Mechanisms of deep brain stimulation: exploring resonance and stimulation-induced decoupling - Archive ouverte HAL
Communication Dans Un Congrès Année : 2008

Mechanisms of deep brain stimulation: exploring resonance and stimulation-induced decoupling

Résumé

Recently, deep brain stimulation (DBS) has become a standard symptomatic procedure for Parkinson's disease (PD) and other movement and psychiatric disorders. Despite its success, the effect of this invasive and costly procedure is not completely understood. Indeed, how high-frequency, electrical stimulation of the subthalamic nucleus (STN) in the basal ganglia improves symptoms is not known. Furthermore, DBS raises several interesting paradoxes: it mimics the effects of a lesion, improves symptoms when the frequency is >100 Hz whereas low-frequency DBS has no effect or even worsens symptoms. In order to reconcile these various paradoxes, we explore the complex formed by the STN and the external segment of the Globus Pallidus (GPe) with a computational model. We investigate the possibility that DBS induces a functional decoupling between STN neurons. First, we develop neuronal models for STN and GPe neurons based on the Izhikevich model. Second, we derive population equations for the STN-GPe complex including connectivity and time delays. Third, we explore the dynamical behaviour of this model under different connectivity patterns. Finally, we apply a DBS current to the STN at different frequencies. Our simulation results suggest that STN-GPe complex can exhibit two different dynamical states: 1) a stable state, where both nuclei have a low and stable activity (physiological condition), or 2) an oscillatory activity where both nuclei exhibit low-frequency (systematically below 10 Hz) synchronized bursts of activity (pathological condition). Thus, activity at low frequencies appears to be intrinsic to the STN-GPe complex when it becomes disrupted. Consequently, we propose that low-frequency (below 20 Hz) DBS is ineffective, or even enhances pathological activity in the STN-GPe complex, because it resonates with the intrinsic frequency of the STN-GPe complex. Furthermore, we test the hypothesis that DBS causes a “stimulation-induced decoupling” (SID) between STN neurons, i.e., that individual dynamics of STN neurons become dominant compared to neuronal interactions within the STN. Thus, we simulate the activity of the STN-GPe complex with pathological dynamics, and apply a high-frequency DBS current to the STN. Our results show a high degree of similarity, whether there were recurrent connections in the STN or not. This suggests that DBS “isolates” neurons from one another, and breaks the relay of activity throughout and within the STN. Thus: 1) At the cellular level, high-frequency DBS prevents the generation of synchronized, low-frequency activity within the STN, 2) At the network level, this weakens the impact of cortical feedback to the STN and 3) At the motor feedback loop level (linking functionally cortex, basal ganglia and thalamus), the loop “opens”, as in the case of subthalamotomy. In summary, based on our results, we suggest that the difference in motor improvement between low and high frequency DBS is due to resonance phenomena between DBS current frequency and STN-GPe intrinsic frequency respectively. Furthermore, we suggest that SID is a plausible physiological mechanism for DBS which reconciles the paradox between stimulation and lesion effects and between excitation and/or inhibition of the STN. For the first time, this mechanism proposes a comprehensive multiscale (cellular, network, feedback loop) explanation of the effects of DBS in PD.
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Dates et versions

hal-00327526 , version 1 (08-10-2008)

Identifiants

  • HAL Id : hal-00327526 , version 1

Citer

J. Modolo, Anne Beuter. Mechanisms of deep brain stimulation: exploring resonance and stimulation-induced decoupling. Research in Encoding and Decoding of Neural Ensembles, Jun 2008, Santorini, Greece. pp.79. ⟨hal-00327526⟩
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