Premotor cortical beta synchronization and the network neuromodulation of externally paced finger tapping in Parkinson's disease.

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.

Therapeutic use of medical Cannabis in neurological diseases: a clinical update.

The use of medical Cannabis has increased in recent years due to changing legal circumstances in many countries. Approval exists only for a few neurological conditions such as rare forms of epilepsy or spasticity in multiple sclerosis. Beyond that, however, medical Cannabis is used for a wide range of neurological conditions and symptoms. In Germany, in parallel with new legislation that has simplified the prescription of medical Cannabis, an accompanying survey has been implemented for which initial data are now available. In this context, our review provides an overview of the evidence for the therapeutic use of medical Cannabis in neurology, the potential benefits, and side effects.

Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.

BACKGROUND: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). OBJECTIVES: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. METHODS: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. RESULTS: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). CONCLUSIONS: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Automatic covariance pattern analysis outperforms visual reading of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in variant progressive supranuclear palsy.

BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Blood neurofilament light chain in Parkinson's disease.

Blood neurofilament light chain (NfL) is an easily accessible, highly sensitive and reliable biomarker for neuroaxonal damage. Currently, its role in Parkinson's disease (PD) remains unclear. Here, we demonstrate that blood NfL can distinguish idiopathic PD from atypical parkinsonian syndromes (APS) with high sensitivity and specificity. In cross-sectional studies, some found significant correlations between blood NfL with motor and cognitive function, whereas others did not. In contrast, prospective studies reported very consistent associations between baseline blood NfL with motor progression and cognitive worsening. Amongst PD subtypes, especially postural instability and gait disorder (PIGD) subtype, symptoms and scores are reliably linked with blood NfL. Different non-motor PD comorbidities have also been associated with high blood NfL levels suggesting that the neuroaxonal damage of the autonomic nervous system as well as serotonergic, cholinergic and noradrenergic neurons is quantifiable. Numerous absolute NfL cutoff levels have been suggested in different cohort studies; however, validation across cohorts remains weak. However, age-adjusted percentiles and intra-individual blood NfL changes might represent more valid and consistent parameters compared with absolute NfL concentrations. In summary, blood NfL has the potential as biomarker in PD patients to be used in clinical practice for prediction of disease severity and especially progression.

Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor.

OBJECTIVE: Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. MATERIALS AND METHODS: We recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 µs and 30 µs. RESULTS: All stimulation conditions reduced tremor. The best directional stimulation with 60 µs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 µs attenuated paresthesia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. The best directional stimulation with 30 µs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 µs than with conventional 60 µs stimulation. CONCLUSION: Directional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.

Diabetes, Glycated Hemoglobin (HbA1c), and Neuroaxonal Damage in Parkinson's Disease (MARK-PD Study).

BACKGROUND: Diabetes is associated with incidence and prevalence of Parkinson's disease (PD). Furthermore, glycated hemoglobin (HbA1c) levels have been linked with motor function and progression. OBJECTIVES: We evaluated the relationship between prevalent diabetes and HbA1c levels with serum neurofilament light chain (NfL) levels as marker of neuroaxonal damage. METHODS: NfL concentrations were analyzed with Simoa in serum of 195 PD patients with available HbA1c values. Motor (MDS-UPDRS III, Hoehn & Yahr [H&Y]) and cognitive (Montreal Cognitive Assessment [MoCA]) function was assessed and vascular comorbidities were documented from medical records. RESULTS: PD patients with prevalent diabetes had higher serum NfL levels and lower MoCA scores independent of age, body mass index (BMI), and vascular risk factors. Furthermore, diabetes was associated with higher H&Y stages in unadjusted and age/BMI-adjusted models. Higher HbA1c levels were associated with increased NfL in unadjusted and age/BMI-adjusted models. CONCLUSIONS: In PD patients, diabetes and high HbA1c are associated with increased neuroaxonal damage and cognitive impairment. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Blood-based biomarker in Parkinson's disease: potential for future applications in clinical research and practice.

The clinical presentation of Parkinson's disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher's and a clinician's perspective on recent developments and potential future applications.

Serum neurofilament light chain and postural instability/gait difficulty (PIGD) subtypes of Parkinson's disease in the MARK-PD study.

The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson's Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.

[Relevance of COMT inhibitors in the treatment of motor fluctuations]. / Stellenwert der COMT-Hemmer in der Therapie motorischer Fluktuationen.

Catechol O­methyltransferase (COMT) inhibitors have been established in the treatment of Parkinson's disease for more than 20 years. They are considered the medication of choice for treating motor fluctuations. The available COMT inhibitors, entacapone, opicapone and tolcapone, differ pharmacokinetically in terms of their half-lives with implications for the dose frequency, in their indication requirements and in their spectrum of side effects, including diarrhea and yellow discoloration of urine. Many patients with motor fluctuations are currently not treated with COMT inhibitors and are, therefore, unlikely to receive individually optimized drug treatment. This manuscript summarizes the results of a working group including several Parkinson's disease experts, in which the value of COMT inhibitors was critically discussed.

[Treatment of Sialorrhea with Botulinum Neurotoxin Type A - Consensus Practice Recommendations for Children and Adults]. / Behandlung der Sialorrhoe mit Botulinum Neurotoxin Typ A ­ Konsentierte Praxisempfehlungen für Kinder und Erwachsene.

Sialorrhea, uncontrolled, excessive drooling, accompanies different, mostly neurological disorders from childhood to adulthood. With incobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH), an approved medication for the treatment of sialorrhea has been available since 2019. Patient selection, possible therapy goals, treatment and the management of specific treatment situations build the focus of this interdisciplinary expert consensus recommendations with the intent to facilitate access to treatment and to contribute to qualified botulinum toxin therapy.

The ability of the eating assessment tool-10 to detect penetration and aspiration in Parkinson's disease.

PURPOSE: Dysphagia is common in patients with Parkinson's disease (PD) and often leads to pneumonia, malnutrition, and reduced quality of life. This study investigates the ability of the Eating Assessment Tool-10 (EAT-10), an established, easy self-administered screening tool, to detect aspiration in PD patients. This study aims to validate the ability of the EAT-10 to detect FEES-proven aspiration in patients with PD. METHODS: In a controlled prospective cross-sectional study, a total of 50 PD patients completed the EAT-10 and, subsequently, were examined by Flexible Endoscopic Evaluation of Swallowing (FEES) to determine the swallowing status. The results were rated through the Penetration-Aspiration Scale (PAS) and data were analyzed retrospectively. RESULTS: PAS and EAT-10 did not correlate significantly. Selected items of the EAT-10 could not predict aspiration or residues. 19 (38%) out of 50 patients with either penetration or aspiration were not detected by the EAT-10. The diagnostic accuracy was established at only a sufficient level (AUC 0.65). An optimal cut-off value of ≥ 6 presented a sensitivity of 58% and specificity of 82%. CONCLUSIONS: The EAT-10 is not suited for the detection of penetration and aspiration in PD patients. Therefore, it cannot be used as a screening method in this patient population. There is still a need for a valid, simple, and efficient screening tool to assist physicians in their daily diagnostics and to avoid clinical complications.

Phase-Dependent Suppression of Beta Oscillations in Parkinson's Disease Patients.

Synchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (∼20 Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson's disease patients. Computational modeling suggests that the amplitude of such oscillations could be modulated by applying stimulation at a specific phase. Such a strategy would allow selective targeting of the oscillation, with relatively little effect on other activity parameters. Here, activity was recorded from 10 awake, parkinsonian patients (6 male, 4 female human subjects) undergoing functional neurosurgery. We demonstrate that stimulation arriving on a particular patient-specific phase of the beta oscillation over consecutive cycles could suppress the amplitude of this pathophysiological activity by up to 40%, while amplification effects were relatively weak. Suppressive effects were accompanied by a reduction in the rhythmic output of subthalamic nucleus (STN) neurons and synchronization with the mesial cortex. While stimulation could alter the spiking pattern of STN neurons, there was no net effect on firing rate, suggesting that reduced beta synchrony was a result of alterations to the relative timing of spiking activity, rather than an overall change in excitability. Together, these results identify a novel intrinsic property of cortico-basal ganglia synchrony that suggests the phase of ongoing neural oscillations could be a viable and effective control signal for the treatment of Parkinson's disease. This work has potential implications for other brain diseases with exaggerated neuronal synchronization and for probing the function of rhythmic activity in the healthy brain.SIGNIFICANCE STATEMENT In Parkinson's disease (PD), movement impairment is correlated with exaggerated beta frequency oscillations in the cerebral cortex and subthalamic nucleus (STN). Using a novel method of stimulation in PD patients undergoing neurosurgery, we demonstrate that STN beta oscillations can be suppressed when consecutive electrical pulses arrive at a specific phase of the oscillation. This effect is likely because of interrupting the timing of neuronal activity rather than excitability, as stimulation altered the firing pattern of STN spiking without changing overall rate. These findings show the potential of oscillation phase as an input for "closed-loop" stimulation, which could provide a valuable neuromodulation strategy for the treatment of brain disorders and for elucidating the role of neuronal oscillations in the healthy brain.

A New Stimulation Mode for Deep Brain Stimulation in Parkinson's Disease: Theta Burst Stimulation.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess efficacy and safety of a new patterned theta burst stimulation algorithm of DBS with the aim of expanding the therapeutic window and clinical benefit in PD. METHODS: In this single-center, randomized, double-blind, clinical short-term trial, unilateral conventional subthalamic DBS was compared with unilateral patterned stimulation algorithms with intraburst high- or low-frequency theta burst stimulation in 17 PD patients. RESULTS: There were no serious adverse events with theta burst stimulation. During monopolar review, conventional subthalamic DBS and high-frequency theta burst stimulation were comparable, but low-frequency theta burst stimulation differed by requiring higher stimulation amplitudes for symptom reduction, but a larger therapeutic window. High- and low-frequency theta burst stimulation with adapted stimulation amplitude were effective in PD symptom reduction with differential effects on akinesia and tremor, depending on the theta burst stimulation mode. CONCLUSIONS: Theta burst stimulation is a safe and effective stimulation mode with potential future application opportunities. © 2020 International Parkinson and Movement Disorder Society.

Subclinical Cardiac Microdamage, Motor Severity, and Cognition in Parkinson's Disease.

BACKGROUND: We assessed if cardiac blood markers are associated with motor and cognitive function in patients with Parkinson's disease (PD). METHODS: High-sensitivity troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were evaluated in 285 PD patients. Furthermore, N-terminal pro-B-type natriuretic peptide levels were analyzed in 570 age, sex and cardiovascular risk factor matched healthy controls. Motor (UPDRS, Hoehn &Yahr) and cognitive function (Montreal Cognitive Assessemtn) were assessed at baseline in all 285 patients and after 1 year in 101 patients. RESULTS: N-terminal pro-B-type natriuretic peptide were significantly increased in 285 PD patients compared with 570 matched healthy controls. In PD patients, increased high-sensitivity troponin I and N-terminal pro-B-type natriuretic peptide levels were associated with worse motor function at baseline and also with motor decline after 1 year. N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I were inversely associated with cognitive function at baseline only in unadjusted models. CONCLUSIONS: Subclinical cardiac microdamage is associated with motor severity in PD patients. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dopamine boosts intention and action awareness in Parkinson's disease.

Dopaminergic deficiency in Parkinson's disease (PD) has been associated with underactivation of the supplementary motor area and a reduction of voluntary actions. In these patients, awareness of intention to act has been shown to be delayed. However, delayed awareness of intention to act has also been shown in patients with hyperdopaminergic states and an excess of unwilled movements, as in Tourette's, and in patients with functional movement disorders. Hence, the role of dopamine in the awareness of intention and action remains unclear. 36 PD patients were tested ON and OFF dopaminergic medication and compared with 35 healthy age-matched controls. In addition, 17 PD patients with subthalamic deep brain stimulation (DBS) were tested ON medication and ON and OFF stimulation. Participants judged either the moment a self-generated action was performed, or the moment the urge to perform the action was felt, using the "Libet method". Temporal judgments of intention and action awareness were comparable between unmedicated PD patients and controls. Dopaminergic medication boosted anticipatory awareness of both intentions and actions in PD patients, relative to an unmedicated condition. The difference between ON/OFF DBS was not statistically reliable. Functional improvement of motor ability in PD through dopaminergic supplementation leads to earlier awareness of both intention, and of voluntary action.

[Recommendation for the differentiated use of nuclear medical diagnostic for parkinsonian syndromes]. / Empfehlung zum differenzierten Einsatz nuklearmedizinischer Diagnostik bei Parkinson-Syndromen.

The present work provides an overview of the various nuclear medicine methods in the diagnosis of neurodegenerative parkinsonian syndromes and their respective evidence and is intended to enable practical decision-making aids in the application and interpretation of the methods and findings. The value of the procedures differs considerably in relation to the two relevant diagnostic questions. On the one hand, it is the question of whether there is a neurodegenerative parkinsonian syndrome at all, and on the other hand the question of which one. While the DAT-SPECT is undisputedly the method of choice for answering the first question (taking certain parameters into account), this method is not suitable for answering the second question. To categorise parkinsonian syndromes into idiopathic (i. e. Parkinson´s disease) or atypical, various procedures are used in everyday clinical practice including MIBG scintigraphy, and FDG-PET. We explain why FDG-PET currently is not only the most suitable of these methods to differentiate an idiopathic parkinsonian syndrome, from an atypical Parkinson's syndrome, but also enables sufficiently valid to distinguish the various atypical neurodegenerative Parkinson's syndromes (i. e. MSA, PSP and CBD) from each other and therefore should be reimbursed by health insurances.

Evidence for the use of cannabinoids in Parkinson's disease.

Cannabis and synthetic cannabinoid formulations have now been legally approved in several countries for treatment of patients with Parkinson's disease (PD). Hence, PD patients consult physicians more frequently for prescription of cannabinoids to alleviate symptoms that might not respond well to dopaminergic treatment. Despite the increasing volume of research generated in the field of cannabinoids and their effect on Parkinson's disease, there is still paucity of sufficient clinical data about the efficacy and safety in PD patients. There is increasing understanding of the endocannabinoid system, and the distribution of cannabinoid receptors in basal ganglia structures might suggest potential benefit on parkinsonian symptoms. Concerning clinical research, only one of to date four conducted randomized placebo-controlled trials showed an effect on motor symptoms with alleviation of levodopa-induced dyskinesia. There are a growing number of uncontrolled trials and case reports that suggest beneficial effects of cannabinoids in PD patients. However, the variety of substances investigated, the varying routes of intake, differing doses and time courses make it difficult to compare data. We here provide an overview of the current literature in this field and discuss a pragmatic approach for the clinical use of cannabinoids in PD.

Dyskinesia in multiple system atrophy and progressive supranuclear palsy.

In the differential diagnosis of Parkinson syndromes, the response to L-Dopa is an essential criterion for the diagnosis of idiopathic Parkinson's syndrome (IPS), and the presence of L-Dopa-induced dyskinesia (LID) is considered a supportive criterion. This implies that in the presence of LID an atypical Parkinson-syndrome (APS) is unlikely. However, dyskinesia, and in particular LID, can also be present in APS such as MSA and PSP, although less frequently, and with varying clinical appearance. We conclude that whilst presence of dyskinesia provides support for a diagnosis of IPD, they do not allow reliable differentiation from APS.

Spatio-temporal dynamics of cortical drive to human subthalamic nucleus neurons in Parkinson's disease.

Pathological synchronisation of beta frequency (12-35Hz) oscillations between the subthalamic nucleus (STN) and cerebral cortex is thought to contribute to motor impairment in Parkinson's disease (PD). For this cortico-subthalamic oscillatory drive to be mechanistically important, it must influence the firing of STN neurons and, consequently, their downstream targets. Here, we examined the dynamics of synchronisation between STN LFPs and units with multiple cortical areas, measured using frontal ECoG, midline EEG and lateral EEG, during rest and movement. STN neurons lagged cortical signals recorded over midline (over premotor cortices) and frontal (over prefrontal cortices) with stable time delays, consistent with strong corticosubthalamic drive, and many neurons maintained these dynamics during movement. In contrast, most STN neurons desynchronised from lateral EEG signals (over primary motor cortices) during movement and those that did not had altered phase relations to the cortical signals. The strength of synchronisation between STN units and midline EEG in the high beta range (25-35Hz) correlated positively with the severity of akinetic-rigid motor symptoms across patients. Together, these results suggest that sustained synchronisation of STN neurons to premotor-cortical beta oscillations play an important role in disrupting the normal coding of movement in PD.