• Home
• Staff & Students
• Vacancies

 

Hagai Bergman

 

Wednesday 2nd September 2015

Time: 4.00pm

 

Ground Floor Seminar Room

25 Howland Street, London, W1t 4JG

 

Computational physiology of the basal ganglia networks and of their disorders and therapy

 

Our computational model of the basal ganglia (BG) networks holds that the BG use actor/critics architecture to enable multi-objective optimization of fast, automatic and unconsciousness behavioral policy. The BG modulators (e.g., dopamine, ACh, 5-HT and histamine; critics) encode the mismatch between prediction and reality; whereas the BG funneling main axis (actor) extract the relevant (for action) information from the state-encoding cortical regions and handle it to the frontal cortex and brainstem motor centers.

Parkinson's disease (PD) is caused by the death of midbrain dopaminergic neurons (BG critics) and the consequent depletion of dopamine in the striatum – the input stage of the BG main axis (actor). Dopamine replacement therapy is therefore the first-line treatment of PD; but after 5-10 years most patients lose the pharmacological honeymoon, and many are referred to Deep Brain Stimulation (DBS) procedures.

We have studied the spiking and LFP activity in the basal ganglia of non-human primates before and after induction of dopamine depletion and Parkinsonian symptoms by the MPTP toxin, and in human PD patients undergoing DBS procedures. The results of these studies are in line with the funneling actor (modulation of single pallidal neuron by both emotional and motor cues, lack of correlation between pairs of neurons in the BG main axis) and critics (complementary encoding by midbrain dopaminergic neurons and striatal cholinergic neurons, positive signal correlation between neurons pairs in the BG critics) BG model. Synchronous oscillations of the neurons in the BG main axis (subthalamic nucleus, external and internal segments of the globus pallidus and substantia nigra reticulata) following striatal dopamine depletion is probably the reason for the clinical symptoms of PD in the MPTP treated monkeys and human PD patients.

Finally, we can adopt the multi-objective optimization strategies of the basal ganglia to treat their disorders. Today, DBS parameters are manually and intermittently adjusted. DBS methods are therefore poorly suited to cope with the fast neuronal and clinical dynamics of PD. Our studies of closed loop DBS in MPTP treated monkeys revealed that the Parkinsonian basal ganglia can be observed and controlled. Therefore, closed loop DBS could be an effective tool in the future treatment of basal ganglia related neurological and psychiatric disorders.

 

Bio

Hagai Bergman

Education and Academic Degrees:
1980 MSc – Hebrew university of Jerusalem, Jerusalem, Israel
1984: M.D., Ph.D. Technion, Israel institute of technology, Haifa, Israel
1984-1987: Post doctorate fellowship with Moshe Abeles, The Hebrew University, Jerusalem, Israel
1987-1990: Post doctorate fellowship with Mahlon DeLong, the Johns Hopkins hospital, Baltimore, MD, USA

Appointments/Positions/Awards/Distinctions:
• 1990 -2003: Lecturer, senior lecturer and associate professor, The Hebrew university of Jerusalem
• 2003- Present: Professor, The Hebrew university of Jerusalem
• The Simone and Bernard Guttman Chair in Brain Research
• Researcher, The Edmond and Lily Safra Center for Brain Sciences
• Researcher, Institute for Medical Research Israel-Canada (IMRIC)
• Recipient of the 2013 Rappaport Prize for Senior Israeli Researcher

Selected publications:
1. Bergman, Wichmann & DeLong, Reversal of Experimental Parkinsonism by Lesions of the Subthalamic Nucleus. Science. 249: 1436-1438, 1990
2. Bergman, Wichmann, Karmon & DeLong, The primate subthalamic nucleus: II. Neural activity in the subthalamic nucleus and pallidum in the MPTP model of Parkinsonism. J. of Neurophysiology. 72: 507-520, 1994
3. Nini, Feingold, Slovin & Bergman, Neurons in the globus pallidus do not show correlated activity in the normal monkey, but phase-locked oscillations appear in the MPTP model of Parkinsonism. J. of Neurophysiology. 74: 1800-1805, 1995
4. Raz, Feingold, Zelanskaya & Bergman, Neuronal synchronization of tonically active neurons in the striatum of normal and Parkinsonian primates. J. of Neurophysiology. 76(3): 2083-2088, 1996
5. Raz. Vaadia & Bergman, Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and tremulous MPTP Vervet model of Parkinsonism. J. Of Neuroscience, 20(22): 8559-8571, 2000
6. Bar-Gad, Heimer, Ritov & Bergman, Functional correlations between neighboring neurons in the primate Globus Pallidus are weak or nonexistent, J. of Neuroscience, 23(10): 4012-4016, 2003
7. Bar-Gad, Morris & Bergman, Information processing, dimensionality reduction and reinforcement learning in the basal ganglia; Progress In Neurobiology, 71(6), 439-473, 2003
8. Morris, Arkadir, Nevet, Vaadia & Bergman, Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons, Neuron, 43, 133-143, 2004
9. Joshua, Adler, Prut, Vaadia, Wickens and Bergman; Synchronization of midbrain dopaminergic neurons is enhanced by rewarding events; Neuron, 62, 695–704, 2009
10. Zaidel, Spivak, Grieb, Bergman &. Israel; Subthalamic span of beta-oscillations predicts deep brain stimulation efficacy for Parkinson’s patients, Brain 133(7), 2007-2021. 2010.
11. Parush, Tishby & Bergman, Dopaminergic balance between reward maximization and policy complexity, Frontiers in Systems Neuroscience, May 2011, 5, 22, 1-11
12. Rosin, Slovik, Mitelman, Rivlin-Etzion, Haber, Israel, Vaadia & Bergman; Closed-loop deep brain stimulation is superior in ameliorating Parkinsonism, Neuron, 72(2), 370-384, 2011