jesper mogensen, professor

CHALLENGING THE CONCEPTS OF LOCALIZATION

AND RECOVERY OF BRAIN FUNCTION

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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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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hos mennesker



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hos mennesker



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hos mennesker



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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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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)





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Opvækst






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Opvækst






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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


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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NEU

RAL

SU

BSTR

ATESBEHAVIOUR X


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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NEU

RAL

SU

BSTR

ATESBEHAVIOUR X


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!

jesper mogensen, professor

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