Parkinsonian Subthalamic Nucleus Research Articles

Exploring gait-related neural activity recorded from the subthalamic nucleus in Parkinson Disease

Exploring gait-related neural activity recorded from the subthalamic nucleus in Parkinson Disease

Blepharospasm Secondary to Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson Disease: Clinical Characteristics and Management Outcomes.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with motor symptoms of Parkinson disease but can be complicated by disabling blepharospasm and apraxia of eyelid opening (ALO). Currently, there is no clear consensus on optimal management, and addressing these issues is further hindered by systemic morbidity and resistance to treatments. We aim to describe the different phenotypes of these eyelid movement disorders, to report our management approach and patient responses to treatment. A retrospective case series of all patients with blepharospasm/ALO secondary to STN-DBS that were treated at a tertiary center between 2011 and 2020. Data collected included date of Parkinson diagnosis, date of DBS surgery, date of development of blepharospasm/ALO symptoms, STN-DBS stimulation settings, and treatment given. Patients' symptoms before and after treatment were measured using the blepharospasm disability index and Jankovic Rating Scale. Five patients were identified with eyelid movement disorders secondary to STN-DBS. All patients had moderate-to-severe symptoms at presentation. Four patients received periocular botulinum toxin injections. Three patients underwent surgery in the form of frontalis suspension or direct brow lift with or without upper lid blepharoplasty. All reported an improvement in symptoms following treatment. A multimodality, patient-specific approach is required in the treatment of blepharospasm/ALO secondary to STN-DBS. Botulinum toxin injections can be effective, but patients may require surgery if toxin treatment alone becomes ineffective. Tailoring treatment to individual needs can result in a measurable improvement in symptoms.

Early brain imaging changes and its influence on electrode impedance after implantation of 3.0 T MRI-compatible deep brain stimulation system in Parkinson's disease subthalamic nucleus

Objective: To analyze the imaging changes of in the early period after subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD) and its impact on electrode impedance by the application of 3.0T MRI-compatible devices. Methods: A retrospective analysis was performed for the data of 43 PD patients who underwent 3.0T MRI-compatible STN-DBS surgery from October 2022 to April 2023 at the First Affiliated Hospital of USTC(Anhui Provincial Hospital), including 27 males and 16 females, aged 43-68 (56±5) years. All patients underwent postoperative 3.0T MRI, CT scans,and impedance measurements 1 week postoperatively.Fifteen patients underwent 3.0T MRI and impedance measurements 1 month postoperatively. The differences in impedance of electrode contacts before and after the 3.0T MRI scans were compared. The occurrence of peri-lead cerebral edema (PLE) in patients was analyzed, as well as the differences in PLE detection rates between the two imaging methods, and the differences in the incidence and volume of PLE at different microelectrode recordings, the occurrence and detection of postoperative PLE, and different microelectrode recording (MER) times and different time nodes were compared. The correlation between electrode impedance and the volume of edema around the nucleus was analyzed. Results: All 43 patients successfully underwent surgery, with a total of 86 electrodes implanted. There was no significant difference in electrode impedance values before and after the 3.0T MRI examinations at 1 week and 1 month postoperatively. The PLE detection rate with 3.0T MRI was 95.12%(39/43), which is significantly higher than that of CT imaging 17.07% (7/43)(χ2=50.705, P<0.001). One week after surgery, the incidence and volume of PLE were higher in the multiple MER group compared with the single MER group, but the difference was not statistically significant. The volume of PLE [M(Q1, Q3) 0 (0, 1.211) cm3] at 1 month was significantly smaller than that at 1 week [0.243 (0, 2.914) cm3] (Z=-3.408, P=0.001). The impedance of electrode contacts within 1 month postoperatively showed a trend of initial decrease followed by an increase, which was negatively correlated with SE volume(r=-0.317, P=0.014). Conclusions: The application of 3.0T MRI-compatible DBS devices in the surgical treatment of PD patients improves the accuracy of early postoperative imaging assessment. The electrode impedance is more stable as the edema around the nucleus subsided at 1 month after surgery, which is suitable for the first program control.

Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region

Electrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson’s disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n = 3) or non-directional (n = 1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6 and 7.4 ms after a stimulus pulse). Using these features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson’s disease with DBS therapy.

Simultaneous PET/fMRI revealed increased motor area input to subthalamic nucleus in Parkinson's disease.

Invasive electrophysiological recordings in patients with Parkinson's disease (PD) are extremely difficult for cross-sectional comparisons with healthy controls. Noninvasive approaches for identifying information flow between the motor area and the subthalamic nucleus (STN) are critical for evaluation of treatment strategy. We aimed to investigate the direction of the cortical-STN hyperdirect pathway using simultaneous 18F-FDG-PET/functional magnetic resonance imaging (fMRI). Data were acquired during resting state on 34 PD patients and 25 controls. The ratio of standard uptake value for PET images and the STN functional connectivity (FC) maps for fMRI data were generated. The metabolic connectivity mapping (MCM) approach that combines PET and fMRI data was used to evaluate the direction of the connectivity. Results showed that PD patients exhibited both increased FDG uptake and STN-FC in the sensorimotor area (PFDR < 0.05). MCM analysis showed higher cortical-STN MCM value in the PD group (F = 6.63, P = 0.013) in the left precentral gyrus. There was a high spatial overlap between the increased glucose metabolism and increased STN-FC in the sensorimotor area in PD. The MCM approach further revealed an exaggerated cortical input to the STN in PD, supporting the precentral gyrus as a target for treatment such as the repetitive transcranial magnetic stimulation.

Dopaminergic Modulation of Spectral and Spatial Characteristics of Parkinsonian Subthalamic Nucleus Beta Bursts.

In Parkinson’s disease (PD), subthalamic nucleus (STN) beta burst activity is pathologically elevated. These bursts are reduced by dopamine and deep brain stimulation (DBS). Therefore, these bursts have been tested as a trigger for closed-loop DBS. To provide better targeted parameters for closed-loop stimulation, we investigate the spatial distribution of beta bursts within the STN and if they are specific to a beta sub-band. Local field potentials (LFP) were acquired in the STN of 27 PD patients while resting. Based on the orientation of segmented DBS electrodes, the LFPs were classified as anterior, postero-medial, and postero-lateral. Each recording lasted 30 min with (ON) and without (OFF) dopamine. Bursts were detected in three frequency bands: ±3 Hz around the individual beta peak frequency, low beta band (lBB), and high beta band (hBB). Medication reduced the duration and the number of bursts per minute but not the amplitude of the beta bursts. The burst amplitude was spatially modulated, while the burst duration and rate were frequency dependent. Furthermore, the hBB burst duration was positively correlated with the akinetic-rigid UPDRS III subscore. Overall, these findings on differential dopaminergic modulation of beta burst parameters suggest that hBB burst duration is a promising target for closed-loop stimulation and that burst parameters could guide DBS programming.

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.

The characteristics of pallidal low-frequency and beta bursts could help implementing adaptive brain stimulation in the parkinsonian and dystonic internal globus pallidus

IntroductionAdaptive deep brain stimulation (aDBS) has been applied in Parkinson's disease (PD), based on the presence of brief high-amplitude beta (13–35 Hz) oscillation bursts in the subthalamic nucleus (STN), which correlate with symptom severity. Analogously, average low-frequency (LF) oscillatory power (4–12 Hz) in the internal globus pallidus (GPi) correlates with dystonic symptoms and might be a suitable physiomarker for aDBS in dystonia. Characterization of pallidal bursts could facilitate the implementation of aDBS in the GPi of PD and dystonia patients. Objective and methodsWe aimed to describe the bursting behaviour of LF and beta oscillations in a cohort of five GPi-DBS PD patients and compare their amplitude and length with those of a cohort of seven GPi-DBS dystonia, and six STN-DBS PD patients (n electrodes = 34). Furthermore, we used the information obtained to set up aDBS and test it in the GPi of both a dystonia and a PD patient (n = 2), using either LF (dystonia) or beta oscillations (PD) as feedback signals. ResultsLF and beta oscillations in the dystonic and parkinsonian GPi occur as phasic, short-lived bursts, similarly to the parkinsonian STN. The amplitude profile of such bursts, however, differed significantly. Dystonia showed higher LF burst amplitudes, while PD presented higher beta burst amplitudes. Burst characteristics in the parkinsonian GPi and STN were similar. Furthermore, aDBS applied in the GPi was feasible and well tolerated in both diseases. ConclusionPallidal LF and beta burst amplitudes have different characteristics in PD and dystonia. The presence of increased burst amplitudes could be employed as feedback for GPi-aDBS.

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

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 β 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). 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). Parkinsonism-related basal ganglia β oscillations consisted of synchronized time-limited episodes, rather than a continuous stretch, of β oscillatory activity. Episodic basal ganglia β oscillatory activity, although prolonged in parkinsonism, was not necessarily pathological given that short β episodes could also be detected in the healthy state. Importantly, prolongation of the basal ganglia β episodes was more pronounced than their intensification in the parkinsonian state-especially in the STN. Hence, deletion of longer β episodes was more effective than deletion of stronger β episodes in reducing parkinsonian STN synchronized oscillatory activity. Prolonged STN β episodes are pathological in parkinsonism and can be used as optimal trigger for future adaptive DBS applications. © 2018 International Parkinson and Movement Disorder Society.

Radiosurgical Subthalamic Nucleotomy.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the reference technique in Parkinson's disease (PD) at different stages of complications. Some patients cannot afford DBS due to anticoagulation or comorbidities or due to pecuniary reasons. Radiosurgery is a minimally invasive stereotactic technique, with no craniotomy and subsequently no risk of bleeding or infection. Its good safety efficacy profile has been established in the treatment of tremor, and the postoperative care issues are simple with a much shorter hospital stay (mean 48 h). The application of radiosurgery to STN target in PD as an alternative to DBS is being debated. The lesion of the STN is presumed to induce hemiballism. Experimental works suggest a potential lower risk of hemiballism in animal models of PD. However, radiofrequency ablation of the STN is associated with a significant rate of severe dyskinesia, sometimes permanent and severe enough to request salvage pallidotomies. The positive experience of VIM radiosurgery in tremor and its capacity to create precise, accurate and well-controlled lesions provides reasonable rationale for the evaluation of this technique when applied to STN in PD. Preliminary results till date have shown the absence of severe permanent dyskinesia. Prospective controlled trials are mandatory to evaluate the safety efficacy of this technique in PD.

Speech changes induced by deep brain stimulation of the subthalamic nucleus in Parkinson disease: involvement of the dentatorubrothalamic tract

OBJECTIVE Patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) often develop a deterioration in speech performance, but there is no clear consensus on the specific effects seen or the mechanism involved and little description of the impact of DBS on conversational speech. Furthermore, there has been no fiber tract connectivity analysis to identify the structures potentially modulated by DBS to cause such deficits. The main objective of this study was to quantify spontaneous speech performance and identify potential involvement of the dentatorubrothalamic tract (DRTt) in patients who underwent STN DBS, because this tract has been implicated in speech deterioration. METHODS Spontaneous speech samples were obtained with STN DBS in both on and off modes in 35 patients with PD and assessed across multiple domains. Diffusion tensor imaging tractography seeded from the therapeutic DBS contacts was performed to identify the fiber tracts involved and, specifically, the DRTt. The position of active electrode contacts was assessed relative to that of the STN. RESULTS Fifteen patients with akinetic-rigid (AR) PD and 20 with tremor-dominant (TD) PD subtypes were identified. In the AR-PD subgroup of patients, in whom there was DRTt involvement, 71% demonstrated much better overall speech and largely improved or unchanged fluency in the DBS-off condition. In patients with TD PD with DRTt involvement, 50% demonstrated better overall speech in the off condition, and equivocal results regarding improved or worsened fluency were found. When there was minimal DRTt involvement, 75% of patients with AR PD had better overall speech in the DBS-on condition and better or minimal fluency changes. Similarly, 83% of patients with TD PD with minimal DRTt involvement had better or minimal overall speech and fluency changes in the on condition. More medially placed left electrode contacts were associated with more DRTt involvement in 77% of patients (10 of 13). CONCLUSIONS To the authors' knowledge, this is the first study to have investigated a specific fiber tract involved in STN DBS in different subtypes of PD relative to its impact on spontaneous speech. At optimal therapeutic programming of STN DBS, overall spontaneous speech and fluency were affected more negatively in patients with AR PD than in those with TD PD when there was DRTt involvement. After fiber tract analysis and modeling, it was found that medially positioned left electrode contacts more often involved fibers of the DRTt. If possible, avoidance of the DRTt by using active electrode contacts that are positioned less medially, specifically in patients with AR PD, might result in less speech deterioration.

Phase-amplitude coupling, an indication of bursting in parkinsonism, is masked by periodic pulses.

Interactions between neural oscillations in the brain have been observed in many structures including the hippocampus, amygdala, motor cortex, and basal ganglia. In this study, one popular approach for quantifying oscillation interactions was considered: phase-amplitude coupling. The goals of the study were to use simulations to examine potential causes of elevated phase-amplitude coupling in parkinsonism, to compare simulated parkinsonian signals with recorded local field potentials from animal models of parkinsonism, to investigate possible relationships between increased bursting in parkinsonian single cells and elevated phase-amplitude coupling, and to uncover potential noise and artifact effects. First, a cell model that integrates incremental input currents and fires at realistic voltage thresholds was modified to allow control of stochastic parameters related to firing and burst rates. Next, the input currents and distribution of integration times were set to reproduce firing patterns consistent with those from parkinsonian subthalamic nucleus cells. Then, local field potentials were synthesized from the output of multiple simulated cells with varying degrees of synchronization and compared with subthalamic nucleus recordings from animal models of parkinsonism. The results showed that phase-amplitude coupling can provide important information about underlying neural activity. In particular, signals synthesized from synchronized bursting neurons showed increased oscillatory interactions similar to those observed in parkinsonian animals. Additionally, changes in bursting parameters such as the intraburst rate, the mean interburst period, and the amount of synchronization between neurons influenced the phase-amplitude coupling in predictable ways. Finally, simulation results revealed that small periodic signals can have a surprisingly large masking effect on phase-amplitude coupling.

Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease.

OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery.

Higher neuronal discharge rate in the motor area of the subthalamic nucleus of Parkinsonian patients.

In Parkinson's disease, pathological synchronous oscillations divide the subthalamic nucleus (STN) of patients into a dorsolateral oscillatory region and ventromedial nonoscillatory region. This bipartite division reflects the motor vs. the nonmotor (associative/limbic) subthalamic areas, respectively. However, significant topographic differences in the neuronal discharge rate between these two STN subregions in Parkinsonian patients is still controversial. In this study, 119 STN microelectrode trajectories (STN length > 2 mm, mean = 5.32 mm) with discernible oscillatory and nonoscillatory regions were carried on 60 patients undergoing deep brain stimulation surgery for Parkinson's disease. 2,137 and 2,152 multiunit stable signals were recorded (recording duration > 10 s, mean = 21.25 s) within the oscillatory and nonoscillatory STN regions, respectively. Spike detection and sorting were applied offline on every multiunit stable signal using an automatic method with systematic quantification of the isolation quality (range = 0-1) of the identified units. In all, 3,094 and 3,130 units were identified in the oscillatory and nonoscillatory regions, respectively. On average, the discharge rate of better-isolated neurons (isolation score > 0.70) was higher in the oscillatory region than the nonoscillatory region (44.55 ± 0.87 vs. 39.97 ± 0.77 spikes/s, N = 665 and 761, respectively). The discharge rate of the STN neurons was positively correlated to the strength of their own and their surrounding 13- to 30-Hz beta oscillatory activity. Therefore, in the Parkinsonian STN, beta oscillations and higher neuronal discharge rate are correlated and coexist in the motor area of the STN compared with its associative/limbic area.

Parameter identification for a local field potential driven model of the Parkinsonian subthalamic nucleus spike activity

Several models, with various degrees of complexity have been proposed to model the neuronal activity from different parts of the human brain. We have shown before that various modeling approaches, including a Hammerstein–Wiener (H–W) model, can be used to predict the spike trains from a deep nucleus, the subthalamic nucleus, using the underlying local field potentials. In this article, we present, in depth, the various choices one has to make, and the limitations that they introduce, during the H–W model parameter identification process. From a segment of the recorded data, which contains information about the spike times of a single neuron, we identify and extract the model parameters. We then use those parameters to numerically simulate the spike timing, the rhythm and the inter-spike intervals for the rest of the recording. To assess how well the model fits to the measured data we combine measures of spike train synchrony, namely the Victor–Purpura distance and the Gaussian similarity measure, with time-scale independent train distances. We show that a wise combination of metrics results in models that predict the spikes with temporal accuracy ranging, on average, from 53% to more than 80%, depending on the number of the neurons’ spikes recorded. The model’s prediction is adequate for estimating accurately the spike rhythm. Quantitative results establish the model’s validity as a simple yet biologically plausible model of the spike activity recorded from a deep nucleus inside the human brain.

Proliferation of External Globus Pallidus-Subthalamic Nucleus Synapses following Degeneration of Midbrain Dopamine Neurons

The symptoms of Parkinson's disease (PD) are related to changes in the frequency and pattern of activity in the reciprocally connected GABAergic external globus pallidus (GPe) and glutamatergic subthalamic nucleus (STN). In idiopathic and experimental PD, the GPe and STN exhibit hypoactivity and hyperactivity, respectively, and abnormal synchronous rhythmic burst firing. Following lesion of midbrain dopamine neurons, abnormal STN activity emerges slowly and intensifies gradually until it stabilizes after 2-3 weeks. Alterations in cellular/network properties may therefore underlie the expression of abnormal firing. Because the GPe powerfully regulates the frequency, pattern, and synchronization of STN activity, electrophysiological, molecular, and anatomical measures of GPe-STN transmission were compared in the STN of control and 6-hydroxydopamine-lesioned rats and mice. Following dopamine depletion: (1) the frequency (but not the amplitude) of mIPSCs increased by ∼70%; (2) the amplitude of evoked IPSCs and isoguvacine-evoked current increased by ∼60% and ∼70%, respectively; (3) mRNA encoding α1, β2, and γ2 GABA(A) receptor subunits increased by 15-30%; (4) the density of postsynaptic gephyrin and γ2 subunit coimmunoreactive structures increased by ∼40%, whereas the density of vesicular GABA transporter and bassoon coimmunoreactive axon terminals was unchanged; and (5) the number of ultrastructurally defined synapses per GPe-STN axon terminal doubled with no alteration in terminal/synapse size or target preference. Thus, loss of dopamine leads, through an increase in the number of synaptic connections per GPe-STN axon terminal, to substantial strengthening of the GPe-STN pathway. This adaptation may oppose hyperactivity but could also contribute to abnormal firing patterns in the parkinsonian STN.

Localization of the subthalamic nucleus in Parkinson disease using multiunit activity

BackgroundRefinement of the subthalamic nucleus (STN) coordinates using intraoperative microelectrode recordings (MER) is routinely performed during deep brain stimulation (DBS) surgeries in Parkinson disease (PD). The commonly used criteria for electrophysiological localization of the STN are qualitative. The goal of this study was to validate quantitative STN detection algorithm (QD) derived from the multi-unit activity in a prospective setting. MethodsTen PD patients underwent STN DBS surgery. The MUA was obtained by removing large spikes close to microelectrode using wavelet method and integrating the 500–2000Hz band in the power spectral density. The qualitative intraoperative mapping of the STN using MER (IOM) versus QD was compared using Bland–Altman and Pearson's correlation analysis. ResultsThe clinical efficacy was confirmed in all subjects. The mean difference between IOM and QD of the dorsal/ventral border was 0.31±0.84/0.44±0.47mm. Using Bland–Altman statistic, only 2/36 (5.6%) differences (one for the dorsal border and one for the ventral border) were out of ±2 sd line of measurement differences. Correlation between dorsal border/ventral border positions obtained by IOM and QD was 0.79, p<0.0001/0.91, p<0.0001. ConclusionBoth methods are in reasonable agreement and are strongly correlated. The QD gives objective coordinates of the STN borders at high precision and may be more accurate than IOM. Prospective blinded comparative studies where the DBS leads will be placed using either QD or IOM are warranted.

Prediction of the Timing and the Rhythm of the Parkinsonian Subthalamic Nucleus Neural Spikes Using the Local Field Potentials

In this paper, we discuss the use of a nonlinear cascade model to predict the subthalamic nucleus spike activity from the local field potentials recorded in the motor area of the nucleus of Parkinson's disease patients undergoing deep brain stimulation. We use a segment of appropriately selected and processed data recorded from five nuclei to acquire the information of the spike timing and rhythm of a single neuron and estimate the model parameters. We then use the rest of each recording to assess the model's accuracy in predicting spike timing, rhythm, and interspike intervals. We show that the cumulative distribution function (CDF) of the predicted spikes remains inside the 95% confidence interval of the CDF of the recorded spikes. By training the model appropriately, we prove its ability to provide quite accurate predictions for multiple-neuron recordings as well, and we establish its validity as a simple yet biologically plausible model of the intranuclear spike activity recorded from Parkinson's disease patients.

The Need for a Multifactorial Approach to Raise the Standard in Deep Brain Stimulation Reporting

Deep brain stimulation (DBS) has been demonstrated to be an effective therapeutic strategy for the treatment of pharmacologically refractory Parkinson disease (PD) ( 1. Kleiner-Fisman G Herzog J Fisman DN et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord. 2006; 21: S290-S304 Crossref Scopus (761) Google Scholar ). Since its renaissance in 1987 ( 2. Benabid AL Pollak P Louveau A Henry S de Rougemont J Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987; 50: 344-346 PubMed Google Scholar , 3. Hariz MI Blomstedt P Zrinzo L Deep brain stimulation between 1947 and 1987: the untold story. Neurosurg Focus. 2010; 29: E1 Crossref Scopus (150) Google Scholar ), it has become widely accepted in the movement disorders community with more than 33,000 patients currently implanted. Targets have evolved from the ventral intermediate nucleus of the thalamus ( 2. Benabid AL Pollak P Louveau A Henry S de Rougemont J Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987; 50: 344-346 PubMed Google Scholar , 4. Benabid AL Pollak P Gervason C et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991; 337: 403-406 Abstract PubMed Scopus (1393) Google Scholar ) to the globus pallidus internus ( 5. Siegfried J Lippitz B Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery. 1994; 35 (discussion 1129–1130): 1126-1129 Crossref PubMed Scopus (409) Google Scholar ), subsequently to the subthalamic nucleus (STN) ( 6. Pollak P Benabid AL Gross C et al. [Effects of the stimulation of the subthalamic nucleus in Parkinson disease]. Rev Neurol (Paris). 1993; 149: 175-176 PubMed Google Scholar ), and recently to the pedunculopontine nucleus ( 7. Stefani A Lozano AM Peppe A et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain. 2007; 130: 1596-1607 Crossref PubMed Scopus (636) Google Scholar ). While debate exists with respect to the optimal therapeutic target ( 8. Okun MS Foote KD Subthalamic nucleus vs globus pallidus interna deep brain stimulation, the rematch: will pallidal deep brain stimulation make a triumphant return?. Arch Neurol. 2005; 62: 533-536 Crossref PubMed Scopus (64) Google Scholar , 9. Minguez-Castellanos A Escamilla-Sevilla F Pallidal vs subthalamic deep brain stimulation for Parkinson disease: winner and loser or a sharing of honors?. Arch Neurol. 2005; 62 (author reply 1643): 1642-1643 Crossref Google Scholar ), DBS of STN is the most common surgical intervention for PD ( 10. Benabid AL Chabardes S Mitrofanis J Pollak P Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol. 2009; 8: 67-81 Abstract Full Text Full Text PDF PubMed Scopus (971) Google Scholar ). DBS of the STN has resulted in substantial motor improvements and often leads to a significant reduction in levodopa administration ( 11. Molinuevo JL Valldeoriola F Tolosa E et al. Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol. 2000; 57: 983-988 Crossref PubMed Scopus (191) Google Scholar ). Now that these major advances in motor function have been achieved, the apparent limbic side-effects of DBS have come into greater focus ( 12. Okun MS Green J Saben R Gross R Foote KD Vitek JL Mood changes with deep brain stimulation of STN and GPi: results of a pilot study. J Neurol Neurosurg Psychiatry. 2003; 74: 1584-1586 Crossref PubMed Scopus (93) Google Scholar ).

Effect of deep brain stimulation of the subthalamic nucleus upon the contralateral subthalamic nucleus in Parkinson disease

High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an effective treatment of idiopathic Parkinson disease (PD). Exactly how HFS works remains unclear. Although HFS of the STN is most effective in improving contralateral motor functions, clinical studies have shown bilateral beneficial effects suggesting that unilateral STN HFS affects both ipsilateral and contralateral basal ganglia networks. In this study we evaluated the effect of STN HFS upon the contralateral STN in 14 PD subjects. The neural recordings were done during stereotaxic neurosurgery for implantation of deep brain stimulation electrodes in the second STN. Neuronal activity of the STN was analyzed before and during two minutes of HFS. There was a significant increase in the multiunit spiking activity of the STN during HFS in the contralateral STN. Our study provides direct electrophysiological evidence that the STN HFS is associated with increased activity of the contralateral STN. These findings suggest that increased STN output underlies therapeutic mechanisms of action of HFS.