Dopamine and beta-band oscillations differentially link to striatal value and motor control

Parkinson’s disease is characterized by decreased dopamine and increased beta-band oscillatory activity accompanying debilitating motor and mood impairments. Coordinate dopamine-beta opposition is considered a normative rule for basal ganglia function. We report a breakdown of this rule. We developed multimodal systems allowing the first simultaneous, chronic recordings of dopamine release and beta-band activity in the striatum of nonhuman primates during behavioral performance. Dopamine and beta signals were anticorrelated over seconds-long time frames, in agreement with the posited rule, but at finer time scales, we identified conditions in which these signals were modulated with the same polarity. These measurements demonstrated that task-elicited beta suppressions preceded dopamine peaks and that relative dopamine-beta timing and polarity depended on reward value, performance history, movement, and striatal domain. These findings establish a new view of coordinate dopamine and beta signaling operations, critical to guide novel strategies for diagnosing and treating Parkinson’s disease and related neurodegenerative disorders.

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Parkinson's disease and pathological oscillatory activity: Is the beta band the bad guy? — New lessons learned from low-frequency deep brain stimulation

Experimental Neurology ◽

10.1016/j.expneurol.2011.10.022 ◽

2012 ◽

Vol 233 (1) ◽

pp. 123-125 ◽

Cited By ~ 14

Author(s):

Lars Timmermann ◽

Esther Florin

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Low Frequency ◽

Lessons Learned ◽

Oscillatory Activity ◽

Beta Band ◽

Deep Brain

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Increase in Beta-Band Activity during Preparation for Overt Speech in Patients with Parkinson’s Disease

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2017.00371 ◽

2017 ◽

Vol 11 ◽

Cited By ~ 1

Author(s):

Peter Sörös ◽

Nuria Doñamayor ◽

Catharina Wittke ◽

Mohamed Al-Khaled ◽

Norbert Brüggemann ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Beta Band ◽

Overt Speech ◽

Band Activity

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Bilateral symmetry and coherence of subthalamic nuclei beta band activity in Parkinson's disease

Experimental Neurology ◽

10.1016/j.expneurol.2009.11.012 ◽

2010 ◽

Vol 221 (1) ◽

pp. 260-266 ◽

Cited By ~ 59

Author(s):

Camille de Solages ◽

Bruce C. Hill ◽

Mandy Miller Koop ◽

Jaimie M. Henderson ◽

Helen Bronte-Stewart

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Bilateral Symmetry ◽

Beta Band ◽

Band Activity

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Reduction of spontaneous cortical beta bursts in Parkinson’s disease is linked to symptom severity

10.1101/775494 ◽

2019 ◽

Author(s):

Mikkel C. Vinding ◽

Panagiota Tsitsi ◽

Josefine Waldthaler ◽

Robert Oostenveld ◽

Martin Ingvar ◽

...

Keyword(s):

Parkinson’S Disease ◽

Time Series ◽

Parkinson's Disease ◽

Symptom Severity ◽

Time Course ◽

High Amplitude ◽

Motor Symptom ◽

Healthy Controls ◽

Beta Band ◽

Band Activity

AbstractParkinson’s disease is characterized by a gradual loss of dopaminergic neurons, which are associated with altered neuronal activity in the beta band (13-30 Hz). Assessing beta band activity typically involves transforming the time-series to get the power of the signal in the frequency-domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine-and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta band activity—for example, that the beta band exhibits transient bursts of high-amplitude activity.In an exploratory study we used magnetoencephalography (MEG) to record cortical beta band activity to characterize how spontaneous cortical beta bursts manifest in Parkinson’s patients ON and OFF dopaminergic medication, and compare this to matched healthy controls. From three minutes of MEG data, we extracted the time-course of beta band activity from the sensorimotor cortex and characterized high-amplitude epochs in the signal to test if they exhibited burst like properties. We then compared the rate, duration, inter-burst interval, and peak amplitude of the high-amplitude epochs between the Parkinson’s patients and healthy controls.Our results show that Parkinson’s patients OFF medication had a 6-17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for Parkinson’s patients and healthy controls and medicated state of the Parkinson’s patients. These data thus support the view that beta bursts are fundamental underlying features of beta band activity, and show that changes in cortical beta band power in PD can be explained primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta bursts rate and motor symptom severity in PD: a lower burst rate scaled with increased in severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as neuromarker for Parkinson’s disease that can help in the assessment of symptom severity in Parkinson’s disease or evaluate treatment effectiveness.

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Attenuated beta rebound to proprioceptive afferent feedback in Parkinson’s disease

10.1101/334565 ◽

2018 ◽

Author(s):

Mikkel C. Vinding ◽

Panagiota Tsitsi ◽

Harri Piitulainen ◽

Josefine Waldthaler ◽

Veikko Jousmäki ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Passive Movement ◽

Afferent Feedback ◽

Oscillatory Activity ◽

Cortical Processing ◽

Beta Band ◽

Proprioceptive Stimulation ◽

Proprioceptive Function

AbstractMotor symptoms are defining traits in the diagnosis of Parkinson’s disease (PD). A crucial component in motor function and control of movements is the integration of efferent signals from the motor network to the peripheral motor system, and afferent proprioceptive sensory feedback. Previous studies have indicated abnormal movement-related cortical oscillatory activity in PD, but the role of the proprioceptive afference on abnormal oscillatory activity in PD has not been elucidated. In the present study, we examine the role of proprioception by studying the cortical processing of proprioceptive stimulation in PD patients, ON/OFF levodopa medication, as compared to that of healthy controls (HC). We used a proprioceptive stimulator that generated precisely controlled passive movements of the index finger and measured the induced cortical oscillatory responses following the proprioceptive stimulation using magnetoencephalography (MEG). Both PD patients and HC showed a typical initial mu/beta-band (8–30 Hz) desynchronization during the passive movement. However, the subsequent beta rebound after the passive movement that was apparent in HC was much attenuated and almost absent in PD patients. Furthermore, we found no difference in the degree of beta rebound attenuation between patients ON and OFF levodopa medication. Our results hence demonstrate a disease-related deterioration in cortical processing of proprioceptive afference in PD, and further suggest that such disease-related loss of proprioceptive function is due to processes outside the dopaminergic system affected by levodopa medication.

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Autonomous oscillations and phase-locking in a biophysically detailed model of the STN-GPe network

10.1101/611103 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lucas A. Koelman ◽

Madeleine M. Lowery

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Oscillation Frequency ◽

Phase Locking ◽

Oscillatory Activity ◽

Relative Role ◽

Beta Band ◽

Detailed Model ◽

Dendritic Structures ◽

Phase Relationships

AbstractThe aim of this study was to understand the relative role of autonomous oscillations and patterning by exogenous oscillatory inputs in the generation of pathological oscillatory activity within the subthalamic nucleus (STN) - external globus pallidus (GPe) network in Parkinson’s disease. A biophysically detailed model that accounts for the integration of synaptic currents and their interaction with intrinsic membrane currents in dendritic structures within the STN and GPe was developed. The model was used to investigate the development of beta-band synchrony and bursting within the STN-GPe network by changing the balance of excitation and inhibition in both nuclei, and by adding exogenous oscillatory inputs with varying phase relationships through the hyperdirect cortico-subthalamic and indirect striato-pallidal pathways. The model showed an intrinsic susceptibility to beta-band oscillations that was manifest in weak autonomously generated oscillations within the STN-GPe network and in selective amplification of exogenous beta-band synaptic inputs near the network’s endogenous oscillation frequency. The resonant oscillation frequency was determined by the net level of excitatory drive in the loop. Intrinsically generated oscillations were too weak to support a pacemaker role for the STN-GPe network, however, they were considerably amplified by sparse cortical beta inputs when their frequency range overlapped and were further amplified by striatal beta inputs that promoted anti-phase firing of the cortex and GPe, resulting in maximum transient inhibition of STN neurons. The model elucidates a mechanism of cortical patterning of the STN-GPe network through feedback inhibition whereby intrinsic susceptibility to beta-band oscillations can lead to phase locked spiking under parkinsonian conditions. These results point to resonance of endogenous oscillations with exogenous patterning of the STN-GPe network as a mechanism of pathological synchronization, and a role for the pallido-striatal feedback loop in amplifying beta oscillations.Author summaryExaggerated beta-frequency neuronal synchrony is observed throughout the basal ganglia in Parkinson’s disease and is reduced with medication and during deep brain stimulation. The power of beta-band oscillations is increasingly used as a biomarker to guide antiparkinsonian therapies. Despite their importance as a clinical target, the mechanisms by which pathological beta-band oscillations are generated are not yet clearly understood. In vitro electrophysiological recordings support a theory of enhanced phase locking of the reciprocally connected subthalamo-pallidal network to beta-band cortical inputs but this has not yet been clearly demonstrated in a model. We present a new model of the subthalamo-pallidal network consisting of biophysically detailed cell models that captures the interaction between synaptic and intrinsic currents in dendritic structures. The model shows how phase locking of subthalamic and pallidal neurons and exaggerated bursting in subthalamic neurons can arise from the interaction of these currents when the balance of excitation and inhibition is changed and how phase locking is amplified under specific phase relationships between cortical and striatal beta inputs.

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Bursts of beta oscillation differentiate postperformance activity in the striatum and motor cortex of monkeys performing movement tasks

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1517629112 ◽

2015 ◽

Vol 112 (44) ◽

pp. 13687-13692 ◽

Cited By ~ 151

Author(s):

Joseph Feingold ◽

Daniel J. Gibson ◽

Brian DePasquale ◽

Ann M. Graybiel

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Cortex ◽

Time Scale ◽

Premotor Cortex ◽

Short Time Scale ◽

Beta Activity ◽

Beta Band ◽

Time Specific ◽

Band Activity

Studies of neural oscillations in the beta band (13–30 Hz) have demonstrated modulations in beta-band power associated with sensory and motor events on time scales of 1 s or more, and have shown that these are exaggerated in Parkinson’s disease. However, even early reports of beta activity noted extremely fleeting episodes of beta-band oscillation lasting <150 ms. Because the interpretation of possible functions for beta-band oscillations depends strongly on the time scale over which they occur, and because of these oscillations’ potential importance in Parkinson’s disease and related disorders, we analyzed in detail the distributions of duration and power for beta-band activity in a large dataset recorded in the striatum and motor-premotor cortex of macaque monkeys performing reaching tasks. Both regions exhibited typical beta-band suppression during movement and postmovement rebounds of up to 3 s as viewed in data averaged across trials, but single-trial analysis showed that most beta oscillations occurred in brief bursts, commonly 90–115 ms long. In the motor cortex, the burst probabilities peaked following the last movement, but in the striatum, the burst probabilities peaked at task end, after reward, and continued through the postperformance period. Thus, what appear to be extended periods of postperformance beta-band synchronization reflect primarily the modulated densities of short bursts of synchrony occurring in region-specific and task-time-specific patterns. We suggest that these short-time-scale events likely underlie the functions of most beta-band activity, so that prolongation of these beta episodes, as observed in Parkinson’s disease, could produce deleterious network-level signaling.

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Reduction of spontaneous cortical beta bursts in Parkinson’s disease is linked to symptom severity

Brain Communications ◽

10.1093/braincomms/fcaa052 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Mikkel C Vinding ◽

Panagiota Tsitsi ◽

Josefine Waldthaler ◽

Robert Oostenveld ◽

Martin Ingvar ◽

...

Keyword(s):

Parkinson’S Disease ◽

Time Series ◽

Parkinson's Disease ◽

Sensorimotor Cortex ◽

Symptom Severity ◽

Time Course ◽

Motor Symptom ◽

Healthy Controls ◽

Beta Band ◽

Band Activity

Abstract Parkinson’s disease is characterized by a gradual loss of dopaminergic neurons, which is associated with altered neuronal activity in the beta-band (13–30 Hz). Assessing beta-band activity typically involves transforming the time-series to get the power of the signal in the frequency domain. Such transformation assumes that the time-series can be reduced to a combination of steady-state sine- and cosine waves. However, recent studies have suggested that this approach masks relevant biophysical features in the beta-band—for example, that the beta-band exhibits transient bursts of high-amplitude activity. In an exploratory study, we used magnetoencephalography to record beta-band activity from the sensorimotor cortex, to characterize how spontaneous cortical beta bursts manifest in Parkinson’s patients on and off dopaminergic medication, and compare this to matched healthy controls. We extracted the time-course of beta-band activity from the sensorimotor cortex and characterized bursts in the signal. We then compared the burst rate, duration, inter-burst interval and peak amplitude between the Parkinson’s patients and healthy controls. Our results show that Parkinson’s patients off medication had a 5–17% lower beta bursts rate compared to healthy controls, while both the duration and the amplitude of the bursts were the same for healthy controls and medicated state of the Parkinson’s patients. These data thus support the view that beta bursts are fundamental underlying features of beta-band activity, and show that changes in cortical beta-band power in Parkinson’s disease can be explained—primarily by changes in the underlying burst rate. Importantly, our results also revealed a relationship between beta burst rate and motor symptom severity in Parkinson’s disease: a lower burst rate scaled with increased severity of bradykinesia and postural/kinetic tremor. Beta burst rate might thus serve as a neuromarker for Parkinson’s disease that can help in the assessment of symptom severity in Parkinson’s disease or in the evaluation of treatment effectiveness.

Download Full-text