Imaging and stimulating human brain plasticity

Transcription

1 Imaging and stimulating human brain plasticity Heidi Johansen-Berg! Nuffield Dept of Clinical Neurosciences, University of Oxford

2 Overview Structural plasticity: from micro to macro scale! Plasticity of body maps! Stimulating motor recovery after stroke

3 Overview Structural plasticity: from micro to macro scale! Plasticity of body maps! Stimulating motor recovery after stroke

4 the acquisition of new abilities requires many years of mental and physical practice. In order to fully understand this complicated phenomenon, it is necessary to admit, in addition to the strengthening of pre-established organic pathways, the establishment of new ones, through ramification and progressive growth of dendritic arborizations and nervous terminals. Ramon Y Cajal (1904)

5 Plasticity at a microstructural level before after Xu et al, Nature, 2009

6 Taxi drivers brains: does experience remodel the brain? Maguire et al, PNAS, 2000

7 Does white matter matter?

8 Does white matter matter? Membrane quality Myelin insulation Axon diameter Packing density Transmission speed Transmission quality Synchronisation of signals Behavioural responses

9 Assessing white matter with diffusion MRI Diffusion anisotropy quantifies the directional dependence of diffusion

10 Diffusion MRI is sensitive to relevant structural features of WM Membrane quality Myelin insulation Axon diameter Packing density Transmission speed Transmission quality Synchronisation of signals Behavioural responses

11 Variations in brain white matter relate to Johansen-Berg et al, Neuroimage, 2007 Bimanual(coordina-on(( 4" 3" 2" 1" variations in skill 0" 0.5" 0.55" 0.6" 0.65" 0.7" FA( grammar(learning(( 2.5" 2" 1.5" 1" 0.5" 0" 0.3" 0.4" 0.5" 0.6" FA( Floel et al, Neuroimage, 2009! For review see Johansen-Berg, Curr Op Neurol, 2010 TMS(func(connec-vity( Boorman et al, Curr Biol, 2007! 0.6" 0.4" 0.2" 0" +0.2" 0.1" 0.2" 0.3" 0.4" 0.5" +0.4" +0.6" FA(

12 Remodelling the brain with training Scan! 1 3 months Scan! 2 Draganski et al, Nature, 2004

13 Rewiring the brain with training Scan! 1 6 weeks Scan! 2 GM! increase WM! increase Scholz et al, Nature Neuroscience, 2009

14 Interpreting structural change? Grey matter plasticity White matter plasticity Diffusion change Grey matter increase Zatrorre, Fields & Johansen-Berg, Nature Neurosci, 2012

15 Relating MR change in grey matter to cellular change No correlation with NeuN or GFAP! Blumenfeld-Katzir et al, PLoS One, 2011! Lerch et al, Neuroimage, 2011!

16 What about white matter? Activitydependent changes in myelin? Blocking neuronal firing inhibits myelination! Stimulation enhances myelination! Demerens et al, PNAS, 1996! Ishibashi et al, Neuron, 2006!

17 Assessing changes in myelin with learning a) Accuracy SR Trained *! UR Control *! 72 rats in 3 groups:! Skilled reach (n=24)! Unskilled reach controls (n=24)! Caged controls (n=24)!! All animals had post-mortem diffusion MRI! Subset of 24 (n=8 per group) were processed for immunohistochemistry!! Days of training Sampaio-Baptista et al, J Neurosci, 2013

18 Learning-related increases in myelin WM anisotropy FA * a) Myelin MBP Optcal density stain SRT URT CC SRT URT CC Trained Control1 Control2 * c) Myelin MBP Optical stain density Contralateral M1 WM Learning rate Learning rate Sampaio-Baptista et al, J Neurosci, 2013

19 Interim Summary Experience shapes the structure of both grey and white matter! Neuroimaging can detect such changes though it is challenging to interpret them in biological terms! Animal studies allow for parallel imaging and histological measures to be taken and enable better interpretation of neuroimaging changes! Such studies suggest that activity dependent changes in myelin may contribute to white matter plasticity

20 Overview Structural plasticity: from micro to macro scale! Plasticity of body maps! Stimulating motor recovery after stroke

21 Plasticity in body maps: Detecting fine-grained cortical remapping with high-field fmri James Kolasinski

22 James Kolasinski

23 James Kolasinski

24 Assessing short-term plasticity in digit maps control A control B glued 1 week 24 hours 24 hours Control Glued n=12 (order counterbalanced across subjects) James Kolasinski

25 D2 D3 D4 D5

26 Remapping of digits after just 24 hours less overlap more overlap 26 James Kolasinski

27 Rethinking plasticity after amputation Tamar Makin

28 Tamar Makin Rethinking plasticity after amputation

29 Rethinking plasticity after amputation: patterns of compensatory limb use differ Intact hand Residual arm Residual arm missing hand cortex Relative intact hand use Residual arm use Residual arm Intact hand Intact hand n=11 n=18 n=11 n=18 Acquired amputees over-use intact hand, individuals with congenital limb absence over-use residual arm Makin et al, elife, 2013

30 The missing hand cortex represents the overused limb, whatever that limb is missing hand cortex Residual arm movements Intact hand movements hand cortex hand cortex Residual arm Intact hand Acquired amputees over-use intact hand, individuals with congenital limb absence over-use residual arm Makin et al, elife, 2013

31 Interim summary Short term! Change in sensorimotor experience alters digit representations! Long term! Individuals adapt to missing limb in different ways! Brain changes after amputation are not only due to sensory deprivation but also due to adaptive behaviour

32 Overview Structural plasticity: from micro to macro scale! Plasticity of body maps! Stimulating motor recovery after stroke

33 Brain stimulation to enhance plasticity? Transcranial direct current stimulation (tdcs) C A

34 Anodal stimulation of affected hemisphere speeds motor performance in chronic stroke patients Hummel et al, Brain, 2005! Sham stimulation provides a good placebo control

35 Are behavioural changes associated with changes in functional activity? % change in RT! 20! 15! 10! 5! 0! -5! -10! Task fmri! Behavioural improvements! * 20 mins 1mA anodal or sham tdcs to M1! % change in RT!! Correlations with behavioural gains! 10$ 0$!2$!1$ 0$!10$ 1$ 2$ 3$!20$!30$ fmri signal change Task fmri! Activity increases with stimulation! Correlations with behavioural gains! Stroke! side! -15! sham! anodal! Stagg et al, Brain, 2011!

36 Facilitatory brain stimulation to enhance learning or rehabilitation? Rehabilitative training, like learning, relies on brain plasticity! Anodal tdcs:! Facilitates plasticity and learning in healthy people! Reduces local GABA! Increases activity of stimulated M1! Speeds motor learning Stagg et al, J Neurosci, 2009, EJN 2009, Neuropsychologia 2009

37 Testing effects of repeated sessions of anodal tdcs + motor training Clinical measures and MRI 9 sessions of anodal tdcs + motor training Clinical measures and MRI Clinical measures Clinical measures Clinical measures and MRI Baseline 2 week therapy Post + 1 week + 1 month + 3 month Photos used with permission of participant and researchers n=24, chronic stroke patients Allman, Amadi et al, submitted

38 Repeated sessions boosts the clinical effects of motor rehabilitation after stroke Clinical measures and MRI 9 sessions of anodal tdcs + motor training Clinical measures and MRI Clinical measures Clinical measures Clinical measures and MRI Baseline 2 week therapy Post + 1 week + 1 month + 3 month UEFM ARAT WMFT Allman, Amadi et al, submitted

39 MRI shows that anodal tdcs increases recruitment and GM of stimulated motor cortex Clinical measures and MRI 9 days of anodal tdcs + motor training Clinical measures and MRI Clinical measures Clinical measures Clinical measures and MRI Baseline 2 week therapy Post + 1 week + 1 month + 3 month Grey matter fmri post vs pre, anodal vs placebo Allman, Amadi et al, submitted

40 Predicting treatment response from % change in RT with anodal tdcs! baseline measures? Ipsilesional M1 GABA! O Shea et al, Neuroimage, 2013!

41 Conclusions Experience shapes the structure and function of the human brain! Relating imaging changes to underlying biological events is challenging! Understanding plasticity can help design of new rehabilitation treatments

42 Acknowledgements FMRIB Plasticity Group:! Charlie Stagg, Jacinta O Shea, Tamar Makin, Adam Thomas, Claire Sexton, Andrea Dennis, Nancy Rawlings, Cassandra Sampaio, Antoin de Weijer, Jill Betts, Heather Neyedli, Christel Gudberg, YunYing Huang, Sanne Kikkert, Velicia Bachtiar, James Kolasinski Irene Tracey! Tim Behrens! Steve Smith! Mark Jenkinson! Karla Miller! Stuart Clare! Sean Foxley!!! Paul Matthews! Matthew Rushworth! Derick Wade! David Henderson Slater! Helen Dawes! Udo Kischka! David Bannerman! Niki Sibson!!