Disposition. Konnektivitet - nyckelfaktor Koppla funktion till hjärnans struktur

Transkript

1 Hjärnans nätverk Lars Nyberg Strålningsvetenskaper & Integrativ Medicinsk Biologi Umeå Universitet Disposition Nätverksperspektiv på kognitiva funktioner Nyckelroll frontalloberna: Perception Uppmärksamhet Semantiskt minne Arbetsminne Exekutiva funktioner Episodiskt minne: fronto-hippocampala samspel Pass 2 (efter lunch): Minnessystem - åldrande (fokus på episodminne) Koppla funktion till hjärnans struktur Kognitiv psykologi = studiet av hur hjärnan bearbetar information Kognitiv neuroanatomi vilka hjärnregioner är involverade? MRI NUS Foto: Elin Berge Kognitiv neuroanatomi Associationskortex och subkortikala regioner Konnektivitet - nyckelfaktor interaction among association areas leads to comprehension, cognition, and consciousness (Eric Kandel) Thalamo-cortical projections: Pulvinar -> parietal; medial dorsal nuclei -> frontal The thalamic input to association cortex has already been processed in primary areas Cortico-cortical connections: direct input from other cortical areas form majority of input to the association cortices. Ipsilateral as well as inter-hemispheric connections Cirka 80% av total cortical volym = associationscortex Förknippas med högre kognitiva funktioner (krav på integrering/association) Subcortical-cortical: from midbrain dopaminergic nuclei, noradrenergic and serotonergic nuclei in brainstem, cholinergic nuclei in brainstem and basal forebrain 1

2 Prefrontala kortex: Nyckelregion för högre kognitiva funktioner Vad-banan & Var/Hur-banan Perception & Emotion HOW Uppmärksamhet Inlärning & minne Exekutiva funktioner Perspektiv Mörker/dimma Kontext WHAT Liknande system för auditiv perception Emotionell perception Upplevd emotion - och dess reglering Det var ingen farlig spindel Thalamus Frontala-cortex Syn-cortex Amygdala Syninformation kan nå amygdala via; Thalamus snabbt Syncortex - långsamt Uppmärksamhet Selektiv Upprätthålla uppmärksamhet uppmärksamhet, skifta & styra vigilans, in uppmärksamhetsfokus vakenhetsgrad 2

3 Dela uppmärksamheten Uppmärksamhet hantera konflikt mellan automatiserade & kontrollerad processer Säg så snabbt du kan vilken färg orden är skrivna med RÖD BLÅ GRÖN SVART GUL GUL RÖD BLÅ Stroop: Responskonflikt mellan läsning och färgavkodning - måste inhibera visst svar Ökad aktivering av mediala PFC (främre gyrus cingulum) Fakta: Semantiskt minne En individs kunskapsbank: fakta, språk, begrepp mm mm Innehållet i semantiskt minne konceptuellt generaliserat och utan referens till viss händelse Vad är en Kettle bell? Frontala regioner kontrollerar aktivering av representationer i posteriora cortex Kettle bell förknippas med motorik/action och aktiverar bl.a. sensori-motoriska regioner Temporo-parietala konvergens-regioner integrerar information från modalitets-specifika regioner (visuella & action-representationer av kettle bell) => mer abstrakta / konceptuella representationer Arbetsminne System för att aktivt hålla information, och samtidigt utföra olika operationer på den (= manipulation) 12 x 11 Encoding Storage / maintenance (befintliga representationer; bidra skapa nya) Retrieval (delayed-match-to-sample etc) Hålla information i working memory DL Prefrontala cortex (Fuster) Hjärnavbildningsstudier: Fronto-parietal aktivitet Cabeza & Nyberg (2000) 3

4 Ökade arbetsminneskrav ökad hjärnaktivitet Uppdatering av arbetsminnet: Basala ganglierna & dopamin Många faktorer 5 påverkar 4 7 arbetsminneskrav: 1 3 Mängd information Uppgiftskrav (maintain Liten paus. vs. manipulate) Modell där basala ganglierna föreslås reglera uppdatering av arbetsminnet (O Reilly, 2006, Science McNab & Klingberg, NN, 2008) 5-veckors träning i att uppdatera arbetsminnet => ökad aktivitet i basala ganglierna Åldrande mindre dynamisk reglering (kan t.o.m. bli reduktion vid för höga krav) - Nyberg et al (2014) J. Cognitive Neuroscience Och påverkar dopamin (D2) systemet mätt med PET (Bäckman, Nyberg et al Science) Nedsatt WM/exektutiv förmåga Parkinsons sjukdom (Ekman et al, 2012, Lancet Neurol) Dahlin et al., 2008, Science Working Memory extensively studied: PubMed search 2014 => hits! (D Esposito & Postle, 2015, The Cognitive Neuroscience of Working Memory. Ann Rev Psychol., 66, ) Complex brain circuitry component processes Exekutiva förmågor Paraply-begrepp för många förmågor Planering Beslutsfattande Komplexa test Wisconsin card sorting Tower of London Nyberg & Eriksson (2015) in Learning & Memory by Mayford, Dudai & Kandel; Eriksson, Vogel, Lansner, Bergström & Nyberg (2015) Neuron Många delprocesser och hjärnregioner bidrar till prestationen på komplexa kognitiva test Frontoparietala exekutiva nätverk och dopamin -- ingredienser av arbetsminne & uppmärksamhet Uppmärksamhet Arbetsminne Miyake et al (2000) 4

5 Uppsummering: En frontal syntes Bensträckare Perception särskilt ur ovana perspektiv Emotion - reglering Uppmärksamhet vakenhet, selektion, inhibiering, dela Minne mer krävande framplockning / manipulering Exekutiva funktioner olika delprocesser Regional specialisering inom PFC Dorsolaterala PFC (& parietal-cortex) - nyckelregion för många funktioner - nätverk Semantic: Knowing cakes are served on birthdays PFC < > HC = kritisk för episodminnet Minnesprocesser Encoding Intentional - incidental Storage Gradual consolidation Retrieval Effortful - automatic Form memory traces of experiences Reactivate memory traces Hippocampus Simons & Spiers (2003) Nature Neurosci. Encoding retrieval interactions (transfer appropriate processing; encoding specificity) - context-dependent & state-dependent memory Available vs. Accessible in memory (Tulving & Pearlstone, 1966) - apparent forgetting may be an issue of not having effective retrieval cues Hippocampus & episodic encoding Why is hippocampus crucial for encoding? Patient HM: epilepy surgery 1953 Bilateral medial temporal lobe Removed anterior hippocampus & nearby cortex (entorhinal cortex) After surgery, HM not able to form new episodic memories (anterograde amnesia) Implicit forms of memory intact (chess) Old episodic memories spared (no retrograde amnesia) Indicated hippocampus crucial for creating episodic memories, but these not permanently stored in hippocampus Initial Storage Hippocampal System Novelty (Maas et al., 2014, Nature comm.) Pattern separation (car parked today vs yesterday) Binding of information Neocortical System 5

6 Top-down influences on encoding (intention and/or deep incidental processing) PFC support binding & add new information (associations) The role of self in episodic memory X Episodic memories not copies of past events - representations integrated with previous information Episodic memories always encoded in relation to I -1 st -person perspective (Tulving) Prefrontal cortex (PFC) engaged during encoding (Buckner, et al, 1999, Nature Neuroscienc - Often in left hemisphere (Tulving et al., 1994, PNAS; Nyberg et al., 1996, PBR; Salami et al., 2012, J Neurosci) Rashomon (Akira Kurosawa) - 4 persons memory of same event markedly different Clinical reports that dissociation of I can reduce episodic encoding (of traumatic events) - experience events from 3 rd -person perspective How test the role of I / 1 st -person perspective? => Collaborative project with Henrik Ehrsson and Loretxu Beugoignan at KI The nasty professor experiment Impaired episodic memory in out-ofbody condition Effect driven by not seeing face of actor? 4 separate episodes ( life events ) = evaluation of different areas of knowledge Experienced in-body or out-of-body Episodic memory tested after 1 week (semi-structured body-blind interview) R/K procedure Effect driven by out-of-body effect on hippocampus recruitment Storage Systems consolidation of encoded information Memories encoded out-of-body led to little hippocampus activation during early and intermediate retrieval trials -- no/weak auto/i-component in trace Anna Slow-changing connections Cortex 1 Cortex 2 Hippocampus binds the regions that together represent an event - fast-changing connections Gradual strengthening of connections among cortical regions (consolidation) - consolidation window (weeks +) - consolidated memories stable & not hippocampus-dependent (HM) - influenced by post-encoding events - e.g. rehearsal, repetition MTL Fast-changing connections 6

7 Revised consolidation model - encoding-retrieval interactions Memory retrieval: recognition She looks familiar Cortex 2 Stable, solid representations Re-activated representations - instable & possible to influence Recognition memory - not always taxing hippocampus proper (but MTL cortex) - can be based on familiarity (knowing rather than remembering) Memory retrieval: recall Incidental retrieval episodic recollection can be elicited in bottom-up manner => not frontal but hippocampus activation (Kompus et al., 2010, J Cog Neurosci.) Strategic (intentional) retrieval => (R.) prefrontal cortex (top-down) Nyberg, Cabeza & Tulving (1996) PBR What is her name? That is Anna Cortex 2 Cortex 1 Recollection > familiarity Eldridge et al (2000) Nature Neuroscience cf., Nyberg et al (1996) Nature Conscious recollection - hippocampus dependent - reactivation of other involved regions - remembering; autonoetic consciousness Hippocampus time-limited role in retrieval? Consolidation theory (Squire et al) * Hippocampus needed for initial storage and recovery of memory traces Hippocampal contribution diminishes over time as information becomes consolidated => neocortex eventually sufficient for storage & retrieval (cf., case HM) Multiple Trace Theory (MTT) * Hippocampus mediates autobiographical memory retrieval. * Each time an episodic memory is retrieved => re-encoding => formation of multiple traces (Moscovitch, Nadel et al., 2006, Curr Opinion Neurobiology) * Predicts hippocampal activation also for remote memories -provided they are vivid and detailed Slow-changing connections Cortex 1 Cortex 2 MTL Fast-changing connections Alvarez & Squire, 1994, (PNAS) Summary: episodic memory Encoding Lay down new long-term memories -- hippocampus (interactions with PFC & perceptual regions) - Requires a 1 st -person perspective (relation body-world) Storage Establish connections among distributed cortical regions -=> consolidated (resistant) - HC diminished role over time Retrieval Retrieve / re-experience past experiences -- intentional retrieval top-down => PFC -- successful retrieval => hippocampus & reactivate perceptual areas -- automatic retrieval => posterior route Reactivation can put consolidated memories into active state /re-consolidation (WM?) -- makes it possible to influence/alter consolidated memories 7

8 Frågor? 8