Beta oscillatory activity in the subthalamic nucleus and its relation to dopaminergic response in Parkinson's disease

Recent studies suggest that beta (15-30 Hz) oscillatory activity in the subthalamic nucleus (STN) is dramatically increased in Parkinson's disease (PD) and may interfere with movement execution. Dopaminergic medications decrease beta activity and deep brain stimulation (DBS) in the STN may alleviate PD symptoms by disrupting this oscillatory activity. Depth recordings from PD patients have demonstrated beta oscillatory neuronal and local field potential (LFP) activity in STN, although its prevalence and relationship to neuronal activity are unclear. In this study, we recorded both LFP and neuronal spike activity from the STN in 14 PD patients during functional neurosurgery. Of 200 single- and multiunit recordings 56 showed significant oscillatory activity at about 26 Hz and 89% of these were coherent with the simultaneously recorded LFP. The incidence of neuronal beta oscillatory activity was significantly higher in the dorsal STN (P = 0.01) and corresponds to the significantly increased LFP beta power recorded in the same region. Of particular interest was a significant positive correlation between the incidence of oscillatory neurons and the patient's benefit from dopaminergic medications, but not with baseline motor deficits off medication. These findings suggest that the degree of neuronal beta oscillatory activity is related to the magnitude of the response of the basal ganglia to dopaminergic agents rather than directly to the motor symptoms of PD. The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population.     

Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.     

High frequency stimulation of the subthalamic nucleus evokes striatal dopamine release in a large animal model of human DBS neurosurgery

Subthalamic nucleus deep brain stimulation (STN DBS) ameliorates motor symptoms of Parkinson's disease, but the precise mechanism is still unknown. Here, using a large animal (pig) model of human STN DBS neurosurgery, we utilized fast-scan cyclic voltammetry in combination with a carbon-fiber microelectrode (CFM) implanted into the striatum to monitor dopamine release evoked by electrical stimulation at a human DBS electrode (Medtronic 3389) that was stereotactically implanted into the STN using MRI and electrophysiological guidance. STN electrical stimulation elicited a stimulus time-locked increase in striatal dopamine release that was both stimulus intensity- and frequency-dependent. Intensity-dependent (1–7 V) increases in evoked dopamine release exhibited a sigmoidal pattern attaining a plateau between 5 and 7 V of stimulation, while frequency-dependent dopamine release exhibited a linear increase from 60 to 120 Hz and attained a plateau thereafter (120–240 Hz). Unlike previous rodent models of STN DBS, optimal dopamine release in the striatum of the pig was obtained with stimulation frequencies that fell well within the therapeutically effective frequency range of human DBS (120–180 Hz). These results highlight the critical importance of utilizing a large animal model that more closely represents implanted DBS electrode configurations and human neuroanatomy to study neurotransmission evoked by STN DBS. Taken together, these results support a dopamine neuronal activation hypothesis suggesting that STN DBS evokes striatal dopamine release by stimulation of nigrostriatal dopaminergic neurons.     

Gait and postural instability in Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus

In late stage Parkinson's disease (PD), medical treatment may not control the symptoms adequately, and the patient may become eligible for bilateral high frequency deep brain stimulation (DBS) in the subthalamic nucleus (STN). The effect of STN DBS on gait and postural instability is not always as predictable as the effect on clinical symptoms tremor, rigidity and bradykinesia. This may relate to the type of gait disorder or the stimulating electrode localization in the STN. We sought to evaluate the effect of STN DBS on gait performance during overground walking and gait initiation--assessed with 3D optokinetic movement analyses--and to compare the DBS effect with stimulation site localized on peri-operative MRI. The stimulation sites were grouped according to STN borders visualised on pre-operative MRI, and the active stimulation site was compared with clinical improvement and gait parameters. STN DBS is associated with improved movement amplitude while movement duration may be unaffected by both disease and stimulation. This may imply an improvement primarily on hypokinesia including gait hypokinesia.     

Further validation of actigraphy for sleep studies

STUDY OBJECTIVES: Actigraphy is generally compared to polysomnography (PSG), which has been considered the gold standard for sleep studies. The objective of the present study was to evaluate the concordance between PSG and two previously proposed algorithms (Cole et al, 1992; Sadeh et al, 1994) to analyze actigraphic recordings. The minute-by-minute agreement rate was evaluated through calculation of sensitivity, specificity, and accuracy. Regarding the sleep parameters, the concordance was performed through the Bland and Altman technique. DESIGN: A night of adaptation to the sleep laboratory followed by simultaneous polysomnographic and actigraphic recordings throughout the night. PARTICIPANTS: 21 healthy volunteers. SETTING: A sleep laboratory INTERVENTIONS: None. RESULTS: Ninety-one percent of all PSG epochs were correctly identified by both algorithms, and this accuracy is reasonably satisfactory. The actigraphy was a sensitive method, with values of 99% and 97% for Cole's and Sadeh's algorithms, respectively. However, actigraphy had a low specificity: 34% and 44% for Cole's and Sadeh's algorithms, respectively. The Bland and Altman technique showed that actigraphy systematically overestimated Sleep Latency, Total Sleep Time and Sleep Efficiency while it underestimated Intermittent Awakenings. CONCLUSIONS: The results of this study show the utility of actigraphy as a useful method for assessment of sleep, despite its limitations regarding identification of waking epochs during sleep. The Bland and Altman concordance technique was revealed to be a powerful tool to evaluate how well actigraphy agreed with polysomnography. This technique, combined with calculations of sensitivity and specificity, appears to be the most adequate procedure for the assessment of concordance.     

Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation

The subthalamic nucleus (STN) is the most common target for the treatment of Parkinson's disease (PD) with deep brain stimulation (DBS). DBS of the globus pallidus internus (GPi) is also effective in the treatment of PD. The output fibers of the GPi that form the lenticular fasciculus pass in close proximity to STN DBS electrodes. In turn, both STN projection neurons and GPi fibers of passage represent possible therapeutic targets of DBS in the STN region. We built a comprehensive computational model of STN DBS in parkinsonian macaques to study the effects of stimulation in a controlled environment. The model consisted of three fundamental components: 1) a three-dimensional (3D) anatomical model of the macaque basal ganglia, 2) a finite element model of the DBS electrode and electric field transmitted to the tissue medium, and 3) multicompartment biophysical models of STN projection neurons, GPi fibers of passage, and internal capsule fibers of passage. Populations of neurons were positioned within the 3D anatomical model. Neurons were stimulated with electrode positions and stimulation parameters defined as clinically effective in two parkinsonian monkeys. The model predicted axonal activation of STN neurons and GPi fibers during STN DBS. Model predictions regarding the degree of GPi fiber activation matched well with experimental recordings in both monkeys. Only axonal activation of the STN neurons showed a statistically significant increase in both monkeys when comparing clinically effective and ineffective stimulation. Nonetheless, both neural targets may play important roles in the therapeutic mechanisms of STN DBS.     

Single pulse stimulation of the human subthalamic nucleus facilitates the motor cortex at short intervals

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). The mechanism is poorly understood. High-frequency STN DBS has been reported to affect motor cortex excitability in a complex way, but the timing between STN stimuli and changes in motor cortical (M1) excitability has not been investigated. We examined the time course of changes in motor cortical excitability following single pulse STN DBS. We studied 14 PD patients with implanted DBS electrodes in the STN, 2 patients with electrodes in internal globus pallidus (GPi), and 1 patient with an electrode in the sensory thalamus. Transcranial magnetic stimulation (TMS) was delivered to the M1 ipsilateral to the DBS with induced currents either in the anterior-posterior direction in the brain to evoke indirect (I) waves or in the lateral-medial direction to activate corticospinal axons directly. Single pulse stimulation through the DBS contacts preceded the TMS by 0-10 ms. Surface EMG was recorded from the contralateral first dorsal interosseous muscle. Three milliseconds after STN stimulation, the motor evoked potential (MEP) amplitudes produced by anterior-posterior current were significantly larger than control responses, while the responses to lateral-medial currents were unchanged. Similar facilitation also occurred after GPi stimulation, but not with thalamic stimulation. Single pulse STN stimulation facilitates the M1 at short latencies. The possible mechanisms include antidromic excitation of the cortico-STN fibers or transmission through the basal ganglia-thalamocortical pathway.     

Calibrating actigraphy to improve sleep efficiency estimates

Actigraphy (ACT) can enhance treatment for insomnia by providing objective estimates of sleep efficiency; however, only two studies have assessed the accuracy of actigraphy‐based estimates of sleep efficiency (ACT‐SE) in sleep‐disordered samples studied at home. Both found poor correspondence with polysomnography‐based estimates (PSG‐SE). The current study tested that concordance in a third sample and piloted a method for improving ACT‐SE. Participants in one of four diagnostic categories (panic disorder, post‐traumatic stress disorder, comorbid post‐traumatic stress and panic disorder and controls without sleep complaints) underwent in‐home recording of sleep using concurrent ambulatory PSG and actigraphy. Precisely synchronized PSG and ACT recordings were obtained from 41 participants. Sleep efficiency was scored independently using conventional methods, and ACT‐SE/PSG‐SE concordance examined. Next, ACT data recorded initially at 0.5 Hz were resampled to 30‐s epochs and rescaled on a per‐participant basis to yield optimized concordance between PSG‐ and ACT‐based sleep efficiency estimates. Using standard scoring of ACT, the correlation between ACT‐SE and PSG‐SE across participants was statistically significant (r = 0.35, P < 0.025), although ACT‐SE failed to replicate a main effect of diagnosis. Individualized calibration of ACT against a night of PSG yielded a significantly higher correlation between ACT‐SE and PSG‐SE (r = 0.65, P < 0.001; z = 1.692, P = 0.0452, one‐tailed) and a significant main effect of diagnosis that was highly correspondent with the effect on PSG‐SE. ACT‐based estimates of sleep efficiency in sleep‐disordered patients tested at home can be improved significantly by calibration against a single night of concurrent PSG.     

Machine‐learning‐derived sleep–wake staging from around‐the‐ear electroencephalogram outperforms manual scoring and actigraphy

Quantification of sleep is important for the diagnosis of sleep disorders and sleep research. However, the only widely accepted method to obtain sleep staging is by visual analysis of polysomnography (PSG), which is expensive and time consuming. Here, we investigate automated sleep scoring based on a low‐cost, mobile electroencephalogram (EEG) platform consisting of a lightweight EEG amplifier combined with flex‐printed cEEGrid electrodes placed around the ear, which can be implemented as a fully self‐applicable sleep system. However, cEEGrid signals have different amplitude characteristics to normal scalp PSG signals, which might be challenging for visual scoring. Therefore, this study evaluates the potential of automatic scoring of cEEGrid signals using a machine learning classifier (“random forests”) and compares its performance with manual scoring of standard PSG. In addition, the automatic scoring of cEEGrid signals is compared with manual annotation of the cEEGrid recording and with simultaneous actigraphy. Acceptable recordings were obtained in 15 healthy volunteers (aged 35 ± 14.3 years) during an extended nocturnal sleep opportunity, which induced disrupted sleep with a large inter‐individual variation in sleep parameters. The results demonstrate that machine‐learning‐based scoring of around‐the‐ear EEG outperforms actigraphy with respect to sleep onset and total sleep time assessments. The automated scoring outperforms human scoring of cEEGrid by standard criteria. The accuracy of machine‐learning‐based automated scoring of cEEGrid sleep recordings compared with manual scoring of standard PSG was satisfactory. The findings show that cEEGrid recordings combined with machine‐learning‐based scoring holds promise for large‐scale sleep studies.     

The impact of low-frequency stimulation of subthalamic region on self-generated isometric contraction in patients with Parkinson’s disease

Growing evidence suggests that spontaneous oscillatory low-frequency synchronization in the subthalamic nuclei (STN) may modulate motor performance in patients with Parkinson’s disease (PD). To explore this in more detail, 15 PD patients chronically implanted with deep brain stimulation (DBS) electrodes in both STN were stimulated bilaterally at 5, 10, 20, 50 and 130 Hz and the effects of the DBS on self-initiated isometric elbow flexion (FLEX) and finger pinch (PINCH) were compared to performance without DBS. Baseline performance was very much impaired. Peak force was significantly greater during 130 and 10 Hz stimulation when compared to no stimulation in both tasks. Cumulative sums of the changes in mean rising force and peak force in the two tasks upon stimulation at 10 and 20 Hz demonstrated that patients improved their performance on stimulation, except for those with the best performance off stimulation who deteriorated with stimulation at 20 Hz. Thus, no effect was detected with 20 Hz stimulation at the group level. The current study highlights the need to consider the baseline performance of a subject in a given task when determining the effects of low-frequency STN stimulation in PD patients. It also demonstrates that stimulation at 10 Hz can improve motor function in subjects with poor baseline function.     

Validation of an automated wireless system to monitor sleep in healthy adults

The availability of a reliable system to record sleep stage measures easily and automatically in ambulatory settings could be of utility for research and clinical work. The aim of this study was to evaluate a novel wireless system (WS) that does not require skilled preparation for the automatic collection and scoring of human sleep. Twenty-nine healthy adults underwent concurrent sleep measurement via the WS, polysomnography (PSG) and an actigraph (ACT) in a sleep laboratory for one assessment night preceded by an acclimation night. The PSG recordings were scored by two experienced trained technicians from separate laboratories. Each recording was scored by both technicians to Rechtschaffen and Kales (R&K) criteria. The WS and ACT were compared with each of the PSG scores and a consensus PSG score, and the PSG scores were compared with each other. Inter-rater agreement was assessed for each pair over all pooled epochs by percentage agreement, Cohen's kappa and intraclass correlation coefficient. The WS agreement with each of the two PSG scores for sleep stages was 75.8 and 74.7%, respectively. WS agreement with each of the two PSG scores for sleep/wakefulness was 92.6 and 91.1%, ACT agreement with PSG was 86.3 and 85.7%. The PSG scorers' agreement with each other for sleep stages was 83.2%, and for sleep/wakefulness was 95.8%. The findings from the current study indicate that the WS may provide an easy to use and accurate complement to other established technologies for measuring sleep in healthy adults.     

Wrist actigraphic scoring for sleep laboratory patients: algorithm development

Wrist actigraphy is employed increasingly in sleep research and clinical sleep medicine. Critical evaluation of the performance of new actigraphs and software is needed. Actigraphic sleep–wake estimation was compared with polysomnographic (PSG) scoring as the standard in a clinical sleep laboratory. A convenience sample of 116 patients undergoing clinical sleep recordings volunteered to participate. Actiwatch‐L recordings were obtained from 98 participants, along with 18 recordings using the newer Spectrum model (Philips Electronics), but some of the actigraphic recordings could not be adequately aligned with the simultaneous PSGs. Of satisfactory alignments, 40 Actiwatch recordings were used as a training set to empirically develop a new Scripps Clinic algorithm for sleep–wake scoring. The Scripps Clinic algorithm was then prospectively evaluated in 39 Actiwatch recordings and 16 Spectrum recordings, producing epoch‐by‐epoch sleep–wake agreements of 85–87% and kappa statistics averaging 0.52 (indicating moderate agreement). Wake was underestimated by the scoring algorithm. The correlations of PSG versus actigraphic wake percentage estimates were r = 0.6690 for the Actiwatch and r = 0.2197 for the Spectrum. In general, using a different weighting of activity counts from previous and subsequent epochs, the Scripps Clinic algorithm discriminated sleep–wake more successfully than the manufacturer’s Actiware algorithms. Neither algorithm had fully satisfactory agreement with PSG. Further evaluations of algorithms for these actigraphs are needed, along with controlled comparisons of different actigraphic designs and software.     

Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus

The subthalamic nucleus (STN) is an important component of the basal ganglia (BG) and plays a major role in the pathogenesis of Parkinsons disease (PD). Hyperactivity of STN as a consequence of the loss of dopaminergic inputs to the BG is believed to be a major factor in producing the motor symptoms of PD. High-frequency (HF) deep brain stimulation (DBS) of the STN has recently become an important treatment in PD patients where medications no longer provide satisfactory therapy. However, the mechanisms underlying DBS therapy are unknown, and there is seemingly conflicting data suggesting inhibition or excitation of STN neurons. This study directly examined the effects of stimulation in STN on the activity of STN neurons in PD patients during functional stereotactic mapping prior to insertion of DBS electrodes. Electrical stimulation in STN was investigated in twelve PD patients by recording the neural activity of a cell in STN with one electrode while applying current pulses through a second electrode located about 600 µm away. Stimulation at high frequencies (100–300 Hz) was found to produce inhibition following the stimulus train in 42% of the 60 cells tested. Inhibition during the train was seen in 13 of 15 neurons where it was possible to detect such activity. Furthermore, in 44% of the cases where HF stimulation produced inhibition there was an early inhibition followed by rebound excitation and a further inhibitory period, suggesting that the inhibitions observed are due to hyperpolarization. In eight of the 25 neurons inhibited by HF stimulation, the effects of single stimuli were determined and revealed that in seven of these there was an inhibitory period of 15–20 ms following each stimulus. Thus, the present findings suggest that local HF stimulation inhibits many STN neurons. However, these studies could not determine whether the stimulus also directly excited the cell and/or its axon, but other recent findings suggest that this is likely the case. Therefore, the overall effects of DBS stimulation in STN are likely to be inhibition of intrinsic and synaptically mediated activity, and its replacement by regular high-frequency firing.     

深部脑刺激治疗帕金森病疗效分析

目的研究深部脑刺激（deep brain stimulation，DBS）对帕金森病（Parkinson’s disease，PD）的治疗作用，探讨DBS对PD震颤、肌僵直、运动缓慢的疗效及术中靶点的确定。方法采用微电极记录下丘脑底核（STN）和丘脑腹中间核（Vim）慢性电刺激术对4例PD患者进行治疗。其中3例DBS于STN、1例DBS于Vim。结果3例STN术中刺激发现，能改善PD的震颤、僵直、运动缓慢等主要症状；1例Vim术中刺激发现，患者的震颤和运动缓慢得以改善。4例PD患者经过1～3次的调试，4～6年的随访发现，患者的主要症状改善情况不如短期疗效，但仍较术前有较大改善，通过调节程控参数，可以达到满意。其运动部分（UPDRS）评分，术后改善率43％～48％之间。1例合并上肢疼痛患者经3次调试疼痛症状改善不明显，2年后取出埋藏电极。4例患者均没有出现永久性并发症。结论STN的DBS能改善PD的震颤、僵直、运动缓慢等主要症状；Vim的DBS能改善PD的震颤和运动缓慢。DBS是治疗PD双侧症状的优选方法，其可逆性对患者有较高的安全性。     

Do Patients With Sleep Maintenance Insomnia Have a Problem With Sleep Maintenance?

Do patients with primary insomnia differ from good sleepers with respect to the number or duration of awakenings or to the stages from which awakenings occur? To address this question, polysomnography (PSG) records were evaluated in 10 good sleepers (GS) and 10 primary insomnia patients (PI). PSG records were evaluated for occurrence and duration of awakenings and for the stage immediately preceding each awakening. PIs woke more frequently and for longer durations than did GSs. PIs' awakenings tended to occur from Stages 1 or 2; GSs' occurred from epochs scored as movement times. The data from this study represent the first attempt to characterize the stages from which awakenings occur in sleep maintenance insomnia.     

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.     

Effect of Subthalamic Deep Brain Stimulation on Levodopa-Induced Dyskinesia in Parkinson's Disease

Purpose

To evaluate the effect of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on levodopa-induced peak-dose dyskinesia in patients with Parkinson''s disease (PD).

Materials and Methods

A retrospective review was conducted on patients who underwent STN DBS for PD from May 2000 to July 2012. Only patients with levodopa-induced dyskinesia prior to surgery and more than 1 year of available follow-up data after DBS were included. The outcome measures included the dyskinesia subscore of the Unified Parkinson''s Disease Rating Scale (UPDRS) part IV (items 32 to 34 of UPDRS part IV) and the levodopa equivalent daily dose (LEDD). The patients were divided into two groups based on preoperative to postoperative LEDD change at 12 months after the surgery: Group 1, LEDD decrease >15%; Group 2, all other patients. Group 2 was further divided by the location of DBS leads.

Results

Of the 100 patients enrolled, 67 were in Group 1, while those remaining were in Group 2. Twelve months after STN DBS, Groups 1 and 2 showed improvements of 61.90% and 57.14%, respectively, in the dyskinesia subscore. Group 1 was more likely to experience dyskinesia suppression; however, the association between the groups and dyskinesia suppression was not statistically significant (p=0.619). In Group 2, dyskinesia was significantly decreased by stimulation of the area above the STN in 18 patients compared to stimulation of the STN in 15 patients (p=0.048).

Conclusion

Levodopa-induced dyskinesia is attenuated by STN DBS without reducing the levodopa dosage.     

Pedunculopontine nucleus deep brain stimulation in Parkinson’s disease

Postural instability and gait difficulty (PIGD) are commonly observed in advanced Parkinson’s disease. The neuronal mechanism of PIGD is not fully understood. Dysfunction of the pedunculopontine nucleus (PPN) might be a possible cause of these symptoms. The autopsy studies of subjects with PIGD revealed a neurodegenerative process involving mainly PPN cholinergic neurons. The PPN participates in the locomotion processes by initiation, modulation and execution of stereotyped patterns of movement. The standard neurosurgical treatment of PD is subthalamic deep brain stimulation (STN DBS). Clinical results revealed low efficiency of STN DBS on PIGD. Preliminary results of simultaneous PPN and STN DBS are very promising. Only a few reports have been published until now; a significant improvement of PIGD was observed in both ON and OFF L-dopa states.     

Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization

The local strength of pathological synchronization in the region of the subthalamic nucleus (STN) is emerging as a possible factor in the motor impairment of Parkinson's Disease (PD). In particular, correlations have been repeatedly demonstrated between treatment-induced suppressions of local oscillatory activity in the beta frequency band and improvements in motor performance. However, a mechanistic role for beta activity is brought into question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication. Here we recorded local field potential (LFP) activity from 36 subthalamic regions in 18 patients undergoing functional neurosurgery for the treatment of PD. We recorded directly from the contacts of the deep brain stimulation (DBS) electrodes as they were introduced in successive 2 mm steps, and assessed phase coherence as a measure of spatially extended, rather than local, oscillatory synchronization. We found that phase coherence in the beta frequency band correlated with the severity of Parkinsonian bradykinesia and rigidity, both in the limbs and axial body. Such correlations were frequency and site specific in so far as they were reduced when the lowermost contact of the DBS electrode was above the dorsal STN. Correlations with limb tremor occurred at sub-beta band frequencies and were more lateralized than those between beta activity and limb bradykinesia and rigidity. Phase coherence could account for up to ∼25% of the variance in motor scores between sides and patients. These new data suggest that the strength of spatially extended oscillatory synchronization, as well as the strength of local synchronization, may be worthwhile incorporating into modelling studies designed to inform surgical targeting, post-operative stimulation parameter selection and closed-loop stimulation regimes in PD. In addition, they strengthen the link between pathological synchronization and the different motor features of Parkinsonism.