scholarly journals Neural signatures of pathological hyperdirect pathway activity in Parkinson’s disease

2020 ◽  
Author(s):  
Ashwini Oswal ◽  
Chien-Hung Yeh ◽  
Wolf-Julian Neumann ◽  
James Gratwicke ◽  
Harith Akram ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Computational Modelling ◽  
Spectral Signature ◽  
Fibre Tract ◽  
Cortical Inputs ◽  
High Beta ◽  
Oscillatory Network ◽  
Network Disruption ◽  
Beta Frequency

AbstractParkinson’s disease (PD) is characterised by the emergence of pathological patterns of oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between anatomical connectivity and oscillatory synchronisation within this system remains poorly understood. We address this by integrating evidence from invasive electrophysiology, magnetoencephalography, tractography and computational modelling in patients. Coupling between supplementary motor area (SMA) and subthalamic nucleus (STN) within the high beta frequency (21-30 Hz) range correlated with fibre tract densities between these two structures. Additionally within the STN, non-linear waveform features suggestive of cortical synchronisation correlated with cortico-STN fibre densities. Finally, computational modelling revealed that exaggerated hyperdirect cortical inputs to the STN in the upper beta frequency range can provoke the generation of widespread pathological synchrony at lower beta (13-20 Hz) frequencies. These observations reveal a spectral signature of the hyperdirect pathway at high beta frequencies and provide evidence for its pathophysiological role in oscillatory network dysfunction in PD.One sentence summarySignatures of the hyperdirect pathway and its likely role in pathological network disruption in Parkinson’s disease are identified.

scholarly journals Neural signatures of hyperdirect pathway activity in Parkinson’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashwini Oswal ◽  
Chunyan Cao ◽  
Chien-Hung Yeh ◽  
Wolf-Julian Neumann ◽  
James Gratwicke ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Supplementary Motor Area ◽  
Computational Modelling ◽  
Motor Area ◽  
Internal Globus Pallidus ◽  
Pathway Activity ◽  
High Beta ◽  
Beta Frequency

AbstractParkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21–30 Hz) but not low (13-21 Hz) beta frequency range correlated with ‘hyperdirect pathway’ fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD.

scholarly journals Phase-dependent suppression of beta oscillations in Parkinson’s disease patients

2018 ◽  
Author(s):  
Abbey B. Holt ◽  
Eszter Kormann ◽  
Alessandro Gulberti ◽  
Monika Pötter-Nerger ◽  
Colin G. McNamara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Time Course ◽  
Computational Modelling ◽  
Brain Diseases ◽  
Functional Neurosurgery ◽  
Selective Targeting ◽  
Beta Frequency ◽  
Normal Processing ◽  
Specific Phase

AbstractSynchronized oscillations within and between brain areas facilitate normal processing, but are often amplified in disease. A prominent example is the abnormally sustained beta-frequency (~20Hz) oscillations recorded from the cortex and subthalamic nucleus of Parkinson’s Disease patients. Computational modelling 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 we demonstrate in awake, parkinsonian patients undergoing functional neurosurgery, that electrical stimulation arriving on consecutive cycles of a specific phase of the subthalamic oscillation can suppress its amplitude and coupling to cortex. Stimulus-evoked changes in spiking did not have a consistent time course, suggesting that the oscillation was modulated independently of net output. Phase-dependent stimulation could thus be a valuable strategy for treating brain diseases and probing the function of oscillations in the healthy brain.

scholarly journals Connectivity of EEG synchronization networks increases for Parkinson’s disease patients with freezing of gait

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Eitan E. Asher ◽  
Meir Plotnik ◽  
Moritz Günther ◽  
Shay Moshel ◽  
Orr Levy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Freezing Of Gait ◽  
Motor Task ◽  
Frequency Bands ◽  
Hand Tapping ◽  
Patient Groups ◽  
Beta Frequency ◽  
Relationship Of ◽  
Insight Into

AbstractFreezing of gait (FoG), a paroxysmal gait disturbance commonly experienced by patients with Parkinson’s disease (PD), is characterized by sudden episodes of inability to generate effective forward stepping. Recent studies have shown an increase in beta frequency of local-field potentials in the basal-ganglia during FoG, however, comprehensive research on the synchronization between different brain locations and frequency bands in PD patients is scarce. Here, by developing tools based on network science and non-linear dynamics, we analyze synchronization networks of electroencephalography (EEG) brain waves of three PD patient groups with different FoG severity. We find higher EEG amplitude synchronization (stronger network links) between different brain locations as PD and FoG severity increase. These results are consistent across frequency bands (theta, alpha, beta, gamma) and independent of the specific motor task (walking, still standing, hand tapping) suggesting that an increase in severity of PD and FoG is associated with stronger EEG networks over a broad range of brain frequencies. This observation of a direct relationship of PD/FoG severity with overall EEG synchronization together with our proposed EEG synchronization network approach may be used for evaluating FoG propensity and help to gain further insight into PD and the pathophysiology leading to FoG.

scholarly journals Reversing cognitive–motor impairments in Parkinson’s disease patients using a computational modelling approach to deep brain stimulation programming

Brain ◽  
2010 ◽  
Vol 133 (3) ◽  
pp. 746-761 ◽  
Author(s):  
Anneke M. M. Frankemolle ◽  
Jennifer Wu ◽  
Angela M. Noecker ◽  
Claudia Voelcker-Rehage ◽  
Jason C. Ho ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Computational Modelling ◽  
Motor Impairments ◽  
Deep Brain ◽  
Modelling Approach

scholarly journals Parkinson's disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input in vivo

2020 ◽  
Vol 146 ◽  
pp. 105119
Author(s):  
Magdalena K. Baaske ◽  
Eszter Kormann ◽  
Abbey B. Holt ◽  
Alessandro Gulberti ◽  
Colin G. McNamara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Cortical Input ◽  
Beta Frequency

High beta activity in the subthalamic nucleus and freezing of gait in Parkinson's disease

2014 ◽  
Vol 64 ◽  
pp. 60-65 ◽  
Author(s):  
Jon B. Toledo ◽  
Jon López-Azcárate ◽  
David Garcia-Garcia ◽  
Jorge Guridi ◽  
Miguel Valencia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Freezing Of Gait ◽  
Beta Activity ◽  
High Beta

scholarly journals Parkinson’s disease uncovers an underlying sensitivity of subthalamic nucleus neurons to beta-frequency cortical input

2019 ◽  
Author(s):  
Magdalena K. Baaske ◽  
Eszter Kormann ◽  
Abbey B. Holt ◽  
Alessandro Gulberti ◽  
Colin G. McNamara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subthalamic Nucleus ◽  
Full Range ◽  
Spike Timing ◽  
Cortical Stimulation ◽  
Dopamine Depletion ◽  
Indirect Pathway ◽  
Cortical Input ◽  
Beta Frequency

AbstractAbnormally sustained beta-frequency synchronisation between the motor cortex and subthalamic nucleus (STN) is associated with motor symptoms in Parkinson’s disease (PD). It is currently unclear whether STN neurons have a preference for beta-frequency input (12-35Hz), rather than cortical input at other frequencies, and how such a preference would arise following dopamine depletion. To address this question, we combined analysis of cortical and STN recordings from awake PD patients undergoing deep brain stimulation surgery with recordings of identified STN neurons in anaesthetised rats. In PD patients, we demonstrate that a subset of STN neurons are strongly and selectively sensitive to fluctuations of cortical beta oscillations over time, linearly increasing their phase-locking strength with respect to full range of instantaneous amplitude. In rats, we probed the frequency response of STN neurons more precisely, by recording spikes evoked by short bursts of cortical stimulation with variable frequency (4-40Hz) and constant amplitude. In both healthy and dopamine-depleted animals, only beta-frequency stimulation selectively led to a progressive reduction in the variability of spike timing through the stimulation train. We hypothesize, that abnormal activation of the indirect pathway, via dopamine depletion and/or cortical stimulation, could trigger an underlying sensitivity of the STN microcircuit to beta-frequency input.

scholarly journals Insights into Parkinson’s disease from computational models of the basal ganglia

2018 ◽  
Author(s):  
Mark D. Humphries ◽  
Jose Obeso ◽  
Jakob Kisbye Dreyer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Computational Models ◽  
Neural Circuits ◽  
Computational Modelling ◽  
Beta Band ◽  
Complex Interplay ◽  
Deep Brain

AbstractMovement disorders arise from the complex interplay of multiple changes to neural circuits. Successful treatments for these disorders could interact with these complex changes in myriad ways, and as a consequence their mechanisms of action and their amelioration of symptoms are incompletely understood. Using Parkinson’s disease as a case-study, we review here how computational models are a crucial tool for taming this complexity, across causative mechanisms, consequent neural dynamics, and treatments. For mechanisms, we review models that capture the effects of losing dopamine on basal ganglia function; for dynamics, we discuss models that have transformed our understanding of how beta-band (15-30 Hz) oscillations arise in the parkinsonian basal ganglia. For treatments, we touch on the breadth of computational modelling work trying to understand the therapeutic actions of deep brain stimulation. Collectively, models from across all levels of description are providing a compelling account of the causes, symptoms, and treatments for Parkinson’s disease.

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