Leonid Rubchinsky

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  Optogenetic vs. electrical stimulation effects on synchronized oscillations of neural activity
  Leonid Rubchinsky

  Deep brain stimulation (DBS) is used as a therapeutic procedure to treat symptoms of several neurological and neuropsychiatric disorders by controlling electrical activity of neural circuits. In particular it is used to treat motor symptoms of Parkinson’s disease (PD), associated with excessive oscillatory synchronized activity in the beta frequency band. An alternative way to stimulate neural circuits is an emerging technology of optogenetics. It is not clear when/if optogenetics will eventually be possible to implement in clinical practice. However, it is emerging as a widely used experimental tool to control brain networks. Thus, the goal of his study is to explore how effective an optogenetic stimulation in comparison with electrical stimulation in their network effects on elevated synchronized oscillatory activity. We use a computational model of subthalamic and pallidal circuits, which was developed to reproduce experimentally observed beta-band activity patterns. We model electrical stimulation as well as optogenetic stimulation of two types (excitatory via channelrhodopsin and inhibitory via halorodopsin). All three modes of stimulation can decrease beta synchrony. The actions of different stimulation types on the beta activity differ from each other. Electrical DBS and optogenetic excitation have somewhat similar effects on the network. They both cause desynchronization and suppression of the beta-band bursting. As intensity of stimulation is growing, they synchronize the network at higher (non-beta) frequencies in almost tonic dynamics. Optogenetic inhibition effectively reduces spiking and bursting activity of the targeted neurons. We compare the stimulation modes in terms of the minimal effective current delivered to basal ganglia neurons in order to suppress beta activity below a threshold. Optogenetic inhibition usually requires less effective current than electrical DBS to achieve beta suppression. Optogenetic excitation, while as not efficacious as optogenetic inhibition, still usually requires less effective current than electrical DBS to suppress beta activity. Our results suggest that optogenetic stimulation may introduce smaller effective currents than conventional electrical DBS, but still achieve sufficient beta activity suppression. Thus, optogenetic stimulation may be more effective than electrical stimulation in control of synchronized oscillatory neural activity because of the different ways of how stimulations interact with network dynamics.

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  Temporal patterns of intermittent neural synchronization
  Leonid Rubchinsky

  Synchronization of neural activity in the brain is involved in a variety of brain functions including perception, cognition, memory, and motor behavior. Excessively strong, weak, or otherwise improperly organized patterns of synchronous oscillatory activity appear to contribute to the generation of symptoms of different neurological and psychiatric diseases. However, neuronal synchrony is frequently not perfect, but rather exhibits intermittent dynamics. So the same synchrony strength may be achieved with markedly different temporal patterns of activity (roughly speaking oscillations may go out of the synchronous state for many short episodes or few long episodes). I will discuss this situation from two perspectives: the phase-space perspective and associated considerations of dynamical systems theory and time-series analysis perspective. I will then proceed with the application of this analysis to the neurophysiological data in healthy brain, Parkinson's disease, and in drug addiction disorders.

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  Synchronized oscillations in cortico-basal ganglia circuits in Parkinson's disease
  Leonid Rubchinsky

  Motor symptoms of Parkinson's disease have been associated with the synchronized oscillatory activity in the cortico-basal ganglia-thalamic circuits. Here we will present our observations of the patterns of synchronized activity obtained through simultaneous intraoperative recordings of spikes and LFP in the basal ganglia and cortical EEG in parkinsonian patients. We discuss the temporal patterning of the observed synchronized patterning. We show how the synchronization of EEG in motor and prefrontal areas (which can be obtained noninvasively) is predictive of the spike-LFP synchrony in subthalamic nucleus. We also consider the observed phenomena within the framework of mathematical models of cortico-basal ganglia circuits.