Jesper Mogensen, Professor
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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)
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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.
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Fra FORTVIVLELSE
- til HÅB
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BEHANDLING af og STØTTE til
patienterne:- større og bedre
indsats nu - OG en forskning,
som lægger grunden for fremtidens
behandling
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Hvad står i vejen for den bedre fremtid ?
- dårlig økonomi
- ”politisk” modstand (ledende
til økonomiske hindringer)
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Er rehabilitering efter hjerneskade
”uvidenskabelig” ?
- nej
- men hvordan kan hjernens funktioner både være ”lokaliserede” og genoprettes efter en skade ?
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Den regionale specialisering af hjernen – funktionel lokalisation
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FULD FUNKTIONEL GENOPRETNING
TRODS KOMPLET SKADE AF
HJERNESTRUKTURER
(ALLOCENTRISK PLACE LEARNING)
Mogensen et al. Brain Research Bulletin, 2004
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ELLER
GENOPRETNING?
LOKALISATION
ELLER? …
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Hvordan er hjernen opbygget?
MEN FØRST:
Hvad består den af?
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Netværk
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Netværk - med nye medlemmer
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NEUROGENESE I DEN VOKSNE HJERNE
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Hvad sker der med de nye celler?
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MEKANISMER for NEURONDØD
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BDNF (Brain-Derived Neurotrophic Factor) samt andre trofiske faktorer …
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TROFISKE FAKTORER
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SPROUTING
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MEKANISMER for NEURONDØD
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ER DISSE NETVÆRK SÅ STATISKE ELLER PLASTISKE?
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Ændres synapserne ved brug ?
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
i dyremodeller
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EXPERIENCE-ASSOCIATED
SYNAPTIC PLASTICITYin animal models
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
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ERFARINGS-ASSOCIERET SYNAPTISK PLASTICITET
hos mennesker
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HVAD PÅVIRKER HJERNENS PLASICITET?
Stress?
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HPA-Aksen
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Faktorer, som påvirker HPA-Aksen
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BDNF (Brain-Derived Neurotrophic Factor)
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Atrofi p.g.a. Cortisol – BDNF´s Rolle
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MEKANISMER for NEURONDØD
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Cortisol ved depression
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HPA-akse-aktivitet ved depression
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Og hvad betyder det, når hjernen
er ændret ?!
- Der er ikke kun et muligt svar …
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”God” mor(mange ER)
Opvækst
”Dårlig” mor(få ER)
”God” mor(mange ER)
”Dårlig” mor(få ER)
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”God” mor(mange ER)
Opvækst
”Dårlig” mor(få ER)
”God” mor(mange ER)
”Dårlig” mor(få ER)
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”God” mor(mange ER)
Opvækst
”Dårlig” mor(få ER)
”God” mor(mange ER)
”Dårlig” mor(få ER)
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Ja - men …
Epigenetik!
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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
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Virkninger af antidepressiva
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BDNF og antidepressiva
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Men tilbage til hjerneskade …
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ELLER
GENOPRETNING?
LOKALISATION
ELLER? …
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FULD FUNKTIONEL GENOPRETNING
TRODS KOMPLET SKADE AF
HJERNESTRUKTURER
(ALLOCENTRISK PLACE LEARNING)
Mogensen et al. Brain Research Bulletin, 2004
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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
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SHIFT in the NEURAL
SUBSTRATE
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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
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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
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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
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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
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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
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Fra den skadede til den normale hjerne
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REF - modularity within connectionist networks
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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
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SÅ ER JERES HJERNER
ÆNDRET …
TAK FOR I DAG!