Autism: Mirroring, Neurofeedback, and Empathy

Jaime A. Pineda, Ph.D. University of California, San Diego

U.S.A.

Outline of Talk

1.  Autism and the mirror neuron theory 2.  Mu rhythms and mirror neuron activity 3.  Empathy and mu rhythms 4.  Mu rhythm neurofeedback as neurological

rehabilitation in autism

Au#sm  Spectrum  Disorders  (ASD)  

  Problems  in:    Social  ability    Language  development    Behavior  

Common  Characteris#cs  of  Social  Dysfunc#ons  

–  Impairment  in  social  play  and  imagina#on  

–  Difficulty  interpre#ng  ac#ons  and  inten#ons  of  others  

–  Inability  to  par#cipate  in  a  reciprocal  conversa#on  

–  Language  delays  –  Impaired  joint/sustained  aEen#on  

–  Trouble  imita#ng  others  –  Absence  of  empathy    

Mirror  Neurons  

•  A  class  of  neurons  that  discharge  when  the  monkey  performs  an  ac#on  and  when  it  observes  a  similar  ac#on  done  by  another  agent  

–  Found  in:  •  area  F5  (homolog  of  Broca’s  area)  •  inferior  parietal  cortex  (PF/PFG/7b)  

–  Ac+vated  by:  •  Goal  directed  ac#ons          (reaching,  grasping,  holding)  •  Observa#on  of  similar  ac#ons  performed  by  “biological”  agents  

Di Pellegrino et al., Exp. Brain Res., 1992, 91, 176-80

Rizzolatti et al., Cogn. Brain Res., 1996, 3:131-141

Mirror  Neuron  Ac#vity    

 Perception-to-Action Mapping Selectivity

Action

Logically-Related (effector independent; 2X; Goal of movement)

Congruent (effector dependent; Kinematics of movement)

Perception

The  Mirror  Neuron  Theory  of  Au#sm  

–  Au#sm  as  deficits  in  imita#on    learning            (Rogers  and  Pennington,  1991)  – MNS  as  the  neural  basis  for  imita#on  learning            (Iacoboni  et  al.,  1999)  –  Dysfunc#ons  in  MNS  may  help  explain  social  dysfunc#ons  in  au#sm  (Williams  et  al.,  2001)  

       “  If  mirror  neurons  support  the  ability  to  imitate  others  and  to  understand  the  goal  behind  their  ac7ons,  the  disrup7on  of  this  system  might  also  impair  the  later  development  of  the  ability  to  understand  the  state  of  mind  of  other  individuals.”  

(Iacoboni and Dapretto, 2006; Meltzoff and Decety, 2003; Oberman and Ramachandran, 2007; Rizzolatti et al., 2009)

Dapretto et al., Nat Neurosci., 2006

Ac#va#on  for  Imita#on  of  Facial  Emo#ons  

Mu  Rhythms  and  Mirror  Neuron  Ac#vity    

•  Mu  rhythms  reflect  ac#vity  in  sensorimotor  cortex  that  is  modulated  by  MNS  (Altschuler  et  al.,  2000)  

•  Sensorimotor  simula#on  of  observed  ac#ons  are  reflected  in  mu  rhythm  ac#vity  (Pineda,  2005)  

Characteris#cs  of  the  Human  Mu  Rhythm    

•  Maximal  over  sensorimotor  areas  

•  AEenuated  or  blocked  by  movement  

•  Not  affected  by  opening/closing  the  eyes  

•  Not  affected  by  auditory/visual  s#mula#on  in  the  absence  of  movement  

Kuhlman, W.N., Electroenceph. Clin. Neurophys., 1978, 44: 83-93

The  Mirror  Neuron  System        

Iacoboni and Dapretto, Nature Reviews, 2006,7:942-951

mu  rhythm  (8-­‐12  Hz)  

MNS  Ac#vity  -­‐-­‐>  Suppression  

Normal  Oscilla#ons  at  rest  

Pineda et al., IEEE Trans. Rehab. Engr., 2000, 8(2): 219-222

Are  Mu  Rhythms  Affected  by  Ac#ons  and  the  Observa#on  of  Ac#ons?      

Baseline

Move

Observe

Imagine

Do  ASD  Children  Have  A  Dysfunc#onal  MNS?  

RATIONALE  

•  If  mu  rhythms  reflect  MNS  ac#vity  then  ASD  individuals  should  show  differences  in  mu  rhythms  compared  to  typically-­‐developing  controls  

Oberman et al., Brain Res Cogn Brain Res. 2005, 24(2):190-8.

Experimental  Paradigm  

•  Measured  mu  power  (2  min  of  EEG)  in  children  (7-­‐17  yrs):  –   Typically  developing  (n=12)  –   High  func#oning  ASD  (n=10)  

•  Condi#ons  –  Self-­‐movement  of  hand  

–  Watching  video  of  someone  moving  their  hand  

–  Watching  a  video  of  balls  moving  up  and  down  

ASD  Children  Exhibit  an  Absence  of  Mu  Suppression    to  Observa#on  of  Ac#ons  

Oberman et al., Neuropsychologia, 2008

 Is  the  Mirror  Broken  and  Unfixable?  

            RATIONALE  

           If  mirror  neurons  in  IFG  are  involved  in  the  direct  modula#on  of  sensorimotor  mu  rhythms,  then  temporary  inhibi#on  of  these  neurons  should  prevent  suppression  of  mu  rhythms  and  cause  “au#s#c-­‐like”  behaviors.  

Do  MNS  Areas  Modulate  Mu  Rhythms?  

Inferior parietal lobule

Superior temporal sulcus

Inferior frontal gyrus

Sensorimotor cortex

Keuken et al., Brain Research, 2011

 Measured  EEG  in  typically  developing  adults  (n=8)  before  and  aher  IFG  s#mula#on  

•  Observa#on  of  movement            (4  videos)  

– Simple  (hand  movements)  and  complex  (social  interac#ons)  

•  Baron-­‐Cohen’s  Eyes  Task    – Emo#on  and  gender  discrimina#on  

–  1  Hz  rTMS  (5  min  at  ~  40-­‐50%  absolute  threshold)  targeted  at  leh  IFG    

Method:    Transcranial  Magne#c  S#mula#on  

IFG  Inhibi#on  Results  in  an  Absence  of  Mu  Suppression  During  Observa#on  of  Ac#ons  

IFG  Inhibi#on  Reduces  Behavioral  Performance  in  an  Emo#on  Recogni#on  Task      

Reaction Time Accuracy

Empathy  and  Mu  Rhythms  

       Simula#on  theories  argue  that  during  the  processing  of  emo#onal  faces  observers  ac#vate  sensorimotor  representa#ons  involved  in  crea#ng  their  own  emo#onal  facial  expressions  in  order  to  recognize  the  emo#ons  and  infer  the  feelings  and  inten#ons  of  others  (Adolphs,  2003;  Goldman  and  Sripada,  2005).  

Do  mu  rhythms  reflect  sensorimotor  simula#on  of  facial  expressions  during  empathy?  

•  N=22  undergraduate  students  at  UCSD  (11  males/females)  

•  4  blocks  of  faces  (happy  and  disgusted)  in  two  condi#ons  (empathy/non-­‐empathy)  and  2  blocks  of  buildings  –  40  unique  photos  for  each  emo#on  (both  genders;  3  ethnici#es)  

presented  pseudorandomly  

–  Empathy:  “try  to  share  the  emo#ons  felt  and  expressed  by  the  photographed  people”    

–  Posi#ve  and  Nega#ve  Affect  Scale-­‐Expanded  (PANAS-­‐X)  filled  out  aher  each  empathy  condi#on  

–  Non-­‐empathy:  “rate  how  aErac#ve  the  photographed  face  is”  

Experimental  Paradigm:  Timing  of  Individual  Trials  

Methods  

•  32  channels  of  EEG  (linked  mastoid)  

•  Bandpass:    0.05-­‐30  Hz;  500  Hz  sampling  rate  •  Data  were  FIR  filtered  (4-­‐30  Hz)  •  A  three-­‐stage  second-­‐order  blind  iden#fica#on  (SOBI)  

algorithm  applied    –  Remove  EOG  components  

–  Remove  EMG  components  in  brain  ac#vity  

–  Iden#fy  mu  rhythm  components  

Leh  Hemisphere  Mu  Component  Clusters  

Right  Hemisphere  Mu  Component  Clusters  

Spectral  Analysis  

•  Event-­‐related  spectral  perturba#ons  computed  using  wavelet  decomposi#on  with  Morlet  tapers  

•  A  2  (empathy/non-­‐empathy)  x    2  (happy/disgusted)  repeated  measures  ANOVA    

ERD  present  at  500  ms  post  s#mulus  to  both  emo#ons  regardless  of  empathy    

ERSP  Results  

Neurofeedback  as  Neurological  Rehabilita#on  

•  Based  on  operant  condi#oning  (learning)  •  Noninvasive  •  Posi#ve  treatment  outcomes  obtained  rapidly  

•  Few  known  adverse  side  effects  •  Outcomes  maintained  long  aher  treatment  ends  

•  Principled  reason  or  theore#cal  underpinning  to  why  it  would  work  

Applica#on  of  EEG  Neurofeedback  

•  ADHD  •  Substance  abuse  •  Anxiety  •  Depression  •  Epilepsy  •  OCD  •  Learning  disabili#es  •  Migraines  •  Pain  •  Cogni#ve  impairments  •  Sleep  dysregula#on  

Neurofeedback  and  Au#sm  

Frontal  -­‐  parietal  areas  may  be  underconnected  

If  we  change  the  dynamics  of  the  sensorimotor  mu  oscilla#ons,  

And  these  oscilla#ons  are  func#onally  linked  to  the  MNS  network  (IFG,  IPL,  STS),  

Then  we  may  affect  func#onal  connec#vity  via  neuroplas#c  changes  and  recover  MNS  engagement  

This  can  lead  to  posi#ve  changes.  

IPL

STS

SM Cortex

IFG

User  

Interface  Technology  

Mul#channel  

Data  Acquisi#on  

Feature  Extrac#on  

PaEern  Recogni#on  

Mapping  to  Keyboard  Commands  

Applica#on  

BCI  System  

Mu  Rhythm-­‐based  Neurological  Rehabilita#on  

•  Amplitude  Training  at  C4  –  30  min  x  3/week  x  10/20  weeks  

–  HF  ASD:  7-­‐17  yr  olds,  n=27  

•  Experimental/Control  groups      –  Mu  ac#vity  above  threshold  (E)  

–  EMG  ac#vity  below  threshold    (E/C)    

Pineda et al., Research in ASD, 2008

Pre/Post  Assessments  

•  Verifica#on  of  diagnosis              (IQ,  ADI,  ADOS)  

•  Quan#ta#ve  EEG  •  Test  of  Variable  AEen#on  

(TOVA)  

•  Imita#on  ability  (Apraxia  imita#on)  

•  Mu  suppression  index  (MSI)  •  Au#sm  Treatment  Evalua#on  

Checklist    

•  Neuroimaging                                          (fMRI,  fcMRI,  DTI,  MRS)  

ASD  

TD  

TD  and  ASD  Groups  Learn  to  Control  Mu  Rhythms    

Global  Changes  in  Amplitude  and  Coherence  

ASD  Group  Shows  Recovery  of  Mu  Suppression  following  Training  

ASD  Group  Shows  Posi#ve  Changes  in  Sustained  AEen#on  

ASD  Groups  Shows  Posi#ve  Changes  in  Parental  Assessment    

Autism Treatment Evaluation Checklist

Conclusions

1.  Findings support the mirror neuron theory of autism

2.  EEG mu rhythms reflect mirror neuron activity 3.  Aspects of empathy can be measured by

changes in mu rhythms 4.  Neurofeedback centered on mu rhythms has

positive effects on symptoms of autism

•  Vilayanur  Ramachandran  •  Lindsay  Oberman  •  Eric  Altschuler  •  Andrey  Vankov  •  Bill  Skinner  •  Chulie  Ulloa  •  Brendan  Allison  •  Ed  Hubbard  •  Joe  McCleery  •  Erin  Hecht  •  David  Brang  •  ScoE  Carey  •  MaE  Schalles  •  Robin  Johnson  •  Julia  Stephen  

•  Adrienne  Moore  •  Rajiv  Rao  •  Chris  Robinson  •  Hanie  Elfenbein  •  Alex  Bressler  •  Steven  Thurman  •  Jena  Davis  •  Dong  Suk  •  Christa  Futagaki  •  Judith  Kaye  •  Lee  Edwards  •  Ralph-­‐Axel  Mueller  •  Brandon  Keehn  •  Alan  Lincoln  •  Dick  Gevirtz  

•  Oriana  Clark  •  Jia-­‐Min  Bai  •  Derrick  Asher  •  Dane  Chambers  •  MaE  Earhardt  •  Heather  Pelton  •  Alicia  Trigerio  •  Albert  Ayala  •  Stephen  Johnson  •  Steve  Gilmore  •  Nick  Pojman  •  Kelly  Head  •  Michael  Linden  •  Tom  Sullivan  

Collaborators