Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

Electrophysiological biomarkers reflecting the pathological activities in the basal ganglia are essential to gain an etiological understanding of Parkinson′s disease (PD) and develop a method of diagnosing and treating the disease. Previous studies that explored electrophysiological biomarkers in PD have focused mainly on oscillatory or periodic activities such as beta and gamma oscillations. Emerging evidence has suggested that the nonoscillatory, aperiodic component reflects the firing rate and synaptic current changes corresponding to cognitive and pathological states. Nevertheless, it has never been thoroughly examined whether the aperiodic component can be used as a biomarker that reflect pathological activities in the basal ganglia in PD. In this study, we examined the parameters of the aperiodic component and tested its practicality as an electrophysiological biomarker of pathological activity in PD. We found that a set of aperiodic parameters, aperiodic offset and exponent, were significantly decreased by the nigrostriatal lesion. To further prove the usefulness of the parameters as biomarkers, acute levodopa treatment reverted the aperiodic offset. We then compared the aperiodic parameters with a previously established periodic biomarker of PD, beta frequency oscillation. We found a moderately significant negative correlation with beta power. Finally, taking the aperiodic parameters into account, we could significantly improve the beta power-based prediction of pathological activities in the basal ganglia, demonstrating the validity of these parameters as biomarkers.

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Aberrant striatal oscillations after dopamine loss in parkinsonian non-human primates

10.1101/650770 ◽

2019 ◽

Cited By ~ 1

Author(s):

Arun Singh ◽

Stella M. Papa

Keyword(s):

Basal Ganglia ◽

Oscillatory Activity ◽

Field Potentials ◽

Striatal Neurons ◽

Dopamine Depletion ◽

Frequency Bands ◽

Oscillatory Pattern ◽

Motor Abnormalities ◽

Beta Frequency

AbstractDopamine depletion in Parkinson’s disease (PD) is associated with abnormal oscillatory activity in the cortico-basal ganglia network. However, the oscillatory pattern of striatal neurons in PD remains poorly defined. Here, we analyzed the local field potentials in one untreated and five MPTP-treated non-human primates (NHP) to model advanced PD. Augmented oscillatory activity in the alpha (8-13 Hz) and low-beta (13-20 Hz) frequency bands was found in the striatum in parallel to the motor cortex and globus pallidus of the NHP-PD model. The coherence analysis showed increased connectivity in the cortico-striatal and striato-pallidal pathways at alpha and low-beta frequency bands, confirming the presence of abnormal 8-20 Hz activity in the cortico-basal ganglia network. The acute L-Dopa injection that induced a clear motor response normalized the amplified 8-20 Hz oscillations. These findings indicate that pathological striatal oscillations at alpha and low-beta bands are concordant with the basal ganglia network changes after dopamine depletion, and thereby support a key role of the striatum in the generation of parkinsonian motor abnormalities.

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Modulation of dopamine tone induces frequency shifts in cortico-basal ganglia beta oscillations

Nature Communications ◽

10.1038/s41467-021-27375-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

L. Iskhakova ◽

P. Rappel ◽

M. Deffains ◽

G. Fonar ◽

O. Marmor ◽

...

Keyword(s):

Basal Ganglia ◽

Phase Locking ◽

Oscillatory Activity ◽

Dopamine Depletion ◽

Beta Oscillations ◽

Strongly Coupled ◽

Beta Power ◽

Oscillatory Power ◽

Phase Amplitude ◽

Beta Frequency

AbstractΒeta oscillatory activity (human: 13–35 Hz; primate: 8–24 Hz) is pervasive within the cortex and basal ganglia. Studies in Parkinson’s disease patients and animal models suggest that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine tone remains unclear. We recorded neural activity in the cortex and basal ganglia of healthy non-human primates while acutely and chronically up- and down-modulating dopamine levels. We assessed changes in beta oscillations in patients with Parkinson’s following acute and chronic changes in dopamine tone. Here we show beta oscillation frequency is strongly coupled with dopamine tone in both monkeys and humans. Power, coherence between single-units and local field potentials (LFP), spike-LFP phase-locking, and phase-amplitude coupling are not systematically regulated by dopamine levels. These results demonstrate that beta frequency is a key property of pathological oscillations in cortical and basal ganglia networks.

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Dynamic Changes in the Cortex-Basal Ganglia Network After Dopamine Depletion in the Rat

Journal of Neurophysiology ◽

10.1152/jn.90466.2008 ◽

2008 ◽

Vol 100 (1) ◽

pp. 385-396 ◽

Cited By ~ 56

Author(s):

Cyril Dejean ◽

Christian E. Gross ◽

Bernard Bioulac ◽

Thomas Boraud

Keyword(s):

Basal Ganglia ◽

Local Field ◽

Signal Transmission ◽

Local Field Potentials ◽

Cellular Level ◽

Cortical Activation ◽

Field Potentials ◽

Dopamine Depletion ◽

Indirect Pathway ◽

Before And After

It is well established that parkinsonian syndrome is associated with alterations in the temporal pattern of neuronal activity and local field potentials in the basal ganglia (BG). An increase in synchronized oscillations has been observed in different BG nuclei in parkinsonian patients and animal models of this disease. However, the mechanisms underlying this phenomenon remain unclear. This study investigates the functional connectivity in the cortex-BG network of a rodent model of Parkinson's disease. Single neurons and local field potentials were simultaneously recorded in the motor cortex, the striatum, and the substantia nigra pars reticulata (SNr) of freely moving rats, and high-voltage spindles (HVSs) were used to compare signal transmission before and after dopaminergic depletion. It is shown that dopaminergic lesion results in a significant enhancement of oscillatory synchronization in the BG: the coherence between pairs of structures increased significantly and the percentage of oscillatory auto- and cross-correlograms. HVS episodes were also more numerous and longer. These changes were associated with a shortening of the latency of SNr response to cortical activation, from 40.5 ± 4.8 to 10.2 ± 1.07 ms. This result suggests that, in normal conditions, SNr neurons are likely to be driven by late inputs from the indirect pathway; however, after the lesion, their shorter latency also indicates an overactivation of the hyperdirect pathway. This study confirms that neuronal signal transmission is altered in the BG after dopamine depletion but also provides qualitative evidence for these changes at the cellular level.

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Frequency matters: Up- and Down-Regulation of Dopamine Tone Induces Similar Frequency Shifts in Cortico-Basal Ganglia Beta Oscillations

10.1101/2020.12.14.422621 ◽

2020 ◽

Author(s):

L. Iskhakova ◽

P. Rappel ◽

G. Fonar ◽

O. Marmor ◽

R. Paz ◽

...

Keyword(s):

Basal Ganglia ◽

Phase Locking ◽

Oscillatory Activity ◽

Dopamine Depletion ◽

Beta Oscillations ◽

Similar Frequency ◽

Strongly Coupled ◽

Beta Power ◽

Oscillatory Power ◽

Network Studies

AbstractBeta oscillatory activity (13-30Hz) is pervasive within the cortico-basal ganglia (CBG) network. Studies in Parkinson’s disease (PD) patients and animal models suggested that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine-tone remains unclear. We recorded neural activity in the CBG network of non-human-primates (NHP) while acutely up- and down-modulating dopamine levels. Further, we assessed changes in beta oscillations of PD patients following acute and chronic changes in dopamine-tone. Beta oscillation frequency was strongly coupled with dopamine-tone in both NHPs and human patients. In contrast, power, coherence between single-units and LFP, and spike-LFP phase-locking were not systematically regulated by dopamine levels. These results demonstrate via causal manipulations that frequency, rather than other properties, is the key property of pathological oscillations in the CBG networks. These insights can lead to improvements in understanding of CBG physiology, PD progression tracking and patient care.

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The rate of transient beta frequency events predicts behavior across tasks and species

eLife ◽

10.7554/elife.29086 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 78

Author(s):

Hyeyoung Shin ◽

Robert Law ◽

Shawn Tsutsui ◽

Christopher I Moore ◽

Stephanie R Jones

Keyword(s):

High Power ◽

Event Rate ◽

Brain Activity ◽

Detection Task ◽

Field Potentials ◽

Motor Action ◽

Attention Tasks ◽

Beta Power ◽

Beta Frequency ◽

Abnormal Behaviors

Beta oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of healthy and abnormal behaviors, including perception, attention and motor action. In non-averaged signals, beta can emerge as transient high-power 'events'. As such, functionally relevant differences in averaged power across time and trials can reflect changes in event number, power, duration, and/or frequency span. We show that functionally relevant differences in averaged beta power in primary somatosensory neocortex reflect a difference in the number of high-power beta events per trial, i.e. event rate. Further, beta events occurring close to the stimulus were more likely to impair perception. These results are consistent across detection and attention tasks in human magnetoencephalography, and in local field potentials from mice performing a detection task. These results imply that an increased propensity of beta events predicts the failure to effectively transmit information through specific neocortical representations.

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Propagation of beta/gamma rhythms in the cortico-basal ganglia circuits of the parkinsonian rat

Journal of Neurophysiology ◽

10.1152/jn.00629.2017 ◽

2018 ◽

Vol 119 (5) ◽

pp. 1608-1628 ◽

Cited By ~ 19

Author(s):

Timothy O. West ◽

Luc Berthouze ◽

David M. Halliday ◽

Vladimir Litvak ◽

Andrew Sharott ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Reference Signal ◽

Motor Impairment ◽

Gamma Oscillations ◽

Hierarchical Organization ◽

Directed Network ◽

Dopamine Depletion ◽

High Beta

Much of the motor impairment associated with Parkinson’s disease is thought to arise from pathological activity in the networks formed by the basal ganglia (BG) and motor cortex. To evaluate several hypotheses proposed to explain the emergence of pathological oscillations in parkinsonism, we investigated changes to the directed connectivity in BG networks following dopamine depletion. We recorded local field potentials (LFPs) in the cortex and basal ganglia of rats rendered parkinsonian by injection of 6-hydroxydopamine (6-OHDA) and in dopamine-intact controls. We performed systematic analyses of the networks using a novel tool for estimation of directed interactions (nonparametric directionality, NPD). We used a “conditioned” version of the NPD analysis that reveals the dependence of the correlation between two signals on a third reference signal. We find evidence of the dopamine dependency of both low-beta (14–20 Hz) and high-beta/low-gamma (20–40 Hz) directed network interactions. Notably, 6-OHDA lesions were associated with enhancement of the cortical “hyperdirect” connection to the subthalamic nucleus (STN) and its feedback to the cortex and striatum. We find that pathological beta synchronization resulting from 6-OHDA lesioning is widely distributed across the network and cannot be located to any individual structure. Furthermore, we provide evidence that high-beta/gamma oscillations propagate through the striatum in a pathway that is independent of STN. Rhythms at high beta/gamma show susceptibility to conditioning that indicates a hierarchical organization compared with those at low beta. These results further inform our understanding of the substrates for pathological rhythms in salient brain networks in parkinsonism. NEW & NOTEWORTHY We present a novel analysis of electrophysiological recordings in the cortico-basal ganglia network with the aim of evaluating several hypotheses concerning the origins of abnormal brain rhythms associated with Parkinson’s disease. We present evidence for changes in the directed connections within the network following chronic dopamine depletion in rodents. These findings speak to the plausibility of a “short-circuiting” of the network that gives rise to the conditions from which pathological synchronization may arise.

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A Beta Oscillation Network in the Rat Olfactory System During a 2-Alternative Choice Odor Discrimination Task

Journal of Neurophysiology ◽

10.1152/jn.00166.2010 ◽

2010 ◽

Vol 104 (2) ◽

pp. 829-839 ◽

Cited By ~ 55

Author(s):

Leslie M. Kay ◽

Jennifer Beshel

Keyword(s):

Frequency Band ◽

Field Potential ◽

Gamma Oscillations ◽

Beta Band ◽

Beta Oscillations ◽

Odor Discrimination Task ◽

Beta Power ◽

Beta Frequency Band ◽

Alternative Choice ◽

Beta Frequency

We previously showed that in a two-alternative choice (2AC) task, olfactory bulb (OB) gamma oscillations (∼70 Hz in rats) were enhanced during discrimination of structurally similar odorants (fine discrimination) versus discrimination of dissimilar odorants (coarse discrimination). In other studies (mostly employing go/no-go tasks) in multiple labs, beta oscillations (15–35 Hz) dominate the local field potential (LFP) signal in olfactory areas during odor sampling. Here we analyzed the beta frequency band power and pairwise coherence in the 2AC task. We show that in a task dominated by gamma in the OB, beta oscillations are also present in three interconnected olfactory areas (OB and anterior and posterior pyriform cortex). Only the beta band showed consistently elevated coherence during odor sniffing across all odor pairs, classes (alcohols and ketones), and discrimination types (fine and coarse), with stronger effects in first than in final criterion sessions (>70% correct). In the first sessions for fine discrimination odor pairs, beta power for incorrect trials was the same as that for correct trials for the other odor in the pair. This pattern was not repeated in coarse discrimination, in which beta power was elevated for correct relative to incorrect trials. This difference between fine and coarse odor discriminations may relate to different behavioral strategies for learning to differentiate similar versus dissimilar odors. Phase analysis showed that the OB led both pyriform areas in the beta frequency band during odor sniffing. We conclude that the beta band may be the means by which information is transmitted from the OB to higher order areas, even though task specifics modify dominance of one frequency band over another within the OB.

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Basal ganglia local field potentials: applications in the development of new deep brain stimulation devices for movement disorders

Expert Review of Medical Devices ◽

10.1586/17434440.4.5.605 ◽

2007 ◽

Vol 4 (5) ◽

pp. 605-614 ◽

Cited By ~ 46

Author(s):

Sara Marceglia ◽

Lorenzo Rossi ◽

Guglielmo Foffani ◽

AnnaMaria Bianchi ◽

Sergio Cerutti ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Basal Ganglia ◽

Local Field ◽

Brain Stimulation ◽

Movement Disorders ◽

Local Field Potentials ◽

Field Potentials ◽

Deep Brain

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Neuro-Cognitive Profile of Morning and Evening Chronotypes at Different Times of Day

Annals of Neurosciences ◽

10.1177/0972753121990280 ◽

2021 ◽

pp. 097275312199028

Author(s):

Nanditha Venkat ◽

Meenakshi Sinha ◽

Ramanjan Sinha ◽

Jayshri Ghate ◽

Babita Pande

Keyword(s):

Statistical Tests ◽

Power Spectral Analysis ◽

Significant Negative Correlation ◽

Cognitive Status ◽

Event Related Potential ◽

Fast Fourier Transformation ◽

P300 Latency ◽

Cognitive Measures ◽

Circadian Time ◽

Beta Power

Background: Chronotype is the circadian time preference for sleep–wake timings. However, its impact on cognitive performance is least explored. Objective: The present study investigated the effect of chronotype (morning “M” vs. evening “E”) on cognitive measures as a function of time of the day. In addition, the correlation between electroencephalogram (EEG) waves and subjective/objective cognitive measures were investigated. Method: Cognitive status of 28 adult male subjects (15 “M” and 13 “E”) was assessed objectively through event-related potential (ERP) by administering visual odd ball paradigm test and subjectively through Montreal Cognitive Assessment questionnaire. In addition, 20 to 30 min of resting EEG was recorded. Recordings were done from 8 to 10 am and from 4 to 6 pm on a single day. Power spectral analysis of EEG for alpha and beta waves at PZ and FZ cortical sites was done after subjecting selected epochs to fast Fourier transformation. Also, latency and amplitude of P300 potential from event-related potential record were measured. Appropriate statistical tests were applied for analysis. Results: Higher alpha and beta power was observed in “E” at PZ in the evening. “M” showed increased P300 latency and amplitude during evening session for frequent and rare stimuli and vice versa in “E.”’ Significant negative correlation was seen between latency of rare stimuli and alpha and beta power at FZ site during evening in “E” chronotype only. Conclusion: Result indicates better attention and alertness during evening hours in evening chronotypes and vice versa in morning chronotypes. The findings could be implemented to schedule the mental performance/cognitive load according to individual chronotype.

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Changes in excitability properties of ventromedial motor thalamic neurons in 6-OHDA lesioned mice

10.1101/2020.10.05.327379 ◽

2020 ◽

Author(s):

Edyta K Bichler ◽

Francesco Cavarretta ◽

Dieter Jaeger

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Potassium Current ◽

Cellular Level ◽

Inhibitory Input ◽

Dopamine Depletion ◽

Thalamic Nuclei ◽

Adult Mice ◽

Motor Thalamus

AbstractThe activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions have not be investigated at the cellular level. Such changes may well be expected due to homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-OHDA treated adult mice. At a minimum of 1 month post 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily due to a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in basal ganglia thalamocortical processing in Parkinson’s disease.Significance StatementOur investigation of the excitability properties of neurons in the basal ganglia input receiving motor thalamus (BGMT) is significant because they are likely to be different from properties in other thalamic nuclei due to the additional inhibitory input stream these neurons receive. Further, they are important to understand the role of BGMT in the dynamic dysfunction of cortico – basal ganglia circuits in Parkinson’s disease. We provide clear evidence that after 6-OHDA treatment of mice important homeostatic changes occur in the intrinsic properties of BGMT neurons. Specifically we identify the M-type potassium current as an important thalamic excitability regulator in the parkinsonian state.

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