Amnesi. Clive Wearing Britisk musiker och körledare 1985 viral encefalit Normalt STM Inget LTM

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1 Amnesi Minnet Långtidsminne Korttidsminne/ arbetsminne Minne, lateralisering och språkstörningar Mikael Johansson Department of Psychology Lund University Clive Wearing Britisk musiker och körledare 1985 viral encefalit Normalt STM Inget LTM Diary: 8:31 AM: Now I am really, completely awake. 9:06 AM: Now I am perfectly, overwhelmingly awake. 9:34 AM: Now I am superlatively, actually awake. Deklarativt minne (Explicit minne) Semantiskt minne Fakta, generell kunskap, språk, t ex: Vad heter Frankrikes huvudstad? Vad kan man göra med en hammare? Är marvilan ett svenskt ord? Vad betyder H2O? Episodiskt minne Autobiografisk information om upplevda erfarenheter från en händelse bunden i tid och rum, t ex: Vad gjorde du igår kväll? Var parkerade du bilen i morse? Icke-deklarativt minne (Implicit minne) Procedurminne Färdigheter, t ex: Cykla Spela piano Perceptuellt minne Priming, underlättad bearbetning av sådant vi exponerats för tidigare, t ex: Identifikation Betingning Automatisk associativ inlärning, t ex Saliveringsreflex Minnets funktion Minnet Långtidsminne Korttidsminne/ arbetsminne Deklarativt minne (Explicit minne) Semantiskt minne Fakta, generell kunskap, språk, t ex: Vad heter Frankrikes huvudstad? Vad kan man göra med en hammare? Är marvilan ett svenskt ord? Vad betyder H2O? Episodiskt minne Autobiografisk information om upplevda erfarenheter från en händelse bunden i tid och rum, t ex: Vad gjorde du igår kväll? Var parkerade du bilen i morse? Icke-deklarativt minne (Implicit minne) Procedurminne Färdigheter, t ex: Cykla Spela piano Perceptuellt minne Priming, underlättad bearbetning av sådant vi exponerats för tidigare, t ex: Identifikation Betingning Automatisk associativ inlärning, t ex Saliveringsreflex Bartlett (1932) Minnet Deklarativt minne (Explicit minne) Semantiskt minne Fakta, generell kunskap, språk, t ex: Vad heter Frankrikes huvudstad? Vad kan man göra med en hammare? Är marvilan ett svenskt ord? Vad betyder H2O? Episodiskt minne Autobiografisk information om upplevda erfarenheter från en händelse bunden i tid och rum, t ex: Vad gjorde du igår kväll? Var parkerade du bilen i morse? Långtidsminne Korttidsminne/ arbetsminne Icke-deklarativt minne (Implicit minne) Procedurminne Färdigheter, t ex: Cykla Spela piano Perceptuellt minne Priming, underlättad bearbetning av sådant vi exponerats för tidigare, t ex: Identifikation Betingning Automatisk associativ inlärning, t ex Saliveringsreflex Grundläggande minneskomponenter Atkinson & Shiffrin (1968) Inkodning Lagring Framplockning The Modal Model Atkinson & Shiffrin (1968) Environmental input Sensory registers Visual Auditory Haptic Attention Short-term memory Temporary store Output Rehearsal Long-term memory Permanent store

2 Evidence for STM/LTM: serial position curve! Dissociations " logic some manipulations influence one section but not the other, suggests distinct sytems " primacy affected by! speed of presentation " recency eliminated by! delay! interference Seriepositionseffekter Korttidsminne Korttidsminne Kapacitet? Digit span George Miller (1956) The Magical Number Seven, Plus or Minus Two Kapacitet? Vad är ett item? Chunking 1939 R3 E1 V0 I6E1W9 S 83 osv sentences of about 15 words, compared to five or six unrelated words. Finally, our model had no mechanism Ericsson et al (1980) for allowing the phonological and visuospatial subsys SF digit span = 7 tems to interact, and offered no mechanism for the role of working memory in conscious awareness, which Following training (230 hours ) =to79 is assumed depend crucially on working memory. To account for these and other issues, a fourth Chunking based on running times component was proposed the episodic buffer. This is assumed to be a limited capacity store that binds together information to form integrated episodes. It is assumed to be attentionally controlled by the Left REVIEWS AR CE Working Memory The Modal Model Atkinson & Shiffrin (1968) Central executive Rehearsal Attention Environmental input Sensory registers Short-term memory Long-term memory Visual Auditory Haptic Temporary store Permanent store Output Visuospatial sketchpad Episodic buffer Phonological loop Visual semantics Episodic LTM Language Fluid systems Crystallized systems Baddeley (2000, 2003) Figure 5 The multi-component working memory revision. The dark purple areas represent long-term or crystallized knowledge. The episodic buffer provides an interface between the sub-systems of working memory and long-term memory (LTM). PFC: Delay-selective activity Working memory ho no u h o u on h n d r b n m r rom m mor h oth r p t nt ho th oppo t norm u tt nt on oup d th n t o th th m d h nd r b n n rom m mor pr um b r t n mp r d nn n o po tp r ptu m mor tor In on u on uo p t or n m mor n t but poor nt r t d r o r r h It ou d b n t r t rom mor nt r t on mon r rh ommun t t both m thodo o nd th or t nd rom n th th t n t r tur on u tt nt on n ud n or u n n -un t r ord n n non-hum n pr m t The central executive Stored vs. activated information Online processing Fuster (1989) h ntr ut th mo t mport nt but t und r tood ompon nt o or n m mor In th or n mod t mp tr t d poo o n r pro n p t to h h th omp u th t d d not m to b d r t or p r t d to th t o ub- t m r n d h rt tt mpt to d n th on pt m th th proto dopt th Norm n nd h mod o po tt nt on ontro h d d d ontro b t nt o pro h r t r d on th ontro o b h our sentences of about 15 words, compared to five or six unrelated words. Finally, our model had no mechanism for allowing the phonological and visuospatial subsystems to interact123, and offered no mechanism for the role of working memory in conscious awareness, which is assumed to depend crucially on working memory124. To account for these and other issues, a fourth component was proposed the episodic buffer125. This is assumed to be a limited capacity store that binds together information to form integrated episodes. It is assumed to be attentionally controlled by the PS executive and to be accessible to conscious awareness. Its multi-dimensional coding allows different systems to be integrated, and conscious awareness provides a AR convenient binding and retrieval process (FIG. 5). The buffer is therefore regarded as a crucial feature of VC the capacity of working memory to act as a global workspace that is accessed by conscious awareness along the lines suggested by Baars126,127 (neuropsychological support for such a system is reviewed by Dehaene and Naccache128). The buffer was presented as an entirely separate subsystem, but could be regarded as the storage component of the executive. This proposal differs from related proposals4,129 in assuming that long-term information is downloaded into a separate temporary store, Right rather than simply activated in LTM. It therefore emphasizes the capacity of working memory to manipulate and IS create new representations, rather than simply activating old memories. The concept of a common unified IS store has the further advantage of making the multice VC component model more compatible with approaches to working memory based on individual differences, which have emphasized executive processesisrather than subsystems such as the loop and sketchpad (BOX 1). Hjärnavbildningsdata REVIEWS p r r t on on om o on nd d tr t b t on oth r Left h d t n t on b t n utom t h b tu AR ontro nd tt nt on up r or ontro n PS CE mport nt on h h n o b n d to t n d n rom o p ho o r h nd o u ho d th t b h our n b d t rar m n d b h b t nd pr or tt tud o t n thout th VC r n o th ub t mp n ud un onanatomical localization of working memor y. Studies ou m t t on o bod po tur n on r t on based on lesion location in patients and neuroimaging in normal subjects indicate that the three basic compon u n o t on u h p do n b AR nents of working memory are localized in different nd n ronm nt mp t t t d t r ot p brain regions (FIG. 6). The case is most clear-cut for the phonological loop, for which lesion studies have indid t rm n t on o tr t ho cated the involvement of the left temporoparietal h on pt o n t n t nto r Right r hb region19,130,131. Subsequent neuroimaging studies have Figure 6 A tentative mapping of the working memory reinforced this conclusion, identifying BA 40 as the um t r nd o u on - ontro h h th Phonological model components onto the brain. The functions Central Visuospatial locusassociated of the storage component of are the loop, andtobroca s with each component not meant represent r u n b m ur d b mp qu t onn r th ISt area the (BA 6/44) as involved in the compoonly functions that are served by rehearsal the associated brain loop executive sketchpad regions, nor are these labels supposed to represent all brain. Vallar and Papagno review the neuropsynent pr d t r n o b h our rom r t n to p tt IS regions associated with a particular function. The central chological evidence for the anatomical localization of CE t mpt t on throu h d m p r orm n tovco executive (CE), for example, is likely to engage multiple 136 the phonological loop, while Smith and Jonidesbrain regions in a functionally coherent network, including review the neuroimaging evidence. A direct comparison h p t or nd mot on op n p t dorsolateral prefrontal cortex. AR, articulatory rehearsal;137 IS, IS of phonological and visuospatial working memory inner scribe (spatial rehearsal); PS, phonological store; VC, - ontro um d to m d t th t b d identified visuospatial as primarily visual cache (storage).working Modified, memory with permission, from REF. 29 localized in the right hemisphere, in agreement withwith (2001) Psychology Press. Anatomical image adapted, on t m th t m t d n p t nd ub t to 85,138,139 Appleton Lange. permission, from REF. 183 (1996). Other areas& that were earlier lesion studies h n b t n or n t u d n broadly analogous to the left hemisphere activation of verbal working memory, namely right inferior parietal pr nt ARn m mor nd ON I P HO O OCTOBER 2003 VOLUME 4 cortex (BA 40), right premotor cortex (BA 6) and right mport nt h n inferior frontal cortex (BA 47), were also involved, Working Memory although there was also activation in the anterior extrastriate occipital cortex (BA 19), which Kosslyn et al.140 Fractionating the executive. It ou d b r u d th t have suggested is associated with visual imagery137, A tentative mapping of the working memory Finally, neuroimaging studies are beginning to throw th tt mor th n homun u u th ttfigure m n model components onto the brain. The functions r light on the nature of rehearsal processes in p spatial t n th mport nt d on I ou d rassociated butwith each component are not meant to represent Central working memory, a topic that has proved difficult the only functions that are served by the associated brain d trto t executive r rd th homun u u o r n u u regions, nt nor are these labels supposed to represent all brain tackle using purely behavioural methods142. regions associated with a particular function. The central A number of studies have produced evidence for ah tr t pro d d pt th t th homun u u(ce), for example, is likely to engage multiple brain executive separation between spatial and visual or object coding, ontro in a functionally coherent network, including d n th prob m r but not th oregions ut on analogous to the what versus where distinction dorsolateral prefrontal cortex. AR, articulatory rehearsal; IS, mport in visual processing88,143,144. In general, neuroimaging h r qu r th t tt mpt r t to p inner scribe th (spatial rehearsal); PS, phonological store; VC, studies tend to support the claim that a dorsal stream visual cache (storage). Modified, with permission, from REF. 29 d n pro ttr but d to th homun u u nd th(2001) n Psychology to processes and storesphonological object information, with spatial Press.Visuospatial Anatomical image adapted, with Episodic Appleton & Lange. permission, from REF. 183 (1996) coding depending on the inferior sketchpad buffer loop parietal cortex87,145. u p n th m I b n b po tu t n th p t th t r n d d 4 b n tt nt on ontro 8r3 6n OCTOBER m to2003o VOLUME u to d d nd to t h tt nt on to th r th th n d to onn t or n m mor th M m d om pro r n o t n th p t to d d tt nt on ho t o t th t d m nd r d r nt p r ph r pro n n m ud tor d t p n nd uomotor tr n nd t tr t d th o d u t or h ub t to t nd rd o p r orm n th n t t d mu t n ou p r orm n ound th t p t nt th h m r d r r mp r d n ontr t to norm d r p op ho p t or d d n tt nt on not r b poor r th n or oun ub t executive and to be accessible to co Its multi-dimensional coding allow to be integrated, and conscious aw convenient binding and retrieval pro The buffer is therefore regarded a the capacity of working memory to space that is accessed by conscious lines suggested by Baars126,127 (neur port for such a system is reviewe Naccache128). The buffer was present arate subsystem, but could be rega component of the executive. This p related proposals4,129 in assuming th mation is downloaded into a separa rather than simply activated in LTM sizes the capacity of working memor create new representations, rather th old memories. The concept of a store has the further advantage of component model more compatib to working memory based on ind which have emphasized executive p subsystems such as the loop and sket Anatomical localization of workin based on lesion location in patients in normal subjects indicate that the nents of working memory are lo brain regions (FIG. 6). The case is m phonological loop, for which lesio cated the involvement of the le region19,130,131. Subsequent neuroim reinforced this conclusion, ident locus of the storage component of t area (BA 6/44) as involved in the nent Vallar and Papagno19 re chological evidence for the anatom the phonological loop, while Sm review the neuroimaging evidence. A of phonological and visuospatial w identified visuospatial working m localized in the right hemisphere, earlier lesion studies85,138,139. Oth broadly analogous to the left hemi verbal working memory, namely ri cortex (BA 40), right premotor cor inferior frontal cortex (BA 47), w although there was also activation i striate occipital cortex (BA 19), wh have suggested is associated with v Finally, neuroimaging studies are light on the nature of rehearsal p working memory, a topic that has tackle using purely behavioural meth A number of studies have prod separation between spatial and visu analogous to the what versus in visual processing88,143,144. In gen studies tend to support the claim t processes and stores object inform coding depending on the inferior pa r t on on om o o b t on oth r d t n t on b t n u nd tt nt on up r nt on h h n ob rom o p ho o ho d th t b h m n d b h b t nd pr or tt tud r n o th ub t mp ou m t t on o bod po tur n u n o t on u h p mp t t t d t r ot p Visual Episodic Language semantics LTM d t rm n t on o tr t ho h on pt o n t n t um t r nd o u on Fluid systems Crystallized systems r u n b m ur d b mp Baddeley (2000, 2003) pr d t r n o b h our rom Figure 5 The multi-component working memory t mpt t on throu h d m p r revision. The dark purple areas represent long-term or nd mot on op n p t crystallized knowledge. The episodic buffer provides an - ontro um d to m d t interface between the sub-systems of working memory and on t m th t m t d n p long-term memory (LTM).

3 Minnets neurala grund - Amnesi Minnesförlust till följd av hjärnskada, sjukdom eller psykologiskt trauma Henry Molaison (H.M.) 100,0 Memory performance 77,5 55,0 32,5 10,0 retrograde x anterograde Normal forgetting Amnesia patient past lesion present Milner & Scoville (1957) Mediala temporalloben (MTL) Project H.M Intact LTM Retrograde Anterograde Present Anterior Hippocampus Amygdala Perirhinal/entorhinal cortex Intakt icke-deklarativt minne Procedurellt minne Perceptual representation system Basal ganglia Cortical-subcortical loop Motor control functions Patient M.S. Normal declarative/explicit memory No perceptual priming!

4 Gravt försämrat deklarativt minne Vad gjorde du igår? Episodiskt minne Jacuzzi? Neocortical modules Visual Auditory Somatosensory Visuospatial Emotional Polymodal Medial temporal lobe (MTL) Intakt långtidsminne 1926 Retrograd amnesi 1942 Anterograd amnesi 1953 Hippocampus 2008 Squire & Zola-Morgan (1991) 342 Inkodning Perception vs framplockning feature binding Perception vs framplockning Visuell Study hippocampal index Framplockning retrieval cue -> partial reinstatement Test pattern completion -> full reinstatement Wheeler et al. (2000) PNAS Wheeler et al. (2000) PNAS Fig. 1. Schematic depiction of the proposed relationship between encoding- and retrieval-related processing in episodic memory. (A) Presentation of a stimulus event (a word superimposed on a scene) activates a diverse set of cortical regions. The resulting pattern of cortical activity is encoded by the hippocampus. (B) Following the event, a representation of the pattern of activity that it elicited is stored in the hippocampus. (C) Subsequent presentation of part of the event (the retrieval cue) leads to partial reinstatement of the original pattern of activity, which feeds forward to the hippocampus. (D) Overlap between the activity elicited by the cue and the stored pattern of activity causes the hippocampal representation to be re-activated, which in turn leads to full reinstatement at the cortical level. Retrograde Consolidation Spatialt minne Place cells Cortical modules Memory performance Deklarativt minne Relationellt till sin natur Control Amnesia 20 0 MTL Deklarativt minne Past Lesion Retrograde Present Anterograde Hippocampus Frankland & Bontempi (2005) Auditiv

5 MTL Deklarativt minne entation of (a) ventral and s of the brain. Shown are ocations of regions where object form, motion and ated motor patterns may be n from an increasing number e integrated in the temporal icity increasing along the or axis. Specific regions of polar region of the temporal olved differentially in ring, selecting and ntic information. MTL Deklarativt minne Maguire et al. (1998) Science Deklarativt minne Vad gjorde du igår? Semantic memory and the brain: structure and processes Martin and Chao 197 Semantiskt minne (a) Jacuzzi? Begreppsrepresentation Prefrontal cortex (b) Motor Selection Biological motion artifact Production Form Semantic working memory system Generic Unique e/ rgenc Conve tion ra integ Visual detail gure 1). This region is of particular interest association with the perception of biological nkeys [50] as well as humans [51,52]. for the ventral temporal cortex, neurons in mporal cortex may also be tuned to features ithin a category share. The nature of these known; however, on the basis of its anatomy to visual motion processing areas, this tuned to features of motion associated with cts. In support of this conjecture, increased terior lateral temporal cortex has been found s view static pictures of objects that imply 54] and when subjects focused attention on of eye gaze [55]. Investigation of the differproperties of motion associated with man-made objects may provide clues to the f this region. otor cortex and the representation of d motor movements associated with different object categories information about object properties, one tools to elicit activity in motor-related al laboratories have reported this association. reater activation of left ventral premotor n found for naming tools relative to naming,57] (see Figure 1), viewing pictures of tools h viewing pictures of animals, faces and nd generating action words to tools [58]. As of object form and object color, mental Current Opinion in Neurobiology Simons & Spiers (2003). Nat Rev Neurosci Martin & Chao (2001) when objects are grasped, but also when the animals view objects that they have previously manipulated [61]. The ventral premotor activation noted in the human neuroimaging studies may reflect a similar process. Alternatively, this activation may reflect action-planning [62]. Studies of patients with left premotor lesions will be needed to determine whether this region is necessary for naming and retrieving information about tools. Inkodning Framplockning Representation of the subordinate level and unique objects Donald Hebb ( The Organization of Behaviour, 1949) When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A s efficiency, as one of the cells firing B, is increased. Cells that fire together, wire together! A common characteristic of the studies described above was that object categories were represented by items named at the basic level (i.e. house, face, chair, dog, hammer) rather than at the subordinate or unique-object level (e.g. the White House, Marilyn Monroe, rocking chair, collie, sledgehammer). The most commonly studied category of unique entities has been famous faces. These investigations typically have observed activity in the anterior middle temporal gyrus [63,64,65] and temporal pole [63,66]. Evidence that activity in anterior temporal regions may extend to other classes of objects was reported by Gauthier et al. [67], who used picture word matching tasks on the basic and subordinate levels (although see [68]). These findings are consistent with Damasio s assersimons & Spiers (2003). Nat Rev Neurosci tion that the anterior regions of the temporal lobes are critical for retrieving information about unique entities [66,69]. Why this should be so is not clear. It can be assumed, however, that naming unique entities and making subordinate-level distinctions require access to more Minne på cellulär nivå A Simons & Spiers (2003). Nat Rev Neurosci B

6 (a) Hög frekvens Long-term potentiation (LTP) LTP (b) Låg frekvens Kräver högfrekvent stimulering Summering av postsynaptisk potential (depolarisering) Involverar NMDA receptorer N-methyl-D-aspartate Kalcium kanaler (Ca2+) Blockeras av magnesiumjoner (Mg2+) NMDA receptorer öppnas om LTP Long-term potentiation 1.Glutamat är bundet till receptorn 2.Postsynaptiskt membran är depolariserat Ca2+ inflöde PSP Post synaptic potential Inflödet av Ca2+ leder till intracellulära förändringar som påverkar synapsstyrkan Substanser som blockerar NMDA receptorer (tex. AP5) blockerar också uppkomsten av LTP LTD Long-term depression LTP LTP mekanismer AMPA Orsaker Nya AMPA receptorer Ökad receptorsensitivitet Ökad frisättning av glutamat 1. Kvävemonoxid (NO) Förändrad synaptisk struktur Presynaptisk Ökad frisättning av neurotransmittor 2. Postsynaptisk Ökat antal receptorer Ökad receptorsensitivitet Strukturella förändringar av dendrittaggar, antalet taggar, synapser 3. PET-bild av språkaktivering Språk Brocas område Wernickes område

7 Afasi Afasi Brocas område: språkproduktion motorisk (främre, expressiv) afasi Afasi - klassikerna Wernickes område: språkförståelse sensorisk (bakre, impressiv) afasi Wernicke Broca Tan Afasi Språkstörningar Överföringsafasi ( conduction aphasia ) Afasi - Dysfasi Alexi/agrafi Oförmåga att läsa/skriva Dyslexi Aprosodi Problem med spontant tal, repetition av tal, korrektion av språkfel Wernicke-Geschwind modellen Storhjärnan

8 Kontralateral projektion Corpus callosum Integrering nödvändig Konnektivitet Synkronisering via CC Commissurotomi Corpus callosum miljoner fiber (axon) WADA Amytal injektion Roger Sperry Nobelpriset 1981 WADA Amytal injektion

9 Språk Språk höger hemisfär Språk höger hemisfär Vänster hemisfär Broca (produktion) Wernicke (förståelse) Demonstration Begränsad slutledningförmåga Men, grundläggande språkliga funktioner även i höger hemisfär Grammatik vs. lexikon Språk höger hemisfär Data som tyder på att förmågan till språkproduktion kan utvecklas Visuospatial bearbetning Block design task (WAIS) Visuospatial bearbetning Igenkänning av (okända) ansikten höger hjärnhalva talade efter 13 år Lokal vs. Global Lokal vs. Global Lokal vänster hemisfär Global höger hemisfär

10 Teoretiska perspektiv Teoretiska perspektiv Teoretiska perspektiv Olika spatiala frekvenser? Matching vs. Maximizing Matching vänster Trycker T ~80% av fallen Neuron (visuella cortex) uppvisar känslighet för stimulusstorlek 75% 25% Slumpad ordningsföljd Människor matchar, råttor och guldfiskar maximerar Teoretiska perspektiv Teoretiska perspektiv Individuell variation Maximizing höger Trycker T ~100% av fallen Matching vs. Maximizing Sökande efter kausalitet -> tolkaren i vänster hemisfär Hänthet Vänsterhänthet ~10% av populationen Språkfunktioner Kontroll av tal i vänster hemisfär Högerhänta (95%), vänsterhänta (70%) Produktion vs. förståelse Inte lika tydlig asymmetri hos vänsterhänta Right-shift gene?, D (dextrality)/c (change) alleler 75% 25% Affektiv stil Vem är gladast? Funktionell asymmetri exempel & översikt Davidson Prefrontal asymmetri (EEG) Vänster! Positiv [Approach] Höger! Negativ [Withdraw] Vänster hemisfär Lingvistiskt material Lokal Höger hemisfär Komplexa former, spatiala relationer, ansikten Global Positive and Negative Affect Scale Språkljud Finmotoriska färdigheter Grammatik, fonetik Tolkande center (språk, matematik) Musik Rörelser i spatiala mönster Prosodi, emotionellt innehåll Spatial visualisering och analys Verbalt minne Icke-verbalt minne Fullt lexikon Begränsat lexikon

11 Funktionell asymmetri Varför specialisering? Naturligt urval Medför fördelaktiga egenskaper Extrahera kompletterande information från omgivningen Språk vs. fågelsång