Neuropsykologins historia och teori Jarl Risberg JR-Neuroutbildning Kurs Avancerad Neuropsykologi 11 april 2019 Edwin Smith-papyrusen ca 1600 f. Kr. Edwin Smith-papyrusen beskriver hur man behandlar skador på skallen och bröstkorgen. Texten är skriven med hieratisk skrift och innehåller 48 olika skadebeskrivningar där 27 avhandlar olika skallskador och 6 avhandlar olika ryggmärgsskador. Alla fall delas upp i prognoserna gynnsamma, ovissa och ogynnsamma och presenteras i saklig ordning med namn, undersökningsfynd, diagnos och behandling. Texten beskriver bland annat att förlamningar i ena kroppshalvan kan orsakas av hjärnskador på den motsatta sidan, ett fynd som återupptäcktes mer än 3 000 år senare. René Descartes 1596-1650 1
Paul Broca 1824-1880 Phineas Gage Carl Wernicke 1848-1905 2
Santiago Ramon y Cajal (1852-1934) och Camillo Golgi (1843-1926) delade Nobelpriset i medicin eller fysiologi 1906. Cajal utvecklade neuronteorin: Hjärnan består av otaliga nervceller som är individuellt fungerande och som inte står i direkt anatomisk kontakt med varandra. Varje neuron överför information till andra neuron via nervfibrer. Golgi stödde inte neuronteorin utan hävdade att nervsystemet är ett enda anatomiskt sammanhängande nätverk. Aleksander Luria 1902-1977 3
Luria s Theory of Higher Cortical Functions The higher psychological processes represent complex functional systems They are social in their genesis Mediated by language in their structure Conscious in their performance Definition of a Functional System Brain functioning is not localized in a specific area of cerebral tissue, but is distributed in a constellation of cooperating zones of the cerebral cortex and the sub-cortical structures Luria s Theory of Higher Cortical Functions There are three fundamental areas of the brain which necessarily participate in any, even the least complex, psychological activity, each of which exerts a special influence in the organization of psychological processes Donald Hebb (1904-85) The Organization of Behavior (1949) 4
Long-Term Potentiation (LTP) D.O. Hebb 1949 THE SYNAPTIC PLACTICITY AND MEMORY HYPOTHESIS Activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation, and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed. Morris et al. 2003 5
Funktion Vänster hemisfär Höger hemisfär Syn Bokstäver, ord, enkla bilder Komplexa mönster, ansikten Hypothetical interactions between networks when constructing a sentence Hörsel Språkljud Icke-språkliga ljud, musik Känsel - Avkänning av föremål Rörelser Viljemässiga rörelser Rörelser i rumsliga mönster Minne Språkligt minne Icke-språkligt minne Språk Tala, läsa, skriva och räkna Språkmelodi Rumsligt tänkande - Geometri, riktning, former Fuster J., 2003 Maps of structural brain connectivity from nineteenth century cerebral cartography and present day connectomics From regions to connections and networks: new bridges between brain and behavior (a) White matter association pathways by the Belgian anatomist Arthur Van Gehuchten. (b) A similar lateral view by the Austrian neurologist Heinrich Obersteiner. (c) An map of the brain's white matter connections represented as a network. Spheres mark cortical network nodes and lines represent their connections as mapped with diffusion imaging and tractography. The network is shown with nodes placed into their anatomical coordinates, preserving the spatial embedding of the network. (d) The same network as in (c), but with nodes placed by a widely used visualization algorithm that projects the network into two dimensions and places nodes such that densely connected regions are located nearby. Most highly connected parts of the brain, corresponding to portions of the cingulate and posterior parietal cortex, are placed in the center of the plot. Activation studies examine relations between localized changes in signal amplitude and specific behaviors. Connectivity based studies take into account how communication between distributed areas contributes to individual behaviors. Network modeling methods, emphasizing modularity and the role of network topology, enable the discovery of particular subsystems and how these subsystems relate to behavior. Multivariate statistical models aim to directly model the relationship between distributed connection patterns and combinations of cognitive-behavioral phenotypes. Mišić & Sporns: Current Opinion in Neurobiology, Volume 40, 2016, 1 7 The Default Mode Network (Vilonätverket) Parcellation and network community detection Buckner, R.L., Andrews-Hanna, J.R & Schacter, D.L. (2008). The brain s default network. Anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 1-38. (a) A boundary map derived from group-averaged (n = 160) resting-state functional connectivity. Red/yellow colors in edge density mark locations on the cortical surface where patterns of functional connections exhibit abrupt changes. Black/blue/purple colors correspond to boundaries between relatively homogeneous regions. (b) A network map of the cerebral cortex derived by clustering resting-state functional connectivity measured in a large number of participants (n = 1000) into seven network communities. These communities correspond to several well-studied resting-state or intrinsic connectivity networks. Sporns, 2015 6
Cajals avbildningar av gliaceller Det finns uppskattningsvis 140.000.000.000 gliaceller i hjärnan. De vanligaste gliacellerna är protoplasmiska astrocyter som kan ha upp en miljon utskott. Utskotten är i kontakt med och reglerar nervceller, synapser, blodkärl och angränsande astrocyter. Relationen mellan nervceller och gliaceller Gliaceller spelar en avgörande roll för hjärnans anläggning, funktion och nutrition Pessoa L., 2014 Philip G. Haydon, Cerebrum, 2016 Hypothetical illustration of the major cellular components comprising the neurovascular unit in the cerebral cortex. Astrocyternas komplexitet utmärker den mänskliga hjärnan Interlaminära astrocyter Protoplasmiska astrocyter Polariserade astrocyter Jessica A. Filosa, and Jennifer A. Iddings Am J Physiol Heart Circ Physiol 2013;305:H609-H619 Fibrillära astrocyter 2013 by American Physiological Society Oberheim et al. Trends in Neurosciences, Volume 29, Issue 10, 2006, 547-553 7
Människans protoplasmatiska astrocyter är större och mer komplexa än musens och apans Oberheim et al., 2012 Given a synaptic density of approximately 1100 million synapses per mm 3 in rodent cerebral cortex, each protoplasmic astrocyte domain can encompass something in the order of 100 000 synapses. In humans, the synaptic density is estimated to be 1397 million synapses per mm 3. Therefore a single human protoplasmic astrocyte is positioned to encompass something in the order of one million synapses. This species difference begs the question of whether human astrocytes have the potential to more powerfully modulate interneuronal signaling and potentially integrate information from multiple synapses in a manner increasing the computational power of the human brain. Oberheim Bush, N.A. & Nedergaard M., 2017 Laboratorieråtta får mänskliga astrocyter genom inympning Förbättrad inlärningsförmåga efter inympning av mänskliga astrocyter Han, X. et al., Cell Stem Cell, 2013 Han et al., 2013 Den intracellulära Calcium responsen kommer före den elektrofysiologiska aktiveringen i en musmodell A single astrocyte (pink) can ensheath tens of thousands of synapses; modulate synaptic transmission by the release (red arrow) and removal (blue arrow) of neurotransmitters and neuromodulatory substances and by controlling ion concentration and modulating blood flow locally. These results support a key role for gamma oscillations in recognition memory. Ca 2+ These data reveal an unexpected role for astrocytes as essential contributors to information processing and cognitive behavior. (30 80 Hz) som är av betydelse för Gammavågor vid förmågan att känna igenkänningsminne föremål. Mätning av Calcresponse Hosuk Sean Lee et al. PNAS 2014;111:32:E3343-E3352 R. Douglas Fields et al. Neuroscientist 2013;20:426-431 Copyright by SAGE Publications 8
Specific astrocytes for specific circuits. The tripartite synaps Aryn H. Gittis, and Daniel J. Brasier Science 2015;349:690-691 (a) Electron micrograph showing a presynaptic (Pre) and postsynaptic (Post) terminal enwrapped by the astrocytic process (green) forming the tripartite synapse. (b) The close association of the astrocytic process with the presynaptic and postsynaptic terminals exerts crucial roles in clearing K + ions that accumulate following neuronal activity, and in the uptake of the synaptic transmitter glutamate by the activity of plasma-membrane glutamate transporters. Additionally, neurotransmitter release from presynaptic terminals can activate astrocytic receptors that induce Ca2+ elevations which in turn triggers the release of gliotransmitters from these cells. Published by AAAS The Evolving View of Astrocytes, Philip G. Haydon, Cerebrum, October 2016 Bidirectional Neuron-astrocyte Communication Synaptic Modulatory Actions of Gliotransmitters (A) Schematic drawing of the tripartite synapse illustrating the location of low and high affinity ligand receptors. (B) Neurotransmitters rapidly activate low affinity receptors at the postsynaptic neuronal membrane and diffuse outside the synaptic cleft to activate high affinity receptors at the astrocytic membrane. (C) Gliotransmitters activate high affinity receptors at perisynaptic locations in the neuronal membrane. Neurotransmitter (B) or gliotransmitter (C) decreasing concentrations over distance from release sites is illustrated by different color intensity. Gliotransmitters Travel in Time and Space Alfonso Araque, 1,2 Giorgio Carmignoto, 3 Philip G. Haydon, 4 Stéphane H. R. Oliet, 5,6 Richard Robitaille, 7,8 and Andrea Volterra 9 Neuron Volume 81, Issue 4, 19 February 2014, Pages 728 739 Araque et al. Neuron 2014 Low levels of synaptic activity (blue arrow, left) evoke rapid, spatially restricted Ca2+ elevations at an astrocytic process (red trace) resulting in a gliotransmitter release that locally modulates synaptic transmission (green arrow, right). The change in synaptic efficacy due to gliotransmitter-mediated regulation of the probability of release is illustrated as an increase in the mean amplitude of excitatory postsynaptic events (dashed and solid blue line Ca2+ elevations evoked at an astrocytic process by an intense activity of an individual synapse diffuse to a nearby process (red arrow) to trigger gliotransmitter release that affects nearby synapses (right). The red superimposed traces are the integrated Ca2+ response (solid line) and the elementary Ca2+ response (dashed line). As a result of this astrocyte modulatory action, synaptic transmission (solid blue line) can be either potentiated or depressed, while the elements that are not the focus are greyed. Multiple Ca2+ events at different processes evoked by simultaneously active synapses are spatially and temporally integrated (left) resulting in a global, long lasting Ca2+ elevation that can affect synaptic transmission in the territory of individual astrocytes (right). The global Ca2+ response (solid line) and the integrated Ca2+ response (dashed line, same as solid line in B) are reported. Note the different time scale of Ca2+ traces in (A), (B) and (C). Layout of neuron cell bodies, dendritic network and axonal fibres (grey) transmitting action potentials (red arrows). Astrocyterna kommunicerar med varandra genom att skicka calcium-vågor via gap junctions (a) One dendrite of interest is designated by arrowheads. (b) The mosaic of astrocytic domains is superimposed to the background neuronal network. (c) Different contiguous segments of the same dendrite (arrowheads in a) intersect distinct astrocytic domains. Synapses are controlled independently within each of these domains (synaptic islands). (d) One astrocyte covers portions of different dendrites, belonging to four distinct neurons, surveying the activity of a total 20 000 160 000 synapses. Thomas Papouin et al. Phil. Trans. R. Soc. B 2017;372:20160154 Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity Alfredo Pereira Jr, Fábio Augusto Furlan Progress in Neurobiology, Volume 92, Issue 3, 2010, 405 420 9
Astrocytes and human cognition Modeling information integration and modulation of neuronal activity Astrocytes and human cognition Modeling information integration and modulation of neuronal activity A biophysical Global Workspace composed of a network of astrocytes. Blue stars represent protoplasmic astrocytes and red trees represent neurons. Each astrocyte participates in a tripartite synapse, being activated by the pre-synaptic neuron. Alfredo Pereira Jr, Fábio Augusto Furlan Progress in Neurobiology, Volume 92, Issue 3, 2010, 405 420 Consciousness as The Feeling (astroglial sentience) of What Happens (neuronal awareness). Awareness and sentience of information patterns can occur unconsciously, but when they occur together the informational content becomes conscious. Alfredo Pereira Jr, Fábio Augusto Furlan Progress in Neurobiology, Volume 92, Issue 3, 2010, 405 420 En modell för hur det astrocytiska nätverket fungerar som en överordnad kontrollenhet (Master Hub) för olika hjärnfunktioner Astrocyternas betydelse för hjärnans struktur och funktion Alfredo Pereira Jr, Fábio Augusto Furlan Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity Progress in Neurobiology, Volume 92, Issue 3, 2010, 405 420 1. Stödjande hjärnans lim 2. Reglerar jon- och vatten-homeostas, avfallshantering 3. Upprätthållande av blod-hjärnbarriären 4. Regleringen av hjärnans blodflöde 5. Bildandet av stamceller 6. Bildandet av synapser 7. Aktivt engagemang i synaptisk transmission 8. Avger neurotransmittorer av alla typer (glutamat, GABA m fl) 9. De ca 2 miljoner utskotten från en protoplasmatisk astrocyt påverkar nervceller, synapser och blodkärl inom ett avgränsat område (domän). 10.Domänerna kan snabbt överföra information mellan varandra, och utgör ett underlag för vakenhetsreglering, perception, minne och medvetande. Hoppas att era astrocyter inte är helt SLUT Tack för intresset! 10