1. NEURO FEEDBACK TO NEUROLOGY-
NEUROLOGIST’S PERSPECTIVES
Prof. A.V. SRINIVASAN, MD, DM, Ph.D, F.A.A.N, F.I.A.N,
EMERITUS PROFESSOR
TAMILNADU DR.M.G.R MEDICAL UNIVERSITY
CHENNAI
PRESIDENT SABA – INDIAN CHAPTER
11th November 2010

2. Einstein’s Brain
 1879-1955

3. Einstein’s Brain
 Einstein died in 1955 at age 76. His
brain was stored by Dr Thomas
Harvey, pathologist, who performed
the autopsy.
Harvey cut the brain into 240 pieces, which
he kept in jars at his house. Harvey moved
around the country but he always brought
the brain with him. He eventually sent parts
out to be studied to various researchers in
the 1980s and 1990s.
(Reference: Abraham, C., Possessing
Genius: The Bizarre Odyssey of Einstein's
Brain, New York: St. Martin's Press, 2002)

4. Einstein’s Brain: Smaller Size
 1879-1955

5. Einstein’s Brain: Parietal lobe
 Parietal lobes are responsible for visual
and 3-D representation and mathematical
reasoning.
 E’s inferior parietal lobules are not divided
by major cleft
• Not seen in 191 controls!
• Axons were connected in unusual ways
 “might have allowed for his brilliance and his ability
to put spatial representations into mathematical
concepts”

6. Einstein’s Brain: Hippocampus
 E’s left hippocampal neurons were
larger in 4 of 5 five regions
compared to right.
• Controls showed minimal and
inconsistent asymmetry.
• Larger neurons in left hippocampus, DW
Zaidel noted, imply that Einstein's left
brain may have had stronger nerve cell
connections between the hippocampus
and neocortex than his right.

7. Einstein’s Brain: Other Differences
 Total brain weight of only 1,230
grams (average same-aged male =
1,350 grams).
 Thickness of area 9 (prefrontal
cortex) was thinner than that of 5
controls, but same number of
neurons.
• Thus density of neurons in AE’s brain
greater.

8. "On the Brain of a Scientist: Albert Einstein”
Diamond, Scheibel, & Murphy (1985)
 Surveyed neurons and glia in left
and right area 9 (important in
planning) and area 39 (language
and integration)
• More glial cells per neuron in AE
compared to 11 age-matched male
controls.
• Left area 39 most significant difference
 Conclusion: AE’s neurons may
have had an increased
"metabolic need"

9. Is brain-behavior behavior?
 If so, it can be
conditioned just
like other
behaviors
 In 1960s, certain
rhythms could be
“trained”
 Led to
Neurotherapy and
Brain-Computer
interfaces (BCI)

10. Definition of Learning
 Learning is an adaptive1 permanent
change2 in behavior or behavior
potential3 that is produced as a result
of prior experience4
 1 occasionally maladaptive such as depressed mental set,
obsessions
 2 not due to fatigue, injury
 3 includes tendencies to respond that might not have been
tested
 4 excludes maturation, disease, instinct

11. Two forms of conditioning
 Classical conditioning
• Hard-wired linkage between stimulus and response
(e.g., food and saliva)
• Anything acting as signal of food can produce response
 Operant conditioning
• Training linkage between stimulus and response through
reinforcement
• behavior strengthened if followed by reinforcement
• behavior weakened if followed by punishment
• Law of Effect (Thorndike)
• Rewarded behavior is repeated

12. Components of conditioning
 Acquisition
• initial stage of
learning, during
which a response is
established and
gradually
strengthened
 Effective pairing of
reinforcement

13. Extinction
• diminishing a conditioned response
• occurs when an response is not followed by a
reward

14. Extinction and spontaneous recovery
Acquisition
Strong (response
+ reward) Spontaneous
Extinction recovery of
(no reward) response
Strength
of CR
Extinction
(no reward)
Weak
Pause
Time

15. Operant Conditioning
 Spontaneous recovery
• reappearance, after a rest period, of an
extinguished conditioned response
 Generalization
• tendency for stimuli similar to the
conditioned stimulus to evoke similar
responses
 Discrimination
• Identify specific stimulus from set of similar
stimuli to evoke similar reinforced responses

16. When you become aware of your own
brain activity –you can change it also.

17. Electrical stimulation of brains (ESB)
 Electrical stimulation of brains of rats
- James Olds in 1950s;
• Jacobsen and Torkildsen replicated
work in humans;
• some epileptics stimulated
themselves into convulsions


18. INTRA-CRANIAL SELF-
STIMULATION
 Rodent wireheads
• 0.0005 amps whenever rat pushed lever
• Up to 10,000 bar-presses an hour recorded
• Animals self-stimulate > 24 hrs continuously without
rest, and cross electrified grid to gain access to lever
• Reward center: Medial forebrain bundle passing through
lateral hypothalamus and ventral tegmentum
• Other brain centers are aversive, such as periaqueductal
grey matter (PAG)
• Ventral tegmental area (VTA) neurons manufacture
dopamine and they are under continuous inhibition by
gamma-aminobutyric acid (GABA) system, an important
component of the ”final common pathway" of reward,
implicated in addiction, mood, and learning.

19. Delgado, Primate wireheads, and
Circuitry man

20. Electrical stimulation of brains
(intracranial stimulation)
 Pavlov conditioning experiments
• Tone for food, buzzer for shock –
• Moved them closer together in time
• confounded dog fell asleep
 Termed “internal inhibition”
 Animal can close down own
systems to avoid stress

Neal E Miller trained autonomic functions
• Dogs salivate to get food
• Rats control heartrate to get water

21. History of Biofeedback
 JH Bair, 1901, instrument used to teach ear wiggling

In early 20th century, J.H. Schultz in Germany developed a
technique called Autogenic Training. Verbal instructions are
used to guide a person to a more relaxed and controlled
physiological state.
• The method flourished, and the results were reported upon by
Wolfgang Luthe in 1969 in the United States.
 Increased awareness in Western world of yogic ability to
alter physiology volitionally. E.g., a yogi could survive in a
sealed box by voluntarily reducing his metabolic rate
significantly, surviving hours with a limited supply of
oxygen.
 Peripheral biofeedback techniques include
• GSR, thermal, breathing, cardiac

22. History of EEG biofeedback
 1934, Adrian watched his EEG in front of
oscillograph and created alpha at will
 Alpha biofeedback or deep states
• Joe Kamiya at Univ of Chicago,
1958+
 Kamiya 1958
• 1st subject - 60 tones and 60
guesses, half right
• 2nd trial, 65 % correct
• 3rd 85% correct
• 4th, after a few mistakes, 400 correct
in a row
 1968 first congress in Aspen Colorado,
called biofeedback
 “Alpha training” adopted by flower 1978 Science paper
culture of late 1960s, and practitioners
oversold its claims

23. History of SMR biofeedback
 In 1960s Mercury astronauts
claimed they saw natives
waving at them when the flew
over the Pacific.(i.e., they
hallucinated)
 In 1967, Gordon Allies,
inventor of amphetamine, was
contracted to test toxicity of
the Mercury capsule rocket
fuel with David Fairchild
 However Allies tested another MB Sterman
chemical compound on
himself and shortly died,
before contract over. Fairchild
asked Sterman to help finish
work.

24. Sterman was studying EEG-
behavioral correlates in cats

25. If EEG behavior is like any other behavior, it
could be shaped with operant conditioning
 Two prominent rhythms in cat EEG – SMR and PRS
• Couldn’t train PRS, but could train SMR
• More on the PRS later

26. Cat Wireheads: cortical electrodes, not brain
stem or hypothalamic
 Cats often used in
electrophysiology
because head size
the same
regardless of
breed, unlike
dogs

27. 10 cats trained to produce SMR (sensorimotor
activity over motor strip) for chicken broth & milk

28. Acquisition resembles normal
behavior under O.C. training

29. Classic abundance response at
extinction

30. History of SMR biofeedback
 Then Sterman and Fairchild went on to another study,
testing rocket fuel on 50 cats, 10 from Sterman’s previous
SMR training study.
 Inject 100 mg/kg or so of fuel into each cat
• After one hour, all usually go into grand mal
 but not all - 7 delayed, 3 not at all.
• seizure thresholds changed in these 10
• Not explainable by placebo (“i shall please” in Latin) as
cats didn’t know what to expect, and experimenter blind
because effect was entirely unexpected

31. Sterman et al (1967) showing usual toxic
prodrome and resistance to MMH-
induced seizures in a subgroup
Time Avg 2 hours+ for seizures
with EEG trained cats
vs. 1 hour for normal
cats
NASA Rocket fuel

32. History of SMR biofeedback
 Replicated findings in monkeys, then moved to humans at
colleagues urging.
 Human epileptics
• First case study published in EEG & Clin Neurophysiology
• N=4 study, 65% seizure reduction, in Epilepsia 1976
• Then n=8, ABA three-year study, Epilepsia 1978
• Finally, full blown study funded by NIH
 Sham control, n=24, three years
 Double yoked n=8, n=8 NF, n=8 log books
 many went seizure free
 controls after study received NF
 Reliable increase in sleep spindle density and
decreased awakenings

33. A major study showed 60% reduction
in seizures 12 months after training

34. Turf war with medicine
 In 1982 Sterman’s NIH grant for 3 y was
funded, but then they demanded double
blind after approving the initial design,
then they pulled funding saying goals
already reached
 Cost of temporal lobe resection for
epilepsy = $200,000
• Money lost if patient undergoes neurotherapy
successfully

35. Review of 19 studies with EEG
Biofeedback for Epilepsy*
Medical Journal, Jan 2000
 82% of studies demonstrated
significant seizure reduction
 Average reduction exceeded 50%.
 Studies reported reduction in
seizure severity.
 About 5% had complete control for
up to one year
* Sterman, MB (2000). Basic Concepts and Clinical Findings in the
Treatment of Seizure Disorders with EEG Operant Conditioning.
Clinical EEG, 31(1), 45-55.

37. SMR attenuated (compared to cat subdural recordings) but
also present at the scalp in humans

38. Mechanisms of SMR training
 Enhancing
GABA
circuitry
involved in
motor
regulation,
dampening
excitability to
sensorimotor
excitation

39. 10-20 International System of Electrode Placement

40. History of Motoric Hyperexcitability
 1905: Hyperkinetic syndrome
(George Frederic Still, Lancet)
• “wanton destructiveness and a deficit in
moral behavior”
 Now known to be due to slowed maturation
• only partly related to will power, if at all
 Lubar (1975) ABA study, n=4
• Cz theta/beta ratio

41. Patterns of behavior indicative of ADHD
 Inattentive
• Easily distracted
• Fails to pay attention to details
 makes careless mistakes
 rarely follows directions completely or properly
• Forgets things needed to complete tasks (e.g., pencils)
 Hyperactive
• Unable to sit still
 Leaves seat when sitting expected or instructed
• Talks non-stop
 Impulsive
• Unable to suppress impulses
 inappropriate comments or shouts out answers early
• Hits
• Often puts oneself in danger, such as dashes into street

42. Attention Deficit Hyperactivity Disorder
 ADHD affects 2 million children in USA
• 5% of all boys
• 2% of all girls
 ~ 60% will remain symptomatic as adults
 1 M children take Rx to control hyperactivity.
 Genetic component: MZ concordance is 75-91%
 EEG frontal slowing due to immature frontal lobe
in impulsive subtype

43. Ritalin
 Controversy
 Commonly prescribed drug for children
• Worries about long-term effects.
• No studies on children who have taken
Ritalin > 14 months.
• Very similar to cocaine in composition
and effect

44. Monastra study – ADHD and biofeedback
vs. stimulant therapy
 100 ADHD children, ages 6-19, inattentive or combined types
 1-year multimodal outpatient program
• included Ritalin, parent counseling, academic support
 51 with EEG biofeedback
 RESULTS
• Post Tx assessments with and without stimulant therapy.
 Ritalin produced significant improvement on TOVA and ADDES
• Did not sustain when Ritalin removed
 EEG biofeedback group sustained gains when Ritalin removed.

46. First Year of specific
Neurofeedback Application
 1967 SMR conditioning in general
 1973 Epilepsy
 1975 Peak Performance
 1976 ADHD
 1977 Addiction
 1978 Anxiety disorders
 1978 Learning disabilities
 1980 Sleep Disorders
 1995 Brain Injury
 1995 Lyme's Disease
 1996 CFS
 1997 Mood disorders

47. Neurotherapy -start
 Revives Hess’ CNS
model of 1950s
• overaroused
• underaroused
 Added by Othmers
• instability
 Related issue of
plasticity
• Cajal thought
adult brain fixed
• finally countered
by Peter Eriksson
1998

48. Most important figure in behavioral
neuroscience (i.e., psychology)

49. Elegant design to counter any
intrinsic (non-contextual) reward

50. Earned PRS

51. PRS and learning

52. PRS characteristics
 Reward-based inhibition of MRF
• Mesencephalic Reticular Formation (originally called ARF) –
turns off the DC, i.e., volitional aspect of mind
 PRS does not occur initially
• animal must be fully habituated to environment
• any novelty or change will disrupt it.
• Light must also be on for PRS to emerge, even
when “light off” is a signal of food delivery trials.
 3-5 s burst indistinguishable from sleep onset or SWS
 Signal transmission in thalamus (LGN) and cortex is
suppressed by PRS (similar to SWS)

54. Unresponsive during PRS, like sleep

55. PRS (6-9 Hz in cats, 8-13 Hz in humans)

56. Alpha burst reflect preparation

57. Impact human learning

58. Field of Neuroregulation
 Clinical aspects
• Thalamocortical dysrhythmias
 Cognition
• Time binding
• Information processing, recruitment
 ERD and ERS

60. NF Practice
Therapist and client/game screen
Therapist Monitor
EEG
Sensors
Feedback Screen

61. Game provides client feedback
Mazes

62. Space Race

63. The Therapist Screen
Raw
Inhibit
Reward
Inhibit

64. Scoring Charts Provide
Periodic Feedback

65. A normal looking EEG is small in height
Small EEG

66. Reducing excessive (tall) slow brain
waves helps the brain function better
Examples of
excessive slow
brainwaves

67. Courtesy of
Example of EEG Brain Map Q-Metrx

68. This man has way too much alpha with
his eyes open. He’s got problems with
obsessive thinking – getting “stuck”
Slow alpha increased with eyes open. That’s not normal.

69. PRE/POST ASSESSMENTS
Male, age 9. Drawing before
Neurofeedback training

70. Male, age 9.
Drawing after 4
months of
Neurofeedback
training, 5/2/95

71. Child’s Family Drawing at
Beginning of NF - 8/3/94

72. Drawing after Twenty Sessions -
9/8/94

73. Drawing after forty sessions
-11/25/94

74. Neurofeedback Outcome 2003
Courtesy of Moshe Perl, Ph.D.
TOVA Summary - 53 Subjects
Pretreatment 20 sessions 20 or more sessions
neurofeedback
120
Standard Score
110
102
100
100
90 89 89
86 86 86 85
82
80
80
70
70 68
60
50
40
Inattention Impulsivity Response Time Variability

75. One year follow-up
TOVA Follow-up Summary - (n=16)
Courtesy of Moshe Perl,
Ph.D.
Pretreatment 14 Months
Post Treatment Followup
120
110
103 105106
100 99 97
92 94
Standard Score
92
90 88
84
80 80
74
70
60
50
40
Inattention Response Time
Impulsivity Variability

76. Brain-Computer Interface (BCI)
Muscle-independent communication
channel
 Two general approaches:
• rhythm generation (neurofeedback approach)
• natural correlates (QEEG assessment approach)
 Greatest obstacles
• Humans habituate
• Speed is slow, thus motivation must be high
 Training also slower for patients, generally, than normals
• Interference and distraction (a divided attention task)
 Current formulations requires a patient to pay attention to
contents of communication while simultaneously following
generative rules of the communication device.
• Impaired visual systems
• Instability, noise and/or lack of our understanding of human
EEG

77. Approaches
 QEEG approach
• P300
• VEP
 Neurofeedback
• Motor imagery
• SMR incidence
• Slow potentials

79. Speeds are generally characters
per minute
Imagery
 1. think about nothing
 2. solve multiplication
 3. mentally rotate
 4. mentally write a letter to friend
 5. visualize numbers being written on board sequentially

80. BCI Applications
 Workload shunting
 Augmented reality (instead of VR)
 Locked-in syndrome
• ALS, encephalitis, brainstem stroke
 Quality of life, extreme social restriction
• Other applications not yet
imagined or designed

81. BCI (for kaiser’s notes only)

82. Team Projects
 EC1 baseline  Search literature to
 EO1 baseline identify two tasks studied
 Task 1 by EEG or fMRI, and the
complementary sites
• Site 1 activates, Site 2 no
change
 Task 2
• Site 1 no change, Site 2
activates
 EC2 baseline
 EO2 baseline
 Limitations: Macrostate,
Alpha activity only, post-
hoc artifact control

84. Dedicated to my family for
making everything worthwhile

85. READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER
THANK YOU
My sincere thanks to MEDHA SRINVASAN
SECRETARY- SOCIETY FOR ADVANCEMENT
OF BRAIN ANALYSIS- INDIAN CHAPTER