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Firing rates, patterns and oscillatory activity in basal ganglia in movement disorder patients

Outline of talk. Functional stereotactic neurosurgery and DBSReason and justification for recordings during stereotactic surgeryBrief description of technique Physiological findings used for target selectionStudies in basal gangliaFiring rates and patterns of neurons in GPi of Parkinson, Huntin

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Firing rates, patterns and oscillatory activity in basal ganglia in movement disorder patients

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    1. Firing rates, patterns and oscillatory activity in basal ganglia in movement disorder patients Jonathan Dostrovsky Department of Physiology University of Toronto

    2. Outline of talk Functional stereotactic neurosurgery and DBS Reason and justification for recordings during stereotactic surgery Brief description of technique Physiological findings used for target selection Studies in basal ganglia Firing rates and patterns of neurons in GPi of Parkinson, Huntington and dystonia patients. Effects of apomorphine Rhythmic firing and synchronicity in basal ganglia Effects of movements and apomorphine on beta oscillations

    3. Stereotactic surgery Surgery at sites deep within the brain utilizing a stereotactic frame and stereotactic coordinates. Used for making a lesion or implanting a DBS electrode in thalamus or basal ganglia for treatment of movement disorders (PD, dystonia, ET), pain, etc.

    5. Functional stereotactic surgery Use of physiological properties of target and surrounding areas to aid in localizing the target recordings of neural activity with microelectrode effects of stimulation through electrode mapping – multiple tracks Provides unique opportunity to study human brain in awake state Permits assessment of pathophysiology

    6. Methods Stereotactic frame, MRI scan, initial target selection Microelectrode recordings and microstimulation in awake patients Dual electrode setup for dual recordings, stimulation and/or drug injection The observations I will summarize were obtained during functional stereotactic surgery for alleviation of chronic pain or movement disorders. As part of the procedure we employ microelectrode recordings and microstimulation through these electrodes to localize the target. These recordings allow us to observe firing patterns, responses to sensory inputs, and the perceptual effects of artificially exciting the neurons at the electrode tip. By reconstructing the findings obtained through several parallel electrode tracks we can also get information about the somatotopic representation in the ventrobasal complex.The observations I will summarize were obtained during functional stereotactic surgery for alleviation of chronic pain or movement disorders. As part of the procedure we employ microelectrode recordings and microstimulation through these electrodes to localize the target. These recordings allow us to observe firing patterns, responses to sensory inputs, and the perceptual effects of artificially exciting the neurons at the electrode tip. By reconstructing the findings obtained through several parallel electrode tracks we can also get information about the somatotopic representation in the ventrobasal complex.

    7. Basal Ganglia studies – 5 Questions Are firing rates in GPi and STN elevated in PD and reduced in dystonia and Huntington disease? Are firing patterns altered in these conditions? Does dopaminergic therapy reverse hypothesized changes in firing rate in GP and STN in PD? Do STN neurons fire in an oscillatory pattern and how do these relate to tremor and local field potentials? Is there increased synchronization of GP and STN neurons in PD?

    8. Basal Ganglia studies Firing rates and patterns of neurons in globus pallidus internus of Parkinson, Huntington and dystonia patients. Effects of apomorphine Rhythmic firing and synchronicity in basal ganglia Effects of movements and apomorphine on oscillatory activity

    10. Firing rates PD vs cervical dystonia, and HD PD vs generalized dystonia Effect of propofol in dystonia patients

    13. Firing patterns What to measure? coefficient of variation, burst index, interspike interval histogram, skewness, kurtosis relation to poisson distribution Kaneoke and Vitek poisson surprise of Legendy and Salcman autorcorrelogram, spectral analysis PD vs cervical dystonia, generalized dystonia and Huntington’s disease

    18. Summary – rates and patterns Firing rates of GPi neurons in PD, HD and GD are not significantly different. GPi rates in CD lower. Firing patterns of GPi neurons in PD are generally different than in CD, GD, and HD, especially in GPii, but depend on method. GPii neuron firing in CD more ‘bursty’ than PD Propofol anesthesia decreases GPi firing rates and increases burstiness (BI).

    19. Basal Ganglia studies Firing rates and patterns of neurons in globus pallidus internus of Parkinson, Huntington and dystonia patients. Effects of apomorphine Rhythmic firing and synchronicity in basal ganglia Effects of movements and apomorphine on oscillatory activity

    20. Effect of apomorphine on neuronal firing rates in GP

    23. Summary - apomorphine Decreased firing rates in GPii and GPie Increased firing rates in GPe No overall change in mean STN firing rates Increased bursting in GP and STN Decrease in # and size of receptive fields Decrease in # of tremor cells

    24. Basal Ganglia studies Firing rates and patterns of neurons in globus pallidus internus of Parkinson, Huntington and dystonia patients. Effects of apomorphine Rhythmic firing and synchronicity in basal ganglia Effects of movements and apomorphine on oscillatory activity

    29. Brief summary of results Oscillatory firing in GPi and STN generally only seen in patients with tremor Oscillation frequency is at tremor frequency and/or in the 15 – 30Hz ß range Cross correlograms of rhythmically firing neurons are usually coherent and in phase in 15-30Hz range, but can be out of phase for tremor frequency Positive cross correlations and coherence only seen for oscillatory activity. No short latency correlations in GPi or STN. None seen in 10 pairs of SNr cells

    30. Basal Ganglia studies Firing rates and patterns of neurons in globus pallidus internus of Parkinson, Huntington and dystonia patients. Effects of apomorphine Rhythmic firing and synchronicity in basal ganglia Effects of movements and apomorphine on oscillatory activity in STN

    35. Brief summary of results Coherence and power in 15 – 30Hz range is decreased during movement and dopaminergic medication. Rhythmic firing in ß band is coherent with local field potential. ß band local field potential (recorded from DBS electrode contacts) is decreased during movements ß band local field potential decreased in ‘ON’ state

    36. Conclusions Firing rate results fail to support predictions of ‘rate’ model regarding hypo and hyperkinetic disorders, although apomorphine data are consistent. Firing patterns differ in different movement disorders There is a strong relationship between ß band oscillations and tremor as well as between movement and of levodopa Parkinsonian symptoms do not appear to be mediated by increased synchronization within GPi and STN.

    37. Acknowledgements Co-Investigators Bill Hutchison Peter Ashby Andres Lozano Tony Lang Graduate students Ron Levy Joyce Tang Research Assistants Vanessa Palter Helen Belina Sumit Das

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