Uncoupling the roles of firing rates and spike bursts in shaping the STN-GPe beta band oscillations

Bahuguna, Jyotika; Sahasranamam, Ajith; Kumar, Arvind

doi:10.1371/journal.pcbi.1007748

Cited by 23 publications

(18 citation statements)

References 99 publications

(196 reference statements)

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“…However, a more recent study indicates that this abnormal neural dynamic is critically dependent on GPe rather than on cortex and STN (de la Crompe et al, 2020 ). In line with the above hypothesis, another new study has shown that the bursting of STN depends on the bursting of GPe neurons (Bahuguna et al, 2020 ). Taken together, we believe that the GPe-STN network is important in the maintenance and propagation of β synchronization.…”

Section: Main Textmentioning

confidence: 70%

“…Usually, β oscillation is not exaggerated until several days after 6-OHDA lesion (Mallet et al, 2008b ), suggesting it needs a long-term adaptive change of the synaptic alteration. There are many hypotheses concerning the generation and propagation of abnormal β oscillation activity in PD (Walters et al, 2007 ; Shouno et al, 2017 ; Bahuguna et al, 2020 ). Several studies have suggested that the intrinsic β oscillation in the GPe-STN network is too weak to act as a pacemaker and the β oscillation might be generated by cortex, and later amplified by the GPe-STN network (Brittain and Brown, 2014 ; Koelman and Lowery, 2019 ).…”

Section: Main Textmentioning

confidence: 99%

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Connectivity and Functionality of the Globus Pallidus Externa Under Normal Conditions and Parkinson's Disease

Dong

Hawes

et al. 2021

Front. Neural Circuits

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The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through the creation of complex connections with the other basal ganglia nuclei and brain regions. Recently, with the adoption of sophisticated genetic tools, substantial advances have been made in understanding the distinct molecular, anatomical, electrophysiological, and functional properties of GPe neurons and non-neuronal cells. Impairments in dopamine transmission in the basal ganglia contribute to Parkinson's disease (PD), the most common movement disorder that severely affects the patients' life quality. Altered GPe neuron activity and synaptic connections have also been found in both PD patients and pre-clinical models. In this review, we will summarize the main findings on the composition, connectivity and functionality of different GPe cell populations and the potential GPe-related mechanisms of PD symptoms to better understand the cell type and circuit-specific roles of GPe in both normal and PD conditions.

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Section: Main Textmentioning

confidence: 70%

Section: Main Textmentioning

confidence: 99%

Connectivity and Functionality of the Globus Pallidus Externa Under Normal Conditions and Parkinson's Disease

Dong

Hawes

et al. 2021

Front. Neural Circuits

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“…However, we speculate that besides the STN-GPe, the backprojections from GPe to striatum together with recurrent connections within the GPe can form an effective excitatory-inhibitory network necessary for generating oscillations. It is worth noting that previous experimental data (Mallet et al, 2006;de la Crompe et al, 2020;Sharott et al, 2017) and computational models (Kumar et al, 2011;Mirzaei et al, 2017;Bahuguna et al, 2020) provide a strong evidence that strengthening of D2-SPN→GPe-TI connection is also sufficient to induce βband oscillations/synchrony in the ongoing activity state of the BG. Thus, here, we provide a unified explanation of impaired transient response and ongoing activity in PD state.…”

Section: Discussionmentioning

confidence: 85%

“…While β-band oscillations are a clear neural signature of PD, the mechanisms underlying the emergence of these oscillations are still not understood. Both experimental data (Plenz and Kital, 1999;Hammond et al, 2007;Tachibana et al, 2011;de la Crompe et al, 2020) and computational models (Kumar et al, 2008;Tachibana et al, 2011;Holgado et al, 2010;Pavlides et al, 2015;Bahuguna et al, 2020) have implicated essentially all the various network interactions in generating oscillations. Here we have developed the BG model primarily to understand the transient response and found that the same model can also generate β-band oscillations.…”

Section: Effect Of Striato-pallaidal and Pallido-subthalamic Pathwaysmentioning

confidence: 99%

Transient response of basal ganglia network in healthy and low-dopamine state

Chakravarty

Roy

Sinha

et al. 2021

Preprint

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The basal ganglia (BG) are crucial for a variety of motor and cognitive functions. Changes induced by persistent low-dopamine (e.g. in Parkinson’s disease), result in aberrant changes in steady-state population activity (β-band oscillations) and transient response of the BG. Typically, brief cortical stimulation results in a triphasic response in the substantia nigra pars reticulata (SNr, output of the BG). The properties of the triphasic responses are shaped by dopamine levels. While it is relatively well understood how changes in BG result in aberrant steady state activity, it is not clear which BG interactions are crucial for the aberrant transient responses in the BG. Moreover, it is also not clear whether the same or different mechanisms underlie the aberrant changes in steady-state activity and aberrant transient response. Here we used numerical simulations of a network model of BG to identify the key factors that determine the shape of the transient responses. We show that an aberrant transient response of the SNr in low-dopamine state, involves changes in both, the direct pathway and the recurrent interactions within the globus pallidus externa (GPe) and between GPe and sub-thalamic nucleus. We found that the connections from D2-type spiny projection neurons to GPe are most crucial in shaping the transient response and by restoring them to their healthy level, we could restore the shape of transient response even in low-dopamine state. Finally, we show that the changes in BG that result in aberrant transient response are also sufficient to generate pathological oscillatory activity.Significance statementTo understand how changes induced by low-dopamine (e.g. in Parkinson’s disease, PD) affect basal ganglia (BG) function, we need to identify the factors that determine the shape of BG responses to brief cortical stimuli. We show that transient response of the BG is also affected by recurrent interactions within the subnuclei of the BG, and not just feedforward pathways. We found that input and local connectivity within the globus pallidus externa are crucial for shaping the transient response. We also show that the same network changes may underlie both, pathological β-band oscillations and aberrant transient responses. Our results highlight the importance of the recurrent connectivity within the BG and provide a coherent view of emergence of pathological activity in PD.

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“…However, reproducing the temporal patterning of beta oscillations has received little attention. It was reported very recently that spike bursting in a small proportion of neurons in the feedback loop formed by the STN and the globus pallidus pars externa (GPe) could contribute to transient beta oscillations [20]. Models of the STN-GPe feedback loop have been shown to generate Introducing average burst duration profiles.…”

Section: Introductionmentioning

confidence: 99%

Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson’s disease

Duchet

Ghezzi

Weerasinghe

et al. 2020

Preprint

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1Parkinson's disease motor symptoms are associated with an increase in subthalamic 2 nucleus beta band oscillatory power. But these oscillations are phasic, and there is a 3 growing body of evidence suggesting that beta burst duration may be of critical 4 importance to motor symptoms, making insights into the dynamics of beta bursting 5 generation valuable. In this study, we ask the question "Can average burst duration 6 reveal how dynamics change between the ON and OFF medication states?". Our 7 analysis of local field potentials from the subthalamic nucleus demonstrates using linear 8 surrogates that the system generating beta oscillations acts in a more non-linear regime 9 OFF medication and that the change in the degree of non-linearity is correlated with 10 motor impairment. Further, we pinpoint specific dynamical changes responsible for 11 changes in the temporal patterning of beta oscillations between medication states by 12 fitting to data biologically inspired models, and simpler beta envelope models. Finally, 13 we show that the non-linearity can be directly extracted from average burst duration 14 profiles under the assumption of constant noise in envelope models. This reveals that 15 average burst duration profiles provide a window into burst dynamics, which may 16 underlie the success of burst duration as a biomarker. In summary, we demonstrate a 17 relationship between average burst duration profiles, dynamics of the system generating 18 beta oscillations, and motor impairment, which puts us in a better position to 19 understand the pathology and improve therapies such as deep brain stimulation. 20 April 27, 2020 1/39 65 OFF medication states to changes in dynamical properties of the system generating 66 beta oscillations? 67In previous studies, STN beta bursts have been mostly studied based on one 68 arbitrary threshold of the beta envelope as events above the threshold, potentially with 69April 27, 2020 2/39 a minimum duration condition (examples of various thresholds shown in Fig 1A). 70Average burst duration and amplitude profiles describing the average burst duration 71 and amplitude for a range of thresholds (see Fig 1A and Fig 1B for an illustration of 72 average burst duration profiles) have been introduced [13,14]. However, they played a 73 minor role and have not been considered systematically on an individual patient basis. 74 Here, we leave behind the arbitrary choice of a threshold by relying on profiles across 75 thresholds to provide an unbiased characterisation of beta oscillation temporal 76 patterning. It has been established that STN beta burst duration is a better metric 77 than burst amplitude to distinguish between the healthy and pathological states in an 78 animal model of PD [19]. We begin our study by investigating in STN recordings of PD 79 patients whether average burst duration profiles are better at distinguishing between the 80 ON and OFF medication states than average burst amplitude profiles. We only observe 81 changes in temporal patterning of beta oscillations in...

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Uncoupling the roles of firing rates and spike bursts in shaping the STN-GPe beta band oscillations

Cited by 23 publications

References 99 publications

Connectivity and Functionality of the Globus Pallidus Externa Under Normal Conditions and Parkinson's Disease

Connectivity and Functionality of the Globus Pallidus Externa Under Normal Conditions and Parkinson's Disease

Transient response of basal ganglia network in healthy and low-dopamine state

Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson’s disease

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