1.2 Cardiovascular function Review-combined.pdf

Neuroplas*city:  An  Overview   History,  Mechanisms,  Applica*ons,  Rehabilita*on     Tushar  Issar   Ins*tute  of  Neurological  Sciences,   Prince  of  Wales  Hospital   [email protected]   The  Brain   • Composed  of  neurons  (~85  billio...

Neuroplas*city:  An  Overview   History,  Mechanisms,  Applica*ons,  Rehabilita*on     Tushar  Issar   Ins*tute  of  Neurological  Sciences,   Prince  of  Wales  Hospital   [email protected]   The  Brain   • Composed  of  neurons  (~85  billion)  and  glia  (~85   billion)   • Average  neuron  makes  ~10,000  synapses     – Synapses  can  be  excitatory  (glutamate)  or  inhibitory   (GABA)   • Neurons  are  specialised  for  controlling  motor   output,  sensory  processing,  or  connec*ng  regions     • Neurons  form  networks  that  are     responsible  for  specific  func*ons     Associate  Professor  Janet  Taylor   “Localisa*onism”   Pearson  Educa8on   History  of  Neuroplas*city   A  few  of  the  pivotal  studies  before  neuroplas4city  became  mainstream   • 1793  –  anatomist  Michele  Malacarne  discovered  animals  that   received  motor  training  had  larger  cerebellums  than  untrained   animals   • 1890  –  psychologist  William  James  proposed  the  brain  and  its   func*on  are  not  fixed   • 1945  –  neuroscien*st  Justo  Gonzalo  observed  dynamic  and   adap*ve  proper*es  aXer  brain  injuries     • 1964  –  Marian  Diamond  produced  first  scien*fic  evidence  of   anatomical  brain  plas*city.  Rats  in  an  enriched  environment  had   thicker  cor*ces  compared  to  rats  in  basic  environment.   History  of  Neuroplas*city   • 1964  –  David  Hubel  and  Torsten  Wiesel  inves*gated  the  effect  of   long-­‐term  closure  of  one  eye  on  brain  ac*vity  in  corresponding   visual  region  for  that  eye.  Found  that  same  brain  region  started   processing  informa*on  from  the  open  eye  instead  of  shut  eye.     • 1984  –  Michael  Merzenich  mapped  five  dis*nct  areas  in  sensory   cortex  corresponding  to  digits  1,2,3,4,5.  Digit  3  was  removed.  2   months  later,  s*mula*on  of  digit  2  or  4  evoked  ac*vity  in  cor*cal   region  where  digit  3  mapped  (adjacent  digits  invaded  unused   region)     • 1997  –  Eleanor  Maguire  documented  changes  in  hippocampal   structure  in  associa*on  with  acquiring  knowledge  of  London’s  road   layout  in  taxi  drivers.  Compared  to  controls,  size  of  hippocampus   was  same  but  posterior  hippocampus  was  bigger   Defini*on  of  Neuroplas*city   The  ability  of  the  nervous  system  to  respond  to   intrinsic  and  extrinsic  s*muli  by  reorganising  its   structure,  func*on,  and  connec*ons.     • Can  occur  at  molecular,  cellular,  system,  behavioural  level   • Can  occur  during  development,  in  response  to  the   environment,  during  disease,     or  aXer  therapy     – Developing  brain     exhibits  a  higher  degree     of  plas*city.       Kral  et  al.  (2010)   Mechanisms  of  Neuroplas*city   Change  in  one  neuron  (molecular  changes)   For  example,   -­‐ Change  in  receptor  conforma*on   -­‐ Altered  gene  expression   Associate  Professor  Janet  Taylor   Mechanisms  of  Neuroplas*city   Change  between  two  neurons  (cellular  changes)   For  example,   -­‐ Altered  synapses   -­‐ Larger  dendri*c  tree   Associate  Professor  Janet  Taylor   Mechanisms  of  Neuroplas*city   Change  in  a  network  of  neurons  (physiological,  anatomical,   behavioural  changes)   For  example,   -­‐ Different  cor*cal   map   -­‐ Improved  motor   performance   Associate  Professor  Janet  Taylor   Mechanisms  of  Neuroplas*city   Neuroplas4city  is  ac4vity-­‐  dependent   “Neurons  that  fire  together,  wire  together”   Long-­‐term  poten8a8on   -­‐ -­‐ -­‐ Long-­‐term  depression   Strong  depolarisa*on     in  post-­‐synap*c  neuron   results  In  high  influx  of   Ca2+   Triggers  inser*on  of   AMPA  receptors   Stronger  synapse   -­‐ -­‐ -­‐ Weak  depolarisa*on   Low  influx  of  Ca2+     results  removal    of  AMPA  receptors   Synapse  gets  weaker   Associate  Professor  Janet  Taylor   Mechanisms  of  Neuroplas*city   Neuroplas4city  in  development   Most  of  brain  growth  aXer  birth  is  in  cerebral  cortex   Growth  is  mainly  from  prolifera*on  and  elabora*on  of  axons  and   processes   • Cri*cal  period  -­‐  In  early  years,  we  develop  more  neurons  than  we  need.   Synapses  are  gradually  eliminated  in  ac*vity-­‐dependent  manner.     • Neurogenesis  s*ll  occurs  in  hippocampus,  olfactory  bulb,  and  cerebellum   in  adults.  Unknown  if  and  how  new  neurons  integrate  into  established   circuits.  Degree  of  neuroplas*city  in  adults  is  unknown.   • • S8les  &  Jernigan  (2010)   Applica*ons  of  Neuroplas*city   Example  1  –  Cerebellar  agenesis   Applica*ons  of  Neuroplas*city   Example  2  –  Neurotrophins  and  Stroke             BDNF  is  a  neurotrophic  factor  involved  in  neuronal  prolifera*on,  survival,   synap*c  plas*city,  learning  and  memory.   • BDNF  is  increased  in  cortex  during  motor     learning   • In  this  study,  BDNF  was  blocked  aXer  a     focal  ischaemia.  Received  rehab.   • BDNF  likely  has  a  role  in  motor  map    reorganisa*on,  learning,  and     memory  aXer  stroke.     • Applica*ons  of  Neuroplas*city   Example  3  –  Hemispherectomy   In  some  cases  of  severe     epilepsy,  one  hemisphere  of   the  brain  may  be  removed   or  disconnected.     • Extensive  reorganisa*on  may   occur,  such  that  the     remaining  side  is   responsible  for    motor    and  sensory  func*on  for     both  sides  of  the  body.     • Greatest  poten*al  is  seen     for  children  under  age  of  6.     • Applica*ons  of  Neuroplas*city   Example  4     Blinded  subject   Sighted  subject   Applica*ons  of  Neuroplas*city   Maladap4ve/Adverse  Examples   • Chronic  pain  following  limb  amputa*on  (phantom  limb)   – 80%  of  amputees  report  painful  feelings  from  areas  where  limbs  are   no  longer  present   – Previous  theory  was  that  nerve  endings   were  inflamed,  causing  pain  (disproved).   – In  1990s,  Vilayanur  Ramachandran     hypothesised  that  phantom  limbs  was  due  to   reorganisa*on  of  the  somatosensory  cortex.     • Stroking  face  resulted  in  percep*ons  of  phantom   limb  being  touched   – Other  theories  also  exist.  No  consensus.     cnx.org   Applica*ons  of  Neuroplas*city   Maladap4ve/Adverse  Examples   • Onset  of  epilepsy  aXer  cerebral  trauma   – Arises  months  or  years  aXer  insult   – Delayed  onset  suggests  progressive  changes  in  the  brain   • Axonal  sprou*ng  and  new  connec*ons  that  alter  signalling  and   induce  seizures   • Drug  Addic*on   – Transi*on  from  casual  -­‐>  compulsive  -­‐>  relapse  is     thought  to  be  caused  by  long-­‐las*ng    neuroadapata*ons  in  reward   pathways     – Reward  circuits  are  involuntary  ac*vated  and  execu*ve  func*on   circuits  are  hijacked  to  support  drug-­‐seeking  behavior.       Therapies  to  Promote  Neuroplas*city   • Brain  s*mula*on  (non-­‐invasive-­‐  or  invasive)   – Non-­‐invasive  –  transcranial  magne*c  s*mula*on  and   transcranial  direct  current  s*mula*on   – Invasive  –  deep  brain  s*mula*on   www.pyschscenehub.com       • Physical  training  and  exercise   www.medium.com • Cogni*ve  training   • Neuropharmalogical  interven*ons       Therapies  to  Promote  Neuroplas*city   Transcranial  Magne4c  S4mula4on     Nowak  et  al.  2009   TMS  is  used  to  ac4vate  lesion  side  and   suppress  inhibi4on  from  unaffected  side   Therapies  to  Promote  Neuroplas*city   Transcranial  Direct  Current  S4mula4on   www.neuromtl.com   Therapies  to  Promote  Neuroplas*city   Deep  Brain  S4mula4on   van  Hartevelt  et  al.  (2014)   Long-­‐term  DBS  can  affect   structural  and  func4onal   connec4vity   Therapies  to  Promote  Neuroplas*city   Physical  Training  and  Exercise   Sawaki  et  al.  (2008)   Constraint  therapy  for  upper  limb   has  been  associated  with  enlarged   motor  cortex  map   Therapies  to  Promote  Neuroplas*city   Neuropharmalogical  interven4ons     Asadollahi  et  al.  (2018)   Compared  with  placebo  groups,     pa4ents  on  citalopram  or  fluoxe4ne   had  significant  increases  in  Fugl-­‐Meyer   Motor  Scale   Future  Direc*ons  and  Clinical   Ques*ons   • Improved  means  to  assess  neuroplas*city  in  humans   • Op*mal  therapy  parameters  and  pa*ent  popula*on   • Biomarkers  for  predic*ng  and  monitoring  response  to   treatment     • Combina*on  therapies   – E.g.  Brain  s*mula*on  with  peripheral  nerve  s*mula*on   (neurons  that  fire  together,  wire  together)   – E.g.  physical  training  +  stem  cell  therapy   • Comprehensive  understanding  of  all  levels  of  plas*city   and  bener  animal  disease  models   • Bener  understanding  of  how  age  and  cri*cal  periods   influence  circuit  development   Neuroplas8city   Can  be  facilitated  in     disease  via  therapy   • TMS   • TDCS   • Exercise   • Pharmalogically   Occurs  within  and     between  neurons   Has  wide-­‐scale   applica8ons  in     disease  and  healthy     states   Depends  on   -­‐  Age  (youth)   -­‐  Environment   -­‐  Ac8vity     Will  occur  differently   for  each  individual   -­‐  Speed   -­‐  Possibili8es  of  change     Is  always  occurring   www.quantamagazine.org   Is  not  always  a     good  thing   Is  a  developing  field