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

1
Firing rates, patterns and oscillatory activity
in basal ganglia in movement disorder patients

• Jonathan Dostrovsky
• Department of Physiology
• University of Toronto

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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

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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.

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Dostrovsky
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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

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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

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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?

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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

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GPe
GPie
GPii
OT
Dostrovsky
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Firing rates

• PD vs cervical dystonia, and HD
• PD vs generalized dystonia
• Effect of propofol in dystonia patients

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Dostrovsky
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G1 secondary hemidystonia G2 DYT1 G3
secondary gen G4 - idiopathic
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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
  Huntingtons disease

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Dostrovsky
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Poisson surprise - Percent spikes in bursts
Dostrovsky
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Firing pattern in comparison with poisson
distribution
Dostrovsky
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Firing pattern based on autocorrelogram shape
Dostrovsky
Dostrovsky
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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).

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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

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Effect of apomorphine on neuronal firing rates in
GP
Dostrovsky
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Apomorphine on STN neurons
Levy, R., et al. Brain 125 1196-1209, 2002
J.Neurophysiol. 2001
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Firing pattern
Receptive field size
Levy, R., et al. J.Neurophysiol. 2001
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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

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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

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Three types or rhythmic firing in STN
Levy, R., et al. J. Neuroscience 20 7766-7775,
2000
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Levy, R., et al. J. Neuroscience 20 7766-7775,
2000
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X correlogram and coherence analysis from pairs
of neurons in STN
Levy, R., et al. J. Neuroscience 20 7766-7775,
2000
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Globus pallidus
The Journal of Neuroscience, April 1, 2002,
22(7)28552861
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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

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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

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Movement
Firing rate 1
Firing rate 2
Power spectrum 1
Power spectrum 2
Coherence
Levy, R., et al. Brain 125 1196-1209, 2002
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Firing rate 1
Firing rate 2
Power spectrum 1
Power spectrum 2
Coherence
Phase
Levy, R., et al. Brain 125 1196-1209, 2002
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Simultaneous recording of local field potential
and STN neuron activity
Levy, R., et al. Brain 125 1196-1209, 2002
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Levy, R., et al. Brain 125 1196-1209, 2002
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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

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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.

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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

Supported by CIHR and NIH