given brain area. Adjustments are made to optimize clinical benefits and minimize side effects. Until recently, clinicians would adjust DBS settings using a voltage mode, where the delivered voltage remained constant. More recently, a constant-current mode has become available where the programmer sets the current and the stimulator automatically adjusts the voltage as impedance changes. METHODS: We held an expert consensus meeting to evaluate the current state of the literature and field on constant-current mode versus voltage mode in clinical brain-related applications. RESULTS/CONCLUSIONS: There has been little reporting of the use of constant-current DBS devices in movement and neuropsychiatric disorders. However, as impedance varies considerably between patients and over time, it makes sense that all new devices will likely use constant current.