Post on 11-Dec-2015
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, ProfessorHead 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
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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 HospitalDepts. of Neurol. and Neurosurg.
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Fra FORTVIVLELSE
- til HÅB
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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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
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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
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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
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Den regionale specialisering af hjernen – funktionel lokalisation
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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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
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ELLER
GENOPRETNING?
LOKALISATION
ELLER? …
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Hvordan er hjernen opbygget?
MEN FØRST:
Hvad består den af?
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Netværk
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Netværk - med nye medlemmer
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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NEUROGENESE I DEN VOKSNE HJERNE
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Hvad sker der med de nye celler?
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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MEKANISMER for NEURONDØD
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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BDNF (Brain-Derived Neurotrophic Factor) samt andre trofiske faktorer …
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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TROFISKE FAKTORER
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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SPROUTING
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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MEKANISMER for NEURONDØD
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ER DISSE NETVÆRK SÅ STATISKE ELLER PLASTISKE?
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Ændres synapserne ved brug ?
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
i dyremodeller
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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EXPERIENCE-ASSOCIATED
SYNAPTIC PLASTICITYin animal models
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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HVAD PÅVIRKER HJERNENS PLASICITET?
Stress?
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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HPA-Aksen
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Faktorer, som påvirker HPA-Aksen
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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BDNF (Brain-Derived Neurotrophic Factor)
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Atrofi p.g.a. Cortisol – BDNF´s Rolle
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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MEKANISMER for NEURONDØD
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Cortisol ved depression
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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HPA-akse-aktivitet ved depression
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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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
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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”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
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”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
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”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
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Ja - men …
Epigenetik!
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Faktorer med betydning for cortisol-receptorer i hippocampus og dermed HPA-akse-aktivitet –
samt for depression
1. Genetik2. Opvækst-betingelser3. Akut stress
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Virkninger af antidepressiva
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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BDNF og antidepressiva
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Men tilbage til hjerneskade …
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ELLER
GENOPRETNING?
LOKALISATION
ELLER? …
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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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
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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, 217-236
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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SHIFT in the NEURAL
SUBSTRATE
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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1. 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 PHENOMENA OF POSTTRAUMATIC RECOVERYRECOVERY
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ALGORITHMIC STRATEGIES
ELEMENTARY FUNCTIONS
NEU
RAL
SU
BSTR
ATESBEHAVIOUR X
UNDERLYING COGNITIVE MECHANISMS
AS
A
AS
C
EF
1EF
2EF
3EF
4EF
5EF
6EF
7EF
8EF
9EF10
EF11
EF12
EF13
EF14
EF15
I
II
III
IV VVI
VII
VIII
IX
X
XI
XII
XIII
XIVXV
Brain structure α
Brain structure
β
Brain structure
γ
UN
DER
LYIN
G N
EUR
AL
MEC
HA
NIS
MS
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ALGORITHMIC STRATEGIES (ASs)
ELEMENTARY FUNCTIONS (EFs)
NEURAL SUBSTRATES
SURFACE P
HENOM
ENA
UNDERLYING COGNITIVE MECHANISMS
UN
DER
LYIN
G
NEU
RA
L M
ECH
AN
ISM
S
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
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ALGORITHMIC STRATEGIES
ELEMENTARY FUNCTIONS
NEU
RAL
SU
BSTR
ATESBEHAVIOUR X
UNDERLYING COGNITIVE MECHANISMS
AS
A
AS
C
EF
1EF
2EF
3EF
4EF
5EF
6EF
7EF
8EF
9EF10
EF11
EF12
EF13
EF14
EF15
I
II
III
IV VVI
VII
VIII
IX
X
XI
XII
XIII
XIVXV
Brain structure α
Brain structure
β
Brain structure
γ
UN
DER
LYIN
G N
EUR
AL
MEC
HA
NIS
MS
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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REF in POSTTRAUMATIC RECOVERY – and NORMAL PROBLEM SOLVING Level Observations of
posttraumatic recovery or problem solving by
Mechanisms of posttraumatic recovery or problem solving
Neuroplastic processes in posttraumatic recovery or problem solving
Mechanism instructing plastic changes
Surface phenomena
simple observation of behavior
proficiency of task performance
direct experience of mental/conscious content
Algorithmic Strategies (ASs)
detailed analysis of behaviour and cognition
Selection of AS Connectivity changes (synaptic modifications) within the selector/evaluator
Feedback to selector/evaluator regarding degree of behavioural success during evaluation of ASs
If alternative AS is not pre-existing: Creation of novel AS by REF
If alternative AS is not pre-existing: Changed connectivity (synaptic modifications) between EFs
Backpropagation on the basis of degree of behavioural success during evaluation of ASs
Elementary Functions (EFs)
None Changed participation in task solution
None
If alternative AS is not pre-existing: Changed input/output (connections with other EFs) – and changed participation in task solution
If alternative AS is not pre-existing: Changed connectivity (synaptic modifications) regarding input/output
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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Fra den skadede til den normale hjerne
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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REF - modularity within connectionist networks
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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ALGORITHMIC STRATEGIES
ELEMENTARY FUNCTIONS
NEU
RAL
SU
BSTR
ATESBEHAVIOUR X
UNDERLYING COGNITIVE MECHANISMS
AS
A
AS
C
EF
1EF
2EF
3EF
4EF
5EF
6EF
7EF
8EF
9EF10
EF11
EF12
EF13
EF14
EF15
I
II
III
IV VVI
VII
VIII
IX
X
XI
XII
XIII
XIVXV
Brain structure α
Brain structure
β
Brain structure
γ
UN
DER
LYIN
G N
EUR
AL
MEC
HA
NIS
MS
UCN - The Unit for Cognitive Neuroscience
ReCBIR – Research Centre for Brain Injury Rehabilitation
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SÅ ER JERES HJERNER
ÆNDRET …
TAK FOR I DAG!