CHALLENGING THE CONCEPTS OF LOCALIZATION AND RECOVERY OF BRAIN FUNCTION ReCBIR – Research Centre for Brain Injury Rehabilitation UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation UCN - The Unit for Cognitive Neuroscience Neuroplasticitet og rehabilitering efter hjerneskade – plasticitet i den intakte og skadede hjerne Jesper Mogensen, Professor Head of UCN (The Unit for Cognitive Neuroscience), Dep. of Psychol., University of Copenhagen Director of ReCBIR (Research Centre for Brain Injury Rehabilitation)

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 22 The Unit for Cognitive Neuroscience (UCN) The Brain Injury Unit of the Dep. of Neurorehabilitation Centre for Cognitive Neuroscience, University of Turku, FIN The Center for Rehabilitation of Brain Injury, Copenhagen Department of Rehabilitation Medicine, Charles University, Prag, CZ Trinity College Institute of Neuroscience, Trinity College, Dublin, IR Laboratory of Neuroplasticity, Nencki Institute, Warsaw, PL Medical Research Council, Cognition and Brain Sciences Unit, UK Glostrup Hospital Depts. of Neurol. and Neurosurg.

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 3 Fra FORTVIVLELSE - til HÅB

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 4 BEHANDLING af og STØTTE til patienterne: - større og bedre indsats nu - OG en forskning, som lægger grunden for fremtidens behandling

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 5 Hvad står i vejen for den bedre fremtid ? - dårlig økonomi - ”politisk” modstand (ledende til økonomiske hindringer)

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 6 Er rehabilitering efter hjerneskade ”uvidenskabelig” ? - nej - men hvordan kan hjernens funktioner både være ”lokaliserede” og genoprettes efter en skade ?

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 7 Den regionale specialisering af hjernen – funktionel lokalisation

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 8 FULD FUNKTIONEL GENOPRETNING TRODS KOMPLET SKADE AF HJERNESTRUKTURER (ALLOCENTRISK PLACE LEARNING) Mogensen et al. Brain Research Bulletin, 2004

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 9 ELLER GENOPRETNING? LOKALISATION ELLER? …

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 10 Hvordan er hjernen opbygget? MEN FØRST: Hvad består den af?

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 11 Netværk

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 12

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 13

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 14

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 15

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 16 Netværk - med nye medlemmer

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 17 NEUROGENESE I DEN VOKSNE HJERNE

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 18 Hvad sker der med de nye celler?

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 19 MEKANISMER for NEURONDØD

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 20 BDNF (Brain-Derived Neurotrophic Factor) samt andre trofiske faktorer …

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 21 TROFISKE FAKTORER

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 22 SPROUTING

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 23 MEKANISMER for NEURONDØD

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 24 ER DISSE NETVÆRK SÅ STATISKE ELLER PLASTISKE?

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 25 Ændres synapserne ved brug ?

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 26

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 27

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 28

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 29

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 30 ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET i dyremodeller

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 31 EXPERIENCE- ASSOCIATED SYNAPTIC PLASTICITY in animal models

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 32

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 33 ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET hos mennesker

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 34

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 35 ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET hos mennesker

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 36

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 37 ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET hos mennesker

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 38

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 39

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 40 ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET hos mennesker

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 41 HVAD PÅVIRKER HJERNENS PLASICITET? Stress?

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 42 HPA-Aksen

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 43

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 44

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 45 Faktorer, som påvirker HPA-Aksen

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 46 BDNF (Brain-Derived Neurotrophic Factor)

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 47 Atrofi p.g.a. Cortisol – BDNF´s Rolle

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 48 MEKANISMER for NEURONDØD

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 49 Cortisol ved depression

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 50 HPA-akse-aktivitet ved depression

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 51 Og hvad betyder det, når hjernen er ændret ?! - Der er ikke kun et muligt svar …

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 52

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 53 ”God” mor (mange ER) Opvækst ”Dårlig” mor (få ER) ”God” mor (mange ER) ”Dårlig” mor (få ER)

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 54 ”God” mor (mange ER) Opvækst ”Dårlig” mor (få ER) ”God” mor (mange ER) ”Dårlig” mor (få ER)

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 55 ”God” mor (mange ER) Opvækst ”Dårlig” mor (få ER) ”God” mor (mange ER) ”Dårlig” mor (få ER)

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 56 Ja - men … Epigenetik!

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 57

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 58

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 59

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 60

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 61 Faktorer med betydning for cortisol-receptorer i hippocampus og dermed HPA-akse-aktivitet – samt for depression 1.Genetik 2.Opvækst-betingelser 3.Akut stress

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 62 Virkninger af antidepressiva

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 63 BDNF og antidepressiva

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 64 Men tilbage til hjerneskade …

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 65 ELLER GENOPRETNING? LOKALISATION ELLER? …

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 66 FULD FUNKTIONEL GENOPRETNING TRODS KOMPLET SKADE AF HJERNESTRUKTURER (ALLOCENTRISK PLACE LEARNING) Mogensen et al. Brain Research Bulletin, 2004

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 67 Different Solution Strategies Mogensen, J., Lauritsen, K.T., Elvertorp, S., Hasman, A., Moustgaard, A. & Wörtwein, G. Place learning and object recognition by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex. Brain Research Bulletin, 2004, 63,

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 68 SHIFT in the NEURAL SUBSTRATE

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation MODIFICATION OF DEGREE OF CONTRIBUTION TO TASK MEDIATION BY INDIVIDUAL STRUCTURES: Some structures exhibit increased or decreased levels of contribution to task mediation 2. TASK-DEPENDENT AND DISSIMILAR NEURAL SUBSTRATES: After a given lesion the functional recovery of various cognitive tasks is mediated by unique and dissimilar neural substrates 3. APPLICATION OF NEW COGNITIVE STRATEGIES: The fully posttraumatically recovered individuals solve the task by applying new strategies that are dissimilar to those applied pretraumatically PHENOMENA OF POSTTRAUMATIC RECOVERY

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 70 ALGORITHMIC STRATEGIES ELEMENTARY FUNCTIONS NEURAL SUBSTRATES BEHAVIOUR X UNDERLYING COGNITIVE MECHANISMS AS A AS C EF 1 EF 2 EF 3 EF 4 EF 5 EF 6 EF 7 EF 8 EF 9 EF 10 EF 1 1 EF 12 EF 13 EF 14 EF 15 I II III IVV VI VII VIII IX X XI XII XIII XIV XV Brain structure α Brain structure β Brain structure γ UNDERLYING NEURAL MECHANISMS

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 71

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 72 ALGORITHMIC STRATEGIES (ASs) ELEMENTARY FUNCTIONS (EFs) NEURAL SUBSTRATES SURFACE PHENOMENA UNDERLYING COGNITIVE MECHANISMS UNDERLYING NEURAL MECHANISMS Mental/ Behavioural Manifestation level Final products in terms of mental states (potentially conscious) and overt behaviour Realized by a multitude of individual algorithmic strategies Mostly a result of experience and learning Consists of numerous elementary functions Truly localized If completely lost cannot be recreated Perform basic information-processing

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 73 ALGORITHMIC STRATEGIES ELEMENTARY FUNCTIONS NEURAL SUBSTRATES BEHAVIOUR X UNDERLYING COGNITIVE MECHANISMS AS A AS C EF 1 EF 2 EF 3 EF 4 EF 5 EF 6 EF 7 EF 8 EF 9 EF 10 EF 1 1 EF 12 EF 13 EF 14 EF 15 I II III IVV VI VII VIII IX X XI XII XIII XIV XV Brain structure α Brain structure β Brain structure γ UNDERLYING NEURAL MECHANISMS

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 74

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 75

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 76

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 77

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 78

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 79 Fra den skadede til den normale hjerne

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 80 REF - modularity within connectionist networks

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 81 ALGORITHMIC STRATEGIES ELEMENTARY FUNCTIONS NEURAL SUBSTRATES BEHAVIOUR X UNDERLYING COGNITIVE MECHANISMS AS A AS C EF 1 EF 2 EF 3 EF 4 EF 5 EF 6 EF 7 EF 8 EF 9 EF 10 EF 1 1 EF 12 EF 13 EF 14 EF 15 I II III IVV VI VII VIII IX X XI XII XIII XIV XV Brain structure α Brain structure β Brain structure γ UNDERLYING NEURAL MECHANISMS

UCN - The Unit for Cognitive Neuroscience ReCBIR – Research Centre for Brain Injury Rehabilitation 82 SÅ ER JERES HJERNER ÆNDRET … TAK FOR I DAG!