What is the brain?

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By Dr. Georg Northoff, Canada Research Chair and Director of the Brain Imaging, Mind, and Neuroethics Clinical Research Unit at The Royal

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What is the brain?

  1. 1. What is the Brain? A Grey Pulpy Gruesome Device?
  2. 2. Brain as Behavioral-Cognitive Reflex Apparatus (Sherrington, Cognitive Neuroscience) Stimulus-induced activity : Complete and exclusive determination by the stimulus Brain itself has No SAY in what happens in the brain!
  3. 3. Brain as Active Player in its Neuronal Activity (Brown, Lashley, Llinas, Shulman, Panksepp) Stimulus-induced activity : Result of Rest-Stimulus Interaction Brain itself has a Strong SAY in what happens in the brain!
  4. 4. Is the Brain's Resting State Activity Relevant? For the Brain’s Function in Depression Doc/Postdoc Dave Hayes Christine Wiebking Oliver Lyttelton Niall Duncan Alexander Heinzel Bjoern Enzi Pengmin Qin Moritz deGreck Takashi Nakao Felix Bermpohl Simone Grimm Collaborations Jaak Panksepp Henning Scheich Peter Boesiger Rolf Koetter Bernhard Bogerts Gottfried Schlaug Alvaro Pascual-Leone Heinz Boeker Hans-Jochen Heinze Daniel Hell Stephan Heckers Universities Zuerich/ETH Zuerich/Psychiatrie Duesseldorf/Neuroanatomie Berlin/Psychiatrie Boston/Harvard/Neurologie Magdeburg/Neurologie New York/Psychologie Juelich/FZ Genf/Neurologie Washington/DC-NIH Hongkong/China Supported by: CRC, CIHR, Michael Smith Foundation, DFG, DAAD, BMBF, SNF, Krupp-Stiftung, Salus-Stiftung, GebertRüf Stiftung, Astra Zeneca, Lilly, Goldberg Foundation, Hope of Depression Research Foundation (HDRF/ISAN)
  5. 5. How is the abnormally high resting state activity in depression related to gaba- and glutamat-ergic receptors? A translational approach
  6. 6. Neuropsychological functions: Emotional perception versus Emotional judgment Neuroimage, 30(1):325-340, 2006
  7. 7. Deactivation (Negative BOLD Response) in depression: Baseline > Emotional perception in Healthy subjects > Depressed subjects L PCC L R R PACC/Cg25 Decreased deactivation or negative BOLD response (NBR) during emotional perception in ventromedial prefrontal cortex (VMPFC) in depression Grimm, Neuropsychopharmacology, 2009
  8. 8. Depressed subjects Healthy controls 0,5 % Signal Change PV PJ unPV unPJ exPV exPJ Ex ExE ExJ 0,6 PACC 0,4 % Signal Change VMPFC allPic 0,3 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 0,6 % Signal Change 0,5 VMPFC 0,4 0,3 % Signal Change PACC 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 0,6 % Signal Change 0,5 PCC 0,4 0,3 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 % Signal Change PCC 0,6 0,5 0,4 0,3 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 0,6 0,5 0,4 0,3 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 0,6 0,5 0,4 0,3 0,2 0,1 0 -0,1 -0,2 -0,3 -0,4 -0,5 -0,6 Grimm, Neuropsychopharmacology, 2009
  9. 9. Distinction between Self and Non-Self: Cortical midline structures and domain independence Neuroimage 31: 440-457, 2006
  10. 10. Self in Depression – Ruminations and Increased Self-focus Self in Healthy and Depression: Imaging Studies
  11. 11. Psychological relevance of Resting State activity: How is it generated biochemically [In collaboration with P.Boesiger/ETH Zuerich] = Lokalisation der MRS Northoff, Nature Neuroscience, 2007
  12. 12. GABA-ergic neuron Astrocyte Gln Glutamat-ergic neuron Gln GluSyn Glu Gln GluSyn Glu Glucose Glu Glucose Gaba Neuronal inhibition NBR: Negative BOLD response Neuronal excitation PBR: Positive BOLD response Vascular supply: OxyHB/DesoxyHB
  13. 13. Future Directions III: Resting State Abnormality as Endophenotype ???
  14. 14. Future Directions III: Resting State Abnormality as Bridge between molecular-genetic and behavioral-symptomatic level ????

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