Nervesystemets anatomi og funktion. Jens Bo Nielsen Tlf: Panum, 22.3

Transkript

1 Nervesystemets anatomi og funktion Jens Bo Nielsen Tlf: Panum, 22.3

2 Hvad I kan vente jer: Ikke systematisk pædagogisk gennemgang (kauserende?) Fysiologi ikke så meget anatomi Blandet engelsk-dansk Ikke muligt at komme ind på alt og meget bliver overfladisk Niveau? Ud af en tangent? Afbryd og stil spørgsmål

3 Generel forståelse af nervesystemet Udvikling af nervesystemet Motorik Neuroplasticitet

4 Hvad bruger vi hjernen til? Vægt: 1.5 Kg ca. 2 % legemsvægten Kognitive funktioner Motoriske funktioner Følesans nerveceller 750 ml/min = 15 % af blodvolumen i hvile Autonome funktioner Følelser Høresans Stillingssans Synssans synapser pr nervecelle Glukoseforbrug: 430 mmol/dag (75 g/dag) Samlet databehandling: Ca. 1x10 18 signaler pr s (bits/s)

5 Neuroarkæologi hjernens opbygning afspejler dens evolution Spinal cord Primitive motor synergies Hughlings Jackson

6 Første hominider Primater Pattedyr Vertebrater Første dyr med nervesystem Liv på jorden begynder

7 Seasquirt (Søpuppen) Et nervesystem, men kun når den har brug for at bevæge sig The sea squirt larva contains a primitive nervous system, which is used for controlling its movements. The adult sea squirt is stationary and has no nervous system

8 Det er kun hos pattedyr der ses en egentlig hjerne planlægning, udskydelse af umiddelbart behov, mental bearbejdelse af problemer, bevidsthed

9 Descartes and Willis and the concept of dualism: voluntary movement and reflexes Prochazka, Clarac, Loeb, Rothwell, Wolpaw What do reflex and voluntary mean? Modern views on an ancient debate Exp Brain Res 2000, 130(4):

10 Der er udtalt konvergens fra mange banesystemer på enkelte interneuroner

11 We should not talk of reflexes and voluntary movements as if it were two different things. Automatic spinal mechanisms contribute to all voluntary movements

12 The EMG activity is automatically adjusted to irregularities in the ground through sensory feedback af Klint, Grey, SInkjær, Nielsen J Physiol 2008

13 Sure you have sense, Else you could not move William Shakespeare, Hamlet 3. Akt, 4. scene De sensoriske og motoriske systemer er tæt integrerede med hinanden. Det er mere korrekt at tale om: et sensori-motorisk system F E Feedback from Skin Muscles Reflex gating Joints Phase-dependent gain j.b.nielsen@mfi.ku.dk

14 Den daglige maraton at leve uden sensorisk feedback

15 Betydningen af sensorisk input for motorisk funktion 1. Patienter med perifer polyneuropati 2. Motorisk funktion efter bedøvelse af fingrene At the age of 19 Ian Waterman was suddenly struck down at work by a rare neurological illness that deprived him of all sensation below the neck. He fell on the floor in a heap, unable to stand or control his limbs, having lost the sense of joint position and proprioception, of that "sixth sense" of his body in space, which we all take for granted. After months in a neurological ward he was judged incurable and condemned to a life of wheelchair dependence. j.b.nielsen@mfi.ku.dk

16 How many senses? 4 different receptors at least 2 different receptors 6. Balance 1. Touch 4 different receptors 2. Vision at least 2 different receptors 3. Hearing?? different receptors 7. Cold?? different receptors 8. Warmth 5 or more(?) different receptors 4. Smell?? different receptors 9. Position 4 (or 5) different receptors 5. Taste?? different receptors 10. Pain?? different receptors Do tendon organs (Ib afferents) contribute to perception? What is exertion? What is muscle fatigue? What is feels heavy? 11. Movement sense kinesthesia?

17 Sensory input is not only about perception

18 left_foot < < left_foot < < SPMmip [ e-016, , ] < SPM{T 138 } contrast(s) SPMmip [ e-016, , ] < SPM{T 138 } contrast(s) SPMresults:G:\fmri_sci\an_data\f4814 Height threshold T = {p<0.001 (unc.)} Extent threshold k = 0 voxels Design matrix SPMresults:G:\fmri_sci\an_data\f4814 Height threshold T = {p<0.05 (unc.)} Extent threshold k = 0 voxels Design matrix

19 Brain mapping what sense does it make? will we end up with Gall Phrenology all over again?

20 The multiwired brain What's really cool is that they've done fmri (functional magnetic resonance imaging) studies of musicians while they are improvising, like in jazz. Their entire brain lights up, with random connections going to before uncharted areas of brain real estate. Very Cool!!

21 Reorganization of visual areas in blind children

22 Vækst af neuroner (tidligt svangerskab) = 250,000 neuroner/minut Antal neuroner i hjernebarken er 20 milliarder ved fødslen (Biophysics of Computation. Information Processing in Single Neurons, New York: Oxford Univ. Press, 1999, page 87). Det totale antal synapser i hjernebarken er 240 trillioner (Biophysics of Computation. Information Processing in Single Neurons, New York: Oxford Univ. Press, 1999, page 87). Antal glia celler = antal neuroner 1 mio synapser dannes eller nedbrydes pr sekund livet igennem

23 Antal synapser fordobles i de første 5 år og falder derefter markant

24 Thalamus og hjernebarken viser det største fald i barndommen og ungdommen fjernelse af inaktive forbindelser, dannelse af mere rigide men stadig plastiske netværk Who is the most talented? Jernigan et al. 2005

25 Udviklingen af forbindelser fra hjernen til musklerne

26 Hjernens udvikling er selvfølgelig genetisk bestemt, men der er tæt interaktion mellem gener og omgivelser, så omgivelserne også får en stor betydning for hjernens udvikling (og ændring i udvikling ved fx CP). Specielt er udviklingen aktivitets-drevet; dvs. hvis der ikke etableres aktivitet i specifikke netværk på bestemte tidspunkter i udviklingen falder de væk A B C stop-kodon kodon for proteinerne et gen promotor kodon aminosyrer et gen protein

27 Mennesker har kun gener at gøre godt med hvilket slet ikke er nok til at forklare alle de celler og de funktioner der findes. Det drejer sig derfor ikke så meget om hvor mange gener vi har, men hvornår og hvor de bliver aflæst (hvilket er bestemt af omgivelserne) gener gener Det handler om gen ekspression!!

28 Figur 3 A. Hox-genernes styring af den rostro-caudale segmentelle udvikling. B og D. den dorsoventrale udviklingen styres af koncentrations-gradienter for BMP og SHH. C. nogle af de transkriptionsfaktorer der styrer udviklingen og specificeringen af motoriske og sensorsike neuroner SHH-gradienten i den ventrale (motoriske) delen af rygmarven A cervikal rygmarven B BMP thorakal rygmarven loftsplade lumbal rygmarven dorsalrodsgangliet D SHH gulvpladen nothocord hudafferenter specificers af Run 1 Trk A muskelafferenter specifcers af Run 3 Trk C motorneuronerne specificeres til de muskler de skal kontakte loftsplade di1 di2 - - di6 V0 V1 V2 motorneuroner gulvpladen

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39 Findes der tilsvarende kritiske perioder og hvilken betydning har de for motorisk funktion - hos mennesker? Hubel & Weisel, 1962, 1963, 1970

40 Mange forskellige områder i hjernen og rygmarven er involveret i kontrollen af gangbevægelser j.b.nielsen@mfi.ku.dk

41 Rygmarven hos katte kan frembringe gangbevægelser uden styring fra hjernen

42 Baby walking residual gait generator?

43 Rygmarvens gangcenter initieres af centre i hjernestammen j.b.nielsen@mfi.ku.dk

44 Men hjernen betyder da også noget

45 Kan man få børn til at gå tidligere hvis man træner dem? From Yang et al. 2002

46 Most children walk independently at the age of 1 year Development of gait The characteristic of human bipedal gait is the heel strike, eccentric contraction in TA, the weight-bearing on the lateral side of the foot and the push-off with the forefoot including the big toe. However, the adult (mature) gait pattern is not developed until age10-11 (step to step variability reduced, increased precision of movement, more economical muscle activity pattern.

47 Did Mozart have a special music gene Or was he only very motivated and hard working? The Symphony No. 1 in E flat major, KV. 16, was written in 1764 by Wolfgang Amadeus Mozart at the age of just eight years. This is usually taken as evidence of his extraordinary herited talent, but: 1. The symphony is not his best 2. He started practice at the age of 3 and practised 6 hours pr day. 5 x 6 x 365= hours of practice 3. He had a father who was acknowledged as the best music teacher at the time 4. He was highly motivated

48 Your brain changes continuously

49 Jeffrey Kleim et al. Exercise changes the brain in rats

50 -and in humans Size of MEP (% of Mmax) Test 1 Test 3 - after 5 weks of training Re-test - after 6 month without training 0,6 0,8 1,0 1,2 1,4 1,6 1,8 2,0 Intensity of stimulation (normalized to MEP threshold) (Lundbye et al. 2005)

51 No change in cortical representation of biceps muscle following strength training (Jensen JL, Marstrand PC, Nielsen JB. J Appl Physiol Oct;99(4): ) Size of MEP (% of Mmax) Test 1 Test 3 - after 5 weks of training 0,6 0,8 1,0 1,2 1,4 1,6 1,8 2,0 Intensity of stimulation (normalized to MEP threshold) Subjects trained biceps curls 3 times pr week in 4 weeks at 4-5 RM and 4 sets. 31 % increase of strength.

52 Cortical excitability changes are related to aquisition of task rather than performance Error (mm) Day of test after start of study Size of MEP Day of test after start of study Lundbye et al 2005, see also Pascual-Leone et al. 1999)

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54 Structural changes in the brain of children practising the piano Bengtsson et al. Nat Neurosci Sep;8(9):

55 Når motoriske færdigheder er indlært bibeholdes de oftest over meget lang tid men: Efter træning undergår indlæringen en periode med konsolidering, der er forudsætningen for praktisk motorisk retention. I denne periode er den motoriske hukommelse følsom for forstyrrelse ved træning af anden motorisk indlæring.

56 Virkningen af proteinsyntesehæmmer på hukommelse

57 Muellbacher et al. Nature 2002: M1 rtms can disrupt retention of a newly learned ballistic task

58 Hvad sker der, hvis man træner forskellige opgaver umiddelbart efter hinanden? Lundbye-Jensen, Petersen & Nielsen - in progress

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60 Exercise (maybe) improves math and language performance in school But high-quality controlled intervention studies are necessary

61 Exercise improves (cognitive?) learning in mice and rats Object recognition Morris water maze 8-arm maze Control Running O Callaghan et al Luo et al Van Praag et al Leggio et al Anderson et al. 2000

62 Mice doing treadmill running for 40 days have more new neurones in the hippocampus -and produce more BDNF Control Learner Swimmer Runner Enriched Van Praag et al. 1999

63 Some of the effects of exercise on the brain are mediated by Brain-Derived Neutrophic Factor (BDNF)

64 Exercise in combination with DHA (omega-3) boosts learning -at least in rodents + = Gomez-Pinilla 2008

65 Nutrition, exercise and mood disorders is there a link? Numerous studies have shown highly significant effect of exercise on depression (but it cannot be exluded that this is due to methodological bias more controlled, intervention studies required People with depression have lower levels of BDNF Antidepressants increase the level of BDNF

66 So in other words: + = Well, maybe... Please, send more money for research

67 Move It To Improve It Virtuelt web træningssystem Formålet med at anvende computerbaseret web-træning er at: 1. øge synergieffekten ved at træne opmærksomhed, hukommelse og motorik samtidigt. 2. motivere til hjemmetræning, der kan fungere sammen med de offentlige tilbud. 3. opnå en mere intensiv træning ved daglige rutiner og praksis.

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71 Read more in: which can be bought at:

72 Slut!!! Jens Bo Nielsen Panum

73 The ascending reticular activation system and arousal

74 Det limbiske system

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76 The limbic system is closely connected to the frontal cortex. - Emotional colouring of thought and behavior

77 Det ægte og det falske smil

78 NB: Laugther

79 Synsområderne i hjernebarken

80 En forenklet fremstilling af de centrale synsbaner (efter Crick)

81 Læsion i V5 medfører bevægelsesblindhed

82 diagnose? læsion i venstre V4

83 How do we put it all together?

84 Hjerneaktivitet når et objekt identificeres - og når det ikke gør

85 Der er koblet aktivitet i flere synsområder når et objekt identificeres, men ikke når det samme objekt ikke identificeres

86 Somatotopisk organisation i den primære sensoriske hjernebark

87 Plasticitet af den corticale repræsentation hos aber

88 Plasticitet af den corticale repræsentation

89 Højresidige parietallapsdefelter -konstruktionel forstyrrelse, og venstresidig visuel neglekt

90 Failure to recognize your own limb. Asomatognosia and Anosognosia The WADA test Meador et al. Neurology 2000, 55,

91 The rubber hand illusion

92 Premotor cortex coding of fake arm position rather than real arm position Graziano et al. Science 2000, 290,

93 Motor cortex neurones code extra-personal space as if it were part of self when using tools Maravita & Iriki TICS (2), 79-86

94 Firing properties of F5 neurones Rizzolatti G, Luppino G. The cortical motor system. Neuron Sep 27;31(6):

95 Mirror neurons. Rizzolatti G, Luppino G. The cortical motor system. Neuron Sep 27;31(6):

96 Styring af bevægelser vha implantater i den motoriske hjernebark Chapin, Ronald, Markowitz & Nicolelis Nature Neuroscience 1999, 2, j.b.nielsen@mfi.ku.dk Kennedy, Bakay, Moore, Adams & Goldwaithe IEEE Trans Rehabil Eng. 2000, 8,

97 Aktiviteten i den motoriske hjernebark kan bruges til at styre robotarme

98 Lillehjernen (cerebellum)

99 Forbindelser til cerebellum

100 Forbindelser fra cerebellum

101 Cerebellum har betydning for motorisk indlæring

102 Somatotopisk repræsentation i den primære motoriske hjernebark

103 Populationen af corticospinale nerveceller koder retningen af en bevægelse

104 Hjernens repræsentation af muskler er plastisk og ændres med træning / indlæring

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106 Time course of changes in the cortical representation of the biceps muscle in relation to motor learning (Lundbye, Marstrand og Nielsen, in Press) Size of MEP (% of Mmax) Test 1 Test 3 - after 5 weks of training Re-test - after 6 month without training 0,6 0,8 1,0 1,2 1,4 1,6 1,8 2,0 Intensity of stimulation (normalized to MEP threshold)

107 No change in cortical representation with passive movement or non-skill training erez et al Exp Brain Res Jul 28 [Epub ahead of print]