Is brain-behavior behavior? If so, it can be conditioned just like other behaviors If so, it can be conditioned just like other behaviors In 1960s, certain.

Is brain-behavior behavior?Is brain-behavior behavior?

If so, it can be If so, it can be conditioned just conditioned just like other like other behaviorsbehaviors

In 1960s, certain In 1960s, certain rhythms could be rhythms could be “trained”“trained”

Led to Led to Neurotherapy and Neurotherapy and Brain-Computer Brain-Computer interfaces (BCI)interfaces (BCI)

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

Electrical stimulation of brains (ESB)Electrical stimulation of brains (ESB)

Electrical stimulation of brains of rats - Electrical stimulation of brains of rats - James Olds in 1950s; James Olds in 1950s; • Jacobsen and Torkildsen replicated Jacobsen and Torkildsen replicated

work in humans;work in humans;• some epileptics stimulated some epileptics stimulated

themselves into convulsionsthemselves into convulsions

INTRA-CRANIAL SELF-INTRA-CRANIAL SELF-STIMULATIONSTIMULATION

Rodent wireheadsRodent wireheads• 0.0005 amps whenever rat pushed lever0.0005 amps whenever rat pushed lever• Up to 10,000 bar-presses an hour recorded Up to 10,000 bar-presses an hour recorded • Animals self-stimulate > 24 hrs continuously without Animals self-stimulate > 24 hrs continuously without

rest, and cross electrified grid to gain access to lever rest, and cross electrified grid to gain access to lever • Reward center: Medial forebrain bundle passing through Reward center: Medial forebrain bundle passing through

lateral hypothalamus and ventral tegmentumlateral hypothalamus and ventral tegmentum• Other brain centers are aversive, such as Other brain centers are aversive, such as periaqueductalperiaqueductal

grey matter (PAG)grey matter (PAG)

• Ventral tegmental area (Ventral tegmental area (VTAVTA) neurons manufacture ) neurons manufacture dopaminedopamine and they are under continuous inhibition by and they are under continuous inhibition by gamma-aminobutyric acid (gamma-aminobutyric acid (GABAGABA) system, an important ) system, an important component of the ”final common pathway" of reward, component of the ”final common pathway" of reward, implicated in addiction, mood, and learning.implicated in addiction, mood, and learning.

Delgado, Primate wireheads, and Delgado, Primate wireheads, and Circuitry manCircuitry man

Electrical stimulation of brains Electrical stimulation of brains (intracranial stimulation)(intracranial stimulation)

Pavlov conditioning experimentsPavlov conditioning experiments• Tone for food, buzzer for shock –Tone for food, buzzer for shock –• Moved them closer together in timeMoved them closer together in time• confounded dog fell asleep confounded dog fell asleep

Termed “internal inhibition”Termed “internal inhibition” Animal can close down own Animal can close down own

systems to avoid stresssystems to avoid stress

Neal E Miller trained autonomic functionsNeal E Miller trained autonomic functions• Dogs salivate to get foodDogs salivate to get food• Rats control heartrate to get waterRats control heartrate to get water

History of BiofeedbackHistory of Biofeedback JH Bair, 1901, instrument used to teach ear wigglingJH Bair, 1901, instrument used to teach ear wiggling

In early 20th century, J.H. Schultz in Germany developed a In early 20th century, J.H. Schultz in Germany developed a technique called technique called Autogenic TrainingAutogenic Training. Verbal instructions are . Verbal instructions are used to guide a person to a more relaxed and controlled used to guide a person to a more relaxed and controlled physiological state. physiological state. • The method flourished, and the results were reported upon by The method flourished, and the results were reported upon by

Wolfgang Luthe in 1969 in the United States.Wolfgang Luthe in 1969 in the United States. Increased awareness in Western world of yogic ability to Increased awareness in Western world of yogic ability to

alter physiology volitionally. E.g., a yogi could survive in a alter physiology volitionally. E.g., a yogi could survive in a sealed box by voluntarily reducing his metabolic rate sealed box by voluntarily reducing his metabolic rate significantly, surviving hours with a limited supply of significantly, surviving hours with a limited supply of oxygen. oxygen.

Peripheral biofeedback techniques include Peripheral biofeedback techniques include • GSR, thermal, breathing, cardiac GSR, thermal, breathing, cardiac

History of EEG biofeedbackHistory of EEG biofeedback 1934, Adrian watched his EEG in front of 1934, Adrian watched his EEG in front of

oscillograph and created alpha at willoscillograph and created alpha at will

Alpha biofeedback or deep statesAlpha biofeedback or deep states• Joe Kamiya at Univ of Chicago, 1958+Joe Kamiya at Univ of Chicago, 1958+

Kamiya 1958Kamiya 1958• 1st subject - 60 tones and 60 1st subject - 60 tones and 60

guesses, half rightguesses, half right• 2nd trial, 65 % correct2nd trial, 65 % correct• 3rd 85% correct3rd 85% correct• 4th, after a few mistakes, 400 correct 4th, after a few mistakes, 400 correct

in a rowin a row 1968 first congress in Aspen Colorado, 1968 first congress in Aspen Colorado,

called biofeedbackcalled biofeedback

““Alpha training” adopted by flower Alpha training” adopted by flower culture of late 1960s, and practitioners culture of late 1960s, and practitioners oversold its claimsoversold its claims

1978 Science paper1978 Science paper

History of SMR biofeedbackHistory of SMR biofeedback In 1960s Mercury astronauts In 1960s Mercury astronauts

claimed they saw natives claimed they saw natives waving at them when the flew waving at them when the flew over the Pacific.(i.e., they over the Pacific.(i.e., they hallucinated)hallucinated)

In 1967, Gordon Allies, In 1967, Gordon Allies, inventor of amphetamine, was inventor of amphetamine, was contracted to test toxicity of contracted to test toxicity of the Mercury capsule rocket the Mercury capsule rocket fuel with David Fairchildfuel with David Fairchild

However Allies tested another However Allies tested another chemical compound on chemical compound on himself and shortly died, himself and shortly died, before contract over. Fairchild before contract over. Fairchild asked Sterman to help finish asked Sterman to help finish work.work.

MB StermanMB Sterman

Sterman was studying EEG-Sterman was studying EEG-behavioral correlates in catsbehavioral correlates in cats

If EEG behavior is like any other behavior, it If EEG behavior is like any other behavior, it could be shaped with operant conditioningcould be shaped with operant conditioning

Two prominent rhythms in cat EEG – SMR and PRSTwo prominent rhythms in cat EEG – SMR and PRS• Couldn’t train PRS, but could train SMR Couldn’t train PRS, but could train SMR • More on the PRS laterMore on the PRS later

Cat Wireheads: cortical electrodes, not brain Cat Wireheads: cortical electrodes, not brain stem or hypothalamicstem or hypothalamic

Cats often used in Cats often used in electrophysiology electrophysiology because head size because head size the same the same regardless of regardless of breed, unlike breed, unlike dogsdogs

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

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

Classic abundance response at Classic abundance response at extinctionextinction

History of SMR biofeedbackHistory of SMR biofeedback Then Sterman and Fairchild went on to another study, Then Sterman and Fairchild went on to another study,

testing rocket fuel on 50 cats, 10 from Sterman’s previous testing rocket fuel on 50 cats, 10 from Sterman’s previous SMR training study.SMR training study.

Inject 100 mg/kg or so of fuel into each catInject 100 mg/kg or so of fuel into each cat• After one hour, all usually go into grand malAfter one hour, all usually go into grand mal

but not all - 7 delayed, 3 not at all.but not all - 7 delayed, 3 not at all.

• seizure thresholds changed in these 10seizure thresholds changed in these 10

• Not explainable by placebo (“i shall please” in Latin) as Not explainable by placebo (“i shall please” in Latin) as cats didn’t know what to expect, and experimenter blind cats didn’t know what to expect, and experimenter blind because effect was entirely unexpectedbecause effect was entirely unexpected

Sterman et al (1967) showing usual toxic Sterman et al (1967) showing usual toxic prodrome and resistance to MMH-prodrome and resistance to MMH-induced seizures in a subgroupinduced seizures in a subgroup

NASA Rocket fuel

Avg 2 hours+ for seizures with EEG trained cats vs. 1 hour for normal cats

Time

History of SMR biofeedbackHistory of SMR biofeedback Replicated findings in monkeys, then moved to humans at Replicated findings in monkeys, then moved to humans at

colleagues urging.colleagues urging.

Human epilepticsHuman epileptics• First case study published in EEG & Clin NeurophysiologyFirst case study published in EEG & Clin Neurophysiology• N=4 study, 65% seizure reduction, in Epilepsia 1976 N=4 study, 65% seizure reduction, in Epilepsia 1976 • Then n=8, ABA three-year study, Epilepsia 1978Then n=8, ABA three-year study, Epilepsia 1978• Finally, full blown study funded by NIHFinally, full blown study funded by NIH

Sham control, n=24, three yearsSham control, n=24, three years Double yoked n=8, n=8 NF, n=8 log booksDouble yoked n=8, n=8 NF, n=8 log books many went seizure freemany went seizure free controls after study received NFcontrols after study received NF Reliable increase in sleep spindle density and Reliable increase in sleep spindle density and

decreased awakeningsdecreased awakenings

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

Turf war with medicineTurf war with medicine

In 1982 Sterman’s NIH grant for 3 y was In 1982 Sterman’s NIH grant for 3 y was funded, but then they demanded double funded, but then they demanded double blind after approving the initial design, blind after approving the initial design, then they pulled funding saying goals then they pulled funding saying goals already reachedalready reached

Cost of temporal lobe resection for Cost of temporal lobe resection for epilepsy = $200,000epilepsy = $200,000• Money lost if patient undergoes neurotherapy Money lost if patient undergoes neurotherapy

successfullysuccessfully

Review of 19 studies with EEG Review of 19 studies with EEG Biofeedback for Epilepsy*Biofeedback for Epilepsy*Medical Journal, Jan 2000Medical Journal, Jan 2000

82% of studies demonstrated 82% of studies demonstrated significant seizure reduction significant seizure reduction

Average reduction exceeded 50%.Average reduction exceeded 50%. Studies reported Studies reported reduction in reduction in

seizure severityseizure severity.. About 5% had complete control for About 5% had complete control for

up to one year up to one year

* Sterman, MB (2000). Basic Concepts and Clinical Findings in the * Sterman, MB (2000). Basic Concepts and Clinical Findings in the Treatment of Seizure Disorders with EEG Operant Conditioning. Treatment of Seizure Disorders with EEG Operant Conditioning. Clinical Clinical EEG, 31(1EEG, 31(1), 45-55.), 45-55.

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

Mechanisms of SMR trainingMechanisms of SMR training Enhancing Enhancing

GABA GABA circuitry circuitry involved in involved in motor motor regulation, regulation, dampening dampening excitability to excitability to sensorimotor sensorimotor excitationexcitation

10-20 International System of Electrode Placement10-20 International System of Electrode Placement

History of Motoric HyperexcitabilityHistory of Motoric Hyperexcitability

1905: Hyperkinetic syndrome1905: Hyperkinetic syndrome(George Frederic Still, Lancet)(George Frederic Still, Lancet)

• ““wanton destructiveness and a deficit in wanton destructiveness and a deficit in moral behavior”moral behavior”

Now known to be due to slowed maturationNow known to be due to slowed maturation• only partly related to will power, if at allonly partly related to will power, if at all

Lubar (1975) ABA study, n=4Lubar (1975) ABA study, n=4• Cz theta/beta ratioCz theta/beta ratio

Patterns of behavior indicative of ADHDPatterns of behavior indicative of ADHD Inattentive Inattentive

• Easily distracted Easily distracted • Fails to pay attention to detailsFails to pay attention to details

makes careless mistakes makes careless mistakes rarely follows directions completely or properlyrarely follows directions completely or properly

• Forgets things needed to complete tasks (e.g., pencils)Forgets things needed to complete tasks (e.g., pencils)

Hyperactive Hyperactive • Unable to sit still Unable to sit still

Leaves seat when sitting expected or instructed Leaves seat when sitting expected or instructed • Talks non-stop Talks non-stop

Impulsive Impulsive • Unable to suppress impulses Unable to suppress impulses

inappropriate comments or shouts out answers earlyinappropriate comments or shouts out answers early• Hits Hits • Often puts oneself in danger, such as dashes into streetOften puts oneself in danger, such as dashes into street

Attention Deficit Hyperactivity DisorderAttention Deficit Hyperactivity Disorder

ADHD affects 2 million children in USA ADHD affects 2 million children in USA • 5% of all boys5% of all boys• 2% of all girls2% of all girls

~ 60% will remain symptomatic as adults~ 60% will remain symptomatic as adults

1 M children take Rx to control hyperactivity.1 M children take Rx to control hyperactivity.

Genetic component: MZ concordance is 75-91% Genetic component: MZ concordance is 75-91%

EEG frontal slowing due to immature frontal lobe EEG frontal slowing due to immature frontal lobe in impulsive subtypein impulsive subtype

RitalinRitalin

ControversyControversy CCommonly prescribed drug for childrenommonly prescribed drug for children

• Worries about long-term effects. Worries about long-term effects. • No studies on children who have taken No studies on children who have taken

Ritalin > 14 months. Ritalin > 14 months. • Very similar to cocaine in composition Very similar to cocaine in composition

and effectand effect

Monastra study – ADHD and biofeedback Monastra study – ADHD and biofeedback vs. stimulant therapyvs. stimulant therapy

100 ADHD children, ages 6-19, inattentive or combined types 100 ADHD children, ages 6-19, inattentive or combined types 1-year multimodal outpatient program 1-year multimodal outpatient program

• included Ritalin, parent counseling, academic supportincluded Ritalin, parent counseling, academic support 51 with EEG biofeedback 51 with EEG biofeedback

RESULTSRESULTS• Post Tx assessments with and without stimulant therapy. Post Tx assessments with and without stimulant therapy.

Ritalin produced significant improvement on TOVA and ADDESRitalin produced significant improvement on TOVA and ADDES• Did not sustain when Ritalin removedDid not sustain when Ritalin removed

EEG biofeedback group sustained gains when Ritalin removed. EEG biofeedback group sustained gains when Ritalin removed.

First Year of specific First Year of specific Neurofeedback ApplicationNeurofeedback Application

1967 SMR conditioning in general 1967 SMR conditioning in general 1973 Epilepsy 1973 Epilepsy 1975 Peak Performance 1975 Peak Performance 1976 ADHD 1976 ADHD 1977 Addiction 1977 Addiction 1978 Anxiety disorders 1978 Anxiety disorders 1978 Learning disabilities 1978 Learning disabilities 1980 Sleep Disorders 1980 Sleep Disorders 1995 Brain Injury 1995 Brain Injury 1995 Lyme's Disease 1995 Lyme's Disease 1996 CFS 1996 CFS 1997 Mood disorders 1997 Mood disorders

Neurotherapy -startNeurotherapy -start Revives Hess’ CNS Revives Hess’ CNS

model of 1950s model of 1950s • overaroused overaroused • underaroused underaroused

Added by OthmersAdded by Othmers• instabilityinstability

Related issue of Related issue of plasticityplasticity• Cajal thought Cajal thought

adult brain fixedadult brain fixed• finally countered finally countered

by Peter Eriksson by Peter Eriksson 19981998

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

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

Earned PRSEarned PRS

PRS and learningPRS and learning

PRS characteristicsPRS characteristics Reward-based inhibition of MRFReward-based inhibition of MRF

• Mesencephalic Reticular Formation (originally called ARF) – Mesencephalic Reticular Formation (originally called ARF) – turns off the DC, i.e., volitional aspect of mindturns off the DC, i.e., volitional aspect of mind

PRS does not occur initially PRS does not occur initially • animal must be fully habituated to environmentanimal must be fully habituated to environment• any novelty or change will disrupt it. any novelty or change will disrupt it. • Light must also be on for PRS to emerge, even when Light must also be on for PRS to emerge, even when

“light off” is a signal of food delivery trials.“light off” is a signal of food delivery trials.

3-5 s burst indistinguishable from sleep onset or SWS3-5 s burst indistinguishable from sleep onset or SWS

Signal transmission in thalamus (LGN) and cortex is Signal transmission in thalamus (LGN) and cortex is suppressed by PRS (similar to SWS)suppressed by PRS (similar to SWS)

Unresponsive during PRS, like sleepUnresponsive during PRS, like sleep

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

Alpha burst reflect preparationAlpha burst reflect preparation

Impact human learningImpact human learning

Field of NeuroregulationField of Neuroregulation

Clinical aspectsClinical aspects• Thalamocortical dysrhythmias Thalamocortical dysrhythmias

CognitionCognition• Time bindingTime binding• Information processing, recruitmentInformation processing, recruitment

ERD and ERSERD and ERS

Feedback Screen

Therapist Monitor

EEG Sensors

NF PracticeNF PracticeTherapist and client/game screenTherapist and client/game screen

Game provides client feedbackGame provides client feedback

Mazes

Space RaceSpace Race

Reward

The Therapist Screen

Raw

Inhibit

Inhibit

Scoring Charts Provide Periodic Feedback

Operant Conditioning

A normal looking EEG is small in heightA normal looking EEG is small in height

Small EEG

Reducing Reducing excessive (tall) slow brain excessive (tall) slow brain waves waves helps the brain function betterhelps the brain function better

Examples of excessive slow brainwaves

Example of EEG Brain MapExample of EEG Brain MapCourtesy of Q-Metrx

This man has way too much alpha with This man has way too much alpha with his eyes open. He’s got problems with his eyes open. He’s got problems with obsessive thinking – getting “stuck”obsessive thinking – getting “stuck”

Slow alpha increased with eyes open. That’s not normal.

PRE/POST ASSESSMENTSPRE/POST ASSESSMENTSMale, age 9. Drawing before Male, age 9. Drawing before

Neurofeedback trainingNeurofeedback training

Male, age 9. Male, age 9. Drawing after 4 Drawing after 4

months of months of Neurofeedback Neurofeedback training, 5/2/95training, 5/2/95

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

Drawing after Twenty Sessions - Drawing after Twenty Sessions - 9/8/949/8/94

Drawing after forty sessions -Drawing after forty sessions -11/25/9411/25/94

Neurofeedback Outcome 2003Courtesy of Moshe Perl, Ph.D.

89

102

898586

100

86

80

70

8682

68

Inattention Impulsivity Response Time Variability

40

50

60

70

80

90

100

110

120

Sta

nd

ard

Sco

re

Pretreatment 20 sessions 20 or more sessionsneurofeedback

TOVA Summary - 53 Subjects

One year follow-upOne year follow-upCourtesy of Moshe Perl, Ph.D.

103106

949799

105

92 92

80

8884

74

InattentionImpulsivity

Response TimeVariability

40

50

60

70

80

90

100

110

120

Sta

nd

ard

Sco

re

Pretreatment

Post Treatment

14 MonthsFollowup

TOVA Follow-up Summary - (n=16)