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

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.

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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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Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity

PLoS ONE ◽

10.1371/journal.pone.0065352 ◽

2013 ◽

Vol 8 (6) ◽

pp. e65352 ◽

Cited By ~ 13

Author(s):

Antonio Ciaramella ◽

Francesca Salani ◽

Federica Bizzoni ◽

Francesco E. Pontieri ◽

Alessandro Stefani ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dendritic Cell ◽

Symptom Severity ◽

Motor Symptom ◽

Idiopathic Parkinson’S Disease ◽

Cell Frequency ◽

Idiopathic Parkinson's Disease ◽

Blood Dendritic Cell

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Cross-frequency phase-amplitude coupling in repetitive movements in patients with Parkinson's disease

10.1101/2021.07.26.21261085 ◽

2021 ◽

Author(s):

Ruxue Gong ◽

Christoph Mühlberg ◽

Mirko Wegscheider ◽

Christopher Fricke ◽

Jost-Julian Rumpf ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Primary Motor Cortex ◽

Premotor Cortex ◽

Neuronal Population ◽

Motor Symptom ◽

Healthy Controls ◽

Eeg Signals ◽

Oscillatory Eeg ◽

Phase Amplitude

Bradykinesia is a cardinal motor symptom in Parkinson's disease whose pathophysiology is incompletely understood. When signals are recorded from the cortex or scalp at rest, affected patients display enhanced phase-amplitude coupling between β (13-30Hz) and broadband γ (50-150Hz) oscillatory activities. However, it remains unclear whether and how abnormal phase-amplitude coupling is involved in slowing Parkinsonian movements during their execution. To address these questions, we analyzed high-density EEG signals recorded simultaneously with various motor activities and at rest in 19 patients with Parkinson's disease and 20 healthy controls. The motor tasks consisted of repetitive index finger pressing, and slow and fast tapping movements. Individual EEG source signals were computed for the premotor cortex, primary motor cortex, primary somatosensory cortex, and primary somatosensory complex. For the resting condition and the pressing task, phase-amplitude coupling averaged over the 4 motor regions and the entire movement period was larger in patients than in controls. In contrast, in all tapping tasks, state-related phase-amplitude coupling was similar between patients and controls. These findings were not aligned with motor performance and EMG data, which showed abnormalities in patients for tapping but not for pressing, suggesting that the strength of β-broadband γ phase-amplitude coupling during the movement period does not directly relate to Parkinsonian bradykinesia. Subsequently, we examined the dynamics of oscillatory EEG signals during motor transitions. When healthy controls performed the pressing task, dynamic phase-amplitude coupling increased shortly before pressing onset and decreased subsequently. A strikingly similar motif of coupling rise and decay was observed around the offset of pressing and around the onset of slow tapping, suggesting that such transient phase-amplitude coupling changes may be linked to transitions between different movement states - akin to preparatory states in dynamical systems theory of motor control. In patients, the modulation of phase-amplitude coupling was similar in (normally executed) pressing, but flattened in slow (abnormally executed) tapping compared to the controls. These deviations in phase-amplitude coupling around motor action transients may indicate dysfunctional evolution of neuronal population dynamics from the preparatory state to movement generation in Parkinson's disease. These findings may indicate that cross-frequency coupling is involved in the pathophysiology of bradykinesia in Parkinson's disease through its abnormal dynamic modulation.

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A-089 The Role of Anxiety Severity and Neurocognitive Functions in Parkinson’s Disease

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acaa068.089 ◽

2020 ◽

Vol 35 (6) ◽

pp. 882-882

Author(s):

Lee G ◽

Suhr J ◽

Boxley L ◽

Nguyen C

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Severity ◽

Neurodegenerative Disorder ◽

Analysis Of Covariance ◽

Motor Symptom ◽

Group Differences ◽

Significant Group ◽

Neurocognitive Functions

Abstract Objective Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. While much of the extant literature on neuropsychiatric symptoms and cognitive deficits have focused on depression, comparatively less have examined the role of anxiety among patients with PD. Here, we examined levels of anxiety severity (i.e., minimal, mild, moderate–severe) and cognition in this population. Method Fifty-six PD patients (M age = 60.8 ± 9.3; 69.6% male) being considered for surgical intervention were evaluated at an outpatient clinic. Inclusion criteria included no history of neurosurgical procedure and no other diagnosis of a neurodegenerative disorder. Participants completed a battery of neuropsychological tests and reported mood symptoms (Geriatric Depression Scale-15, Beck Anxiety Inventory). Those who scored above clinical cutoffs for depressive symptoms were excluded due to high comorbidity with anxiety. Motor symptom severity was rated by neurologists using the Unified Parkinson’s Disease Rating Scale. Results Analysis of covariance revealed significant group differences on tests of working memory (p = .03), set-shifting (p = .04), problem-solving (p = .05), and phonemic fluency (p = .03) when controlling for motor symptom severity. PD patients with moderate–severe levels of anxiety performed significantly lower than those with minimal or mild anxiety (p’s < .05). There were no other significant group differences in neuropsychological test performance. Conclusions These findings suggest measurable differences in neurocognitive functions associated with frontostriatal circuits among PD patients with varying levels of overall anxiety. Future work should consider the potential overlap between anxiety and PD symptoms as they relate to cognition.

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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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Linguistic correlates of asymmetric motor symptom severity in Parkinson’s Disease

Brain and Cognition ◽

10.1016/j.bandc.2009.08.004 ◽

2010 ◽

Vol 72 (2) ◽

pp. 189-196 ◽

Cited By ~ 15

Author(s):

Thomas Holtgraves ◽

Patrick McNamara ◽

Kevin Cappaert ◽

Raymond Durso

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Severity ◽

Motor Symptom

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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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Computational medication regimen for Parkinson’s disease using reinforcement learning

Scientific Reports ◽

10.1038/s41598-021-88619-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yejin Kim ◽

Jessika Suescun ◽

Mya C. Schiess ◽

Xiaoqian Jiang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Reinforcement Learning ◽

Symptom Severity ◽

Rating Scale ◽

Motor Symptom ◽

Sequential Decision ◽

Medication Regimen ◽

Severity Scores ◽

Decision Making Rule

AbstractOur objective is to derive a sequential decision-making rule on the combination of medications to minimize motor symptoms using reinforcement learning (RL). Using an observational longitudinal cohort of Parkinson’s disease patients, the Parkinson’s Progression Markers Initiative database, we derived clinically relevant disease states and an optimal combination of medications for each of them by using policy iteration of the Markov decision process (MDP). We focused on 8 combinations of medications, i.e., Levodopa, a dopamine agonist, and other PD medications, as possible actions and motor symptom severity, based on the Unified Parkinson Disease Rating Scale (UPDRS) section III, as reward/penalty of decision. We analyzed a total of 5077 visits from 431 PD patients with 55.5 months follow-up. We excluded patients without UPDRS III scores or medication records. We derived a medication regimen that is comparable to a clinician’s decision. The RL model achieved a lower level of motor symptom severity scores than what clinicians did, whereas the clinicians’ medication rules were more consistent than the RL model. The RL model followed the clinician’s medication rules in most cases but also suggested some changes, which leads to the difference in lowering symptoms severity. This is the first study to investigate RL to improve the pharmacological approach of PD patients. Our results contribute to the development of an interactive machine-physician ecosystem that relies on evidence-based medicine and can potentially enhance PD management.

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Progression of Nonmotor Symptoms in Parkinson’s Disease by Sex and Motor Laterality

Parkinson s Disease ◽

10.1155/2021/8898887 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Zimple Kurlawala ◽

Paul H. Shadowen ◽

Joseph D. McMillan ◽

Levi J Beverly ◽

Robert P. Friedland

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Symptom ◽

Motor Symptoms ◽

Healthy Controls ◽

Nonmotor Symptoms ◽

Start Up ◽

Progression Markers

Nonmotor symptoms (NMS) in Parkinson’s disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson’s Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson’s progressed. In conclusion, males experienced increased NMS burden in Parkinson’s disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients’ quality of life by therapeutically alleviating nonmotor symptoms.

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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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