1 2

EVIDENCE FOR ABERRANT SENSORY AND MOTOR LEARNING IN FOCAL DYSTONIA:

IMPLICATIONS FOR LEARNING BASED

3

SENSORIMOTOR TRAINING TO IMPROVE

4

MOTOR CONTROL AND COGNITION

5

BY NANCY BYL

6 7

THE MODERATOR:

I WANT TO THANK YOU VERY MUCH

8

FOR BEARING THE TIME FOR THE FIRST LECTURE.

IT'S MY

9

GREAT PLEASURE TO INTRODUCE THE SECOND SPEAKER TODAY.

10

THIS IS DR. NANCY BYL.

11

THERAPY, UNIVERSITY OF CALIFORNIA SAN FRANCISCO, AND

12

SHE WILL TALK TO US TODAY ABOUT EVIDENCE FOR ABERRANT

13

SENSORY AND MOTOR LEARNING IN FOCAL DYSTONIA:

14

IMPLICATIONS FOR LEARNING BASED SENSORIMOTOR TRAINING

15

TO IMPROVE MOTOR CONTROL AND COGNITION. DR. BYL:

16

SHE'S A PROFESSOR OF PHYSICAL

DR. BYL.

I WILL DESCRIBE THE APPLICATIONS OF

17

BASIC SCIENCE TO LEARNING BASED TRAINING AND HIGHLIGHT

18

MORE SPECIFICALLY SENSORIMOTOR TRAINING AS IT RELATES

19

TO PATIENTS WHO I BELIEVE EXPRESS WHAT IS CALLED AN

20

ABERRANT LEARNING PHENOMENA LEADING TO ABNORMAL MOTOR

21

CONTROL.

22

I WILL DISCUSS WHAT TREATMENT POTENTIAL EXISTS WHEN

23

APPLYING THIS THEORY TO PATIENTS, AND I ALSO WILL GIVE

24

EXAMPLES OF TRAINING, AND SUMMARIZE THE APPLICATIONS

25

AND THE EFFECTIVENESS OF THIS PARADIGM TO OTHER

I WILL SHARE THE EVIDENCE BEHIND THIS THEORY.

1

1

PATIENTS.

2

IT HAS BEEN WELL ACCEPTED THAT THE CENTRAL

3

NERVOUS SYSTEM MAKES ITS GREATEST CHANGES DURING THE

4

GROWING YEARS AS A PART OF NORMAL DEVELOPMENT AND

5

MATURATION.

6

SYSTEM CHANGES THROUGHOUT OUR LIFETIME IN RESPONSE TO

7

AGING, INJURY, AND DISEASE.

8

THAT WE CAN DRIVE CHANGES IN THE CENTRAL NERVOUS SYSTEM

9

WITH LEARNING-BASED TRAINING.

10

BUT TODAY WE ALSO KNOW THAT THE NERVOUS

WHAT IS MOST IMPORTANT IS

OUR POTENTIAL FOR NEURAL ADAPTATION, HOWEVER,

11

VARIES, AND IT VARIES BY OUR GENETICS, OUR BASIC

12

ANATOMY, OUR PHYSIOLOGY, OUR NEURAL TRANSMITTERS AND

13

HORMONES, AS WELL AS OUR PERSONALITY, OUR COMMITMENT,

14

AND OUR MOTIVATION FOR CHANGE.

15

OUR ABILITY TO CHANGE IS ALSO DEPENDENT ON

16

OUR ABILITY TO FACILITATE BETTER SIGNALS, TO BALANCE

17

EXCITATION AND INHIBITION OF OUR NEURAL NETWORKS, AS

18

WELL AS OUR OPPORTUNITY TO TAKE ADVANTAGE OF AND

19

PARTICIPATE IN LEARNING-BASED ACTIVITIES WITHIN OUR

20

ENVIRONMENT.

21

IN THIS CLASSIC DIAGRAM OF PLASTICITY BY

22

MERZENICH AND JENKINS, YOU CAN SEE THAT WE CAN CHANGE

23

NEURAL STRUCTURE BY ATTENDED REPETITIVE PRACTICE.

24

THIS CASE IN A1 AND 2, YOU CAN SEE THE EXPANSION OF THE

25

CORTICAL REPRESENTATION OF THE DIGITS AFTER FOLLOWING A

2

IN

1

SENSORY ATTENDED RETRAINING PROGRAM.

2

CAN SEE THAT THE NORMAL RECEPTIVE FIELDS ON THE HAND

3

BECOME SMALLER WITH TRAINING, THEY BECOME MORE DENSE

4

AND MORE NUMEROUS, MAKING THE REPRESENTATION MORE

5

SPECIFIC.

6

ON THE RIGHT YOU

LEARNING BEGINS WHEN INFORMATION IS

7

TRANSMITTED FROM THE PERIPHERAL NERVOUS SYSTEM THROUGH

8

THE RECEPTORS AND THE PERIPHERAL NERVES TO THE SPINAL

9

CORD.

ADAPTIVE CHANGES ARE SEEN THROUGHOUT THE NERVOUS

10

SYSTEM, EVEN THOUGH MOST OF OUR BASIC SCIENCE STUDIES

11

ON PLASTICITY HAVE FOCUSED ON THE CORTEX.

12

UNFORTUNATELY EVEN THE HEALTHIEST NERVOUS SYSTEM HAS A

13

FINITE LIMIT FOR CHANGE BASED ON ANATOMICAL AND

14

PHYSIOLOGICAL CONSTRAINTS, INCLUDING TIME CONSTANTS,

15

COMPETITION FOR MYELIN, KEEPING TRACK OF FEEDBACK, AND

16

TEMPORAL INTEGRATION.

17

LEARNING MAY GO ASKEW, WHICH WE REFER TO AS NEGATIVE OR

18

ABERRANT LEARNING.

WHEN THESE LIMITS ARE REACHED,

19

LEARNING CAN BE ABERRANT WHEN AN INDIVIDUAL

20

HAS LOW SELF-ESTEEM, FEELS NEGATIVE, IS UNDER STRESS,

21

RESORTS TO NONLEARN OR HABITUAL BEHAVIORS, HAS AN

22

INJURY OR A DISEASE, OR EXCEEDS THE LIMITS OF THESE

23

NEURAL CONSTRAINTS.

24 25

SOME OF THE ABERRANT LEARNING CONDITIONS INCLUDE BAD HABITS LIKE SMOKING, DISEASE, LIMITATIONS

3

1

IN STRUCTURE, A COMPENSATORY LIMP, FOR EXAMPLE, FROM

2

PAIN OR EXCESSIVE ADAPTATION OF THE NERVOUS SYSTEM

3

FOLLOWING NEAR SIMULTANEOUS, NEAR STEREOTYPICAL

4

REPETITIONS. IN THIS PARTICULAR DIAGRAM YOU CAN SEE THIS

5 6

IS AN EXAMPLE OF ABERRANT LEARNING, THE CORTICAL

7

SENSORY CHANGES THAT HAVE OCCURRED IN THE DIGITS

8

FOLLOWING EXCESSIVE REPETITIVE STEREOTYPICAL MOVEMENT.

9

THE CORTICAL REPRESENTATION IN THIS PARTICULAR CASE IS

10

REDUCED, BUT IN THIS PICTURE YOU SEE THAT THE RECEPTIVE

11

FIELDS BECOME VERY LARGE AND NOT ONLY OVERLAP ADJACENT

12

DIGITS, BUT ALSO OVERLAP THE DORSAL AND GLABROUS

13

SURFACE OF THE HAND.

14

DIFFERENTIATE INDIVIDUAL DIGITS AND CONTROL THEIR

15

MOVEMENT.

THE BRAIN CAN NO LONGER

FOCAL HAND DYSTONIA MAY BE AN EXAMPLE OF

16 17

EXCESSIVE STEREOTYPICAL NEAR SIMULTANEOUS REPETITIVE

18

MOVEMENTS OF THE HAND PRACTICED OVER LONG PERIODS OF

19

TIME.

20

OF INVOLUNTARY IN RANGE CO-CONTRACTIONS OF THE FLEXORS

21

AND EXTENSORS WHEN PERFORMING A TARGET TASK.

22

EXCESSIVE EXCITATION AND AN ADEQUATE INHIBITION.

23

HAND DYSTONIA MAY ACTUALLY ALSO REPRESENT A LEARNED

24

CONDITION IN GIFTED PERFECTIONISTS WHO PERFORM HIGHLY

25

REPETITIVE WORK AND HAVE AN UNUSUALLY ADAPTIVE PLASTIC

IT IS DEFINED AS A DISABLING MOVEMENT DISORDER

4

THERE IS FOCAL

1

NERVOUS SYSTEM THAT ALLOWS THEM TO ACHIEVE SUPERIOR

2

RAPID SKILLED MOVEMENTS, AS YOU SEE IN THIS PIANIST AND

3

ALSO IN THIS CARTOONIST.

4

OCCUPATIONAL FOCAL DYSTONIA HAS BEEN CONSIDERED LOW, IN

5

RECENT YEARS INCREASED STRESS IN SOCIETY, INCREASED

6

DEMAND FOR COMPUTER USE, INCREASED COMPETITION FOR

7

MUSICAL PERFORMANCE, AND INCREASED AWARENESS, THERE ARE

8

MORE CASES OF FOCAL DYSTONIA BEING DIAGNOSED.

ALTHOUGH THE INCIDENCE OF

FOR EXAMPLE, 50 TO 60 PERCENT OF MUSICIANS

9 10

HAVE PROBLEMS WITH REPETITIVE STRAIN INJURY.

11

APPROXIMATELY 10 PERCENT OF THEM MAY DEVELOP FOCAL HAND

12

DYSTONIA.

13

SCIENTISTS HAVE IDENTIFIED MANY DIFFERENT

14

GENES TO EXPLAIN THE ORIGIN OF GENERALIZED DYSTONIA;

15

HOWEVER, THE CONTROVERSY ON THE ETIOLOGY OF FOCAL HAND

16

DYSTONIA CONTINUES TO THIS DAY.

17

IS A LACK OF INHIBITION, THERE IS SOMETHING UNIQUE

18

ABOUT THE FOCAL OCCUPATIONALLY RELATED DYSTONIAS.

19

IS JUST VERY DIFFICULT TO EXPLAIN THE DISORDER IN TERMS

20

OF NEURAL STRUCTURE WHEN THE ABNORMAL MOVEMENTS ONLY

21

OCCUR WHEN PERFORMING A TARGET TASK OR WHEN MOVING A

22

PARTICULAR BODY PART.

23

WHILE MOST AGREE THERE

WHAT IS INTERESTING IS THAT ALL THE

24

INDIVIDUALS WHO HAVE THE GENE FOR DYSTONIA DO NOT

25

NECESSARILY DEVELOP A CLINICAL DYSTONIA.

5

FOCAL

IT

1

DYSTONIA IS UNDOUBTEDLY MULTIFACTORIAL.

2

PROBABLY AN ACCUMULATION AND AN INTERACTION OF MANY

3

RISK FACTORS THAT LEAD TO THE CLINICAL PRESENTATION OF

4

THE PROBLEM, INCLUDING GENETICS, NEUROPHYSIOLOGY,

5

SENSATION POTENTIAL FOR PLASTICITY, ENVIRONMENT,

6

BEHAVIORAL CHARACTERISTICS AND PERSONALITY.

7

THERE IS

CLEARLY THOSE AT RISK ARE INDIVIDUALS WITH A

8

TYPE A PERSONALITY WHO ARE CLEARLY PERFECTIONISTS AND

9

ARE DRIVEN TO WORK LONG HOURS UNDER STRESS OFTEN USING

10

UNSAFE BIOMECHANICS.

11

INJURY, MAYBE SOME PHYSICAL RESTRICTIONS, AND MAYBE

12

HAVE EXCESSIVE NEUROPLASTICITY.

13

THEY MAY HAVE ALSO HAD A PREVIOUS

IN PATIENTS WITH FOCAL DYSTONIA, THERE ARE

14

SEVERAL SENSORY DIFFERENCES THAT CAN BE NOTED.

15

OF ALL, THEY ALL HAVE A SENSORY TRICK, A PLACE THAT

16

THEY CAN TOUCH OR PROVIDE A CUTANEOUS INPUT THAT

17

DECREASES THE SEVERITY OF THE DYSTONIC POSTURING.

18

WHEN BOTULINUM TOXIN IS INJECTED TO STOP THE MUSCLE

19

CONTRACTIONS, THE FIRING PATTERN CHANGES AS IF THE

20

PROPRIACEPTIVE FEEDBACK ALLOWS OTHER MUSCLES TO COME

21

INTO ACTION.

22

FIRST

ALSO

LIDOCAINE CAN DECREASE SENSATION OF

23

PROPRIOCEPTION AND TEMPORARILY REDUCE THE CRAMPING.

24

INTERESTINGLY, MICROCURRENTS, WHICH IS NOT EVEN FELT OR

25

PERCEIVED BY NORMAL HEALTHY INDIVIDUALS, WILL ACTUALLY

6

1

STIMULATE THE FIRING OF THE MUSCLE AFFERENTS IN

2

PATIENTS WITH DYSTONIA.

3

STIMULATION, WHICH IS ALSO INHIBITORY IN NORMAL HEALTHY

4

PATIENTS, WILL, IN FACT, BE EXCITORY IN PATIENTS WITH

5

DYSTONIA.

6

IN ADDITION, TRANSMAGNETIC

THERE CLEARLY SEEMS TO BE AN IMBALANCE OF

7

INHIBITION AND EXCITATION IN THE PRESYNAPTIC FIRING IN

8

THE SENSORY CORTEX BOTH IN 3 A AND 3 B, AND INCREASED

9

THICKNESS OF THE GRAY MATTER IN 3 B HAS BEEN REPORTED.

10

ALTHOUGH OUR ORIGINAL STUDIES FOCUSED ON SENSORY

11

DEGRADATION, IN ESTABLISHED DYSTONIA, ABNORMAL

12

TOPOGRAPHY OF THE MAPS OF OTHER AREAS OF THE CORTEX

13

HAVE ALSO BEEN REPORTED.

14

THE BASAL GANGLIA, AS WELL AS THE SENSORIMOTOR AND

15

MOTOR CORTICES.

16

SPECIFICALLY IN THE THALAMUS,

CLINICALLY PATIENTS WITH FOCAL HAND DYSTONIA

17

HAVE ABNORMAL RESPONSES TO SENSORY EVOKED STIMULI AND

18

DEMONSTRATE DECREASED ACCURACY IN CUTANEOUS SENSATIONS,

19

HAPTIC EXPLORATION, AND SPATIAL ORIENTATION.

20

SO IT IS OUR HYPOTHESIS THAT EXCESSIVE,

21

REPETITIVE, STEREOTYPICAL, NEAR SIMULTANEOUS

22

STIMULATION TO THE DIGITS CAN DEGRADE THE CORTICAL HAND

23

REPRESENTATION, AND THIS WILL INTERFERE WITH VOLUNTARY

24

MOTOR CONTROL.

25

IN TRYING TO PROVE THIS HYPOTHESIS, SEVERAL

7

1

ANIMAL MODELS HAVE BEEN DESIGNED.

2

DESIGNED BOTH WITH RATS AS WELL AS WITH PRIMATES.

3

THESE TWO MODELS HAVE BEEN USED TO STUDY THE ETIOLOGY

4

OF REPETITIVE STRAIN INJURY AND FOCAL HAND DYSTONIA.

5

I'VE BEEN INVOLVED IN THE PRIMATE MODEL, AND WE ALSO

6

HAVE SOME VERY GOOD MODELS FOR STUDYING NEUROPLASTICITY

7

IN HUMAN SUBJECTS. MARY BARBE AND ANN BARR DEVELOPED A RAT MODEL

8 9

THESE HAVE BEEN

OF REPETITIVE STRAIN INJURY, TRAINING THEIR RATS 30

10

MINUTES TWICE A DAY FOR OVER SIX WEEKS TO REALLY REPORT

11

THE CONSEQUENCES OF REPETITIVE OVERUSE.

12

RESEARCHERS REPORT AN INTERESTING SEQUENCE OF EVENTS

13

STARTING WITH LOCAL INFLAMMATION ON THE TRAINED SIDE,

14

WHICH THEN BEGINS TO SPREAD TO THE UNTRAINED SIDE, AND

15

THEN CHANGES ARE MEASURED IN THE SPINAL CORD.

16

ULTIMATELY SOME OF THE RATS LOSE MOTOR CONTROL AND CAN

17

NO LONGER PERFORM THE TASK, AND THEN THESE CHANGES ARE

18

ALSO NOTED IN THE SENSORY AND MOTOR CORTEX WITH

19

ABNORMAL TOPOGRAPHY.

THESE

WE DEVELOPED TWO PRIMATE MODELS TO STUDY HAND

20 21

DYSTONIA.

ONE INVOLVED RAPID OPENING AND CLOSING OF

22

THE HAND AND THE SECOND TOUCHING TWO SEPARATE POINTS

23

QUICKLY AND SIMULTANEOUSLY.

24

RIGHT AND THE LEFT OF THE SCREEN.

25

TRAINING AT LEAST TWO-THIRDS OF THESE PRIMATES WHO

AND YOU SEE THOSE ON THE

8

WE DOCUMENT AFTER

1

DEVELOPED PROBLEMS IN MOTOR CONTROL.

2

WHAT WE CALLED ABERRANT LEARNING.

3

THE PRECISE REPRESENTATIONAL SPECIFICITY OF THE TRAINED

4

SIDE.

5

CORTICAL REPRESENTATION, THERE WERE LARGE RECEPTIVE

6

FIELDS OVERLAPPING ADJACENT DIGITS AND ACROSS SURFACES.

7

WE ALSO NOTICED A MILD LOSS OF DIFFERENTIATION OF THE

8

DIGITS ON THE UNTRAINED SIDE.

9

BOTH WAS THE ENLARGEMENT OF THESE CUTANEOUS RECEPTIVE

10

FIELDS THAT SERIOUSLY OVERLAP THE ADJACENT DIGITS AND

11

THE GLABROUS AND THE DORSAL SURFACES.

12

PRIMATES LOST THE ABILITY TO CONTINUE TO PERFORM THE

13

TARGET TASK, ALL OTHER HAND MOVEMENTS WERE ENTIRELY

14

NORMAL.

15

WE DOCUMENTED

THERE WAS A LOSS OF

THERE WAS A REDUCTION IN THE AREA OF THE

WHAT WAS CONSISTENT ON

ALTHOUGH THESE

IN ANIMALS WITH DYSTONIA, THE NEURONAL

16

REPRESENTATION OF A SINGLE DIGIT PERSISTED ACROSS LARGE

17

CORTICAL DISTANCES, UP TO 1600 MICRONS; WHEREAS, IN A

18

NORMAL NONTRAINED PRIMATE, THE NEURONAL REPRESENTATION

19

OF A DIGIT CHANGES APPROXIMATELY EVERY HUNDRED MICRONS.

20

AND YOU CAN SEE THAT IN BOTH OF THESE PLOTS.

21

IN ONE ANIMAL WE WERE ABLE TO IMPLANT AN

22

ELECTRODE OVER THE DIGITS D 1 AND D 2 BEFORE WE BEGAN

23

THE TRAINING.

24

OF DIGIT 1 AND DIGIT 2.

25

DYSTONIA, WE NOTICED THAT THE SIZE OF RECEPTIVE FIELDS

WE WERE CLEARLY LOCATED OVER THE AREAS WITH THE ONSET OF THE

9

1

INCREASED PROPORTIONAL TO THE TRAINING TIME, WHICH YOU

2

CAN SEE ON THE LEFT.

3

AS THE DYSTONIA PROGRESSED, THE AREA OF THE

4

REPRESENTATION OF THE DIGITS 1 AND 2 WHICH HAD BEEN

5

CAREFULLY PLOTTED WITH THE ELECTRODE WERE ESSENTIALLY

6

REPLACED WITH THE EXPANSION OF THE WHISKER INTO THE

7

AREA OF THE REPRESENTATION OF DIGITS.

8

WAS NO LONGER OVER THE AREA OF D 1 AND D 2 AS THAT AREA

9

WAS BECOMING SMALLER IN SIZE AND THE ADJACENT AREA

10 11

THE OTHER INTERESTING THING WAS

SO THE ELECTRODE

EXPANDING IN SIZE. IN ONE CLINICAL STUDY WE ALSO REPORTED

12

DECREASED SENSORY DISCRIMINATION IN PATIENTS WITH HAND

13

DYSTONIA AND A SIMILAR LOSS OF DIGITAL DIFFERENTIATION

14

AS MEASURED BY MAGNETIC RESONANCE IMAGING; IN OTHER

15

WORDS, LOOKING AT THE SENSORY AND MOTOR EVOKED

16

RESPONSES.

17

HERE IN THIS SLIDE YOU CAN SEE WHAT A NORMAL

18

EVOKED RESPONSE WOULD BE FOR THE MOTOR CORTEX, THE

19

MOTOR EVOKED FIELD, THE SENSORIMOTOR EVOKED FIELD, AND

20

THE SENSORY EVOKED FIELD.

21

IS A NICE CLEAR ORGANIZATION THAT IS CONSISTENT ACROSS

22

SENSORY AND MOTOR STIMULI.

23

AND YOU CAN SEE THAT THERE

IN THE PATIENTS WITH DYSTONIA, WE FOUND A

24

DISTINCTION BETWEEN THOSE WHO ARE SEVERE DYSTONIA AND

25

THOSE WHO ARE MILD DYSTONIA.

10

THE AMPLITUDE WAS

1

SIGNIFICANTLY HIGHER FOR PATIENTS WITH SEVERE DYSTONIA

2

ON THE AFFECTED AND UNAFFECTED SIDES; BUT FOR THOSE

3

WITH MILD DYSTONIA, THE AMPLITUDE WAS REDUCED COMPARED

4

TO NORMALS.

5

AMPLITUDE WAS, AGAIN, SIGNIFICANTLY LOWER FOR PATIENTS

6

WITH MILD DYSTONIA COMPARED TO CONTROLS AND

7

SIGNIFICANTLY HIGHER FOR THOSE WITH SEVERE DYSTONIA.

8 9

ON THE SENSORY EVOKED POTENTIALS, THE

AND IN THESE REPRESENTATIONS YOU CAN SEE THAT THERE IS A REDUCTION IN THE AMPLITUDE IN PATIENTS WITH

10

MILD DYSTONIA BOTH FOR THE MOTOR EVOKED FIELDS, THE

11

SENSORIMOTOR EVOKED FIELDS, AND THE SENSORY EVOKED

12

RESPONSES.

13

SEVERE DYSTONIA, THE AMPLITUDE IS UNUSUALLY LARGE

14

COMPARED TO CONTROLS.

15

YOU ALSO NOTICE IN THE SEVERE PATIENTS WITH

IN ADDITION, FOLLOWING THE STIMULATION, THERE

16

WAS A SPREAD OF ACTIVATION OF STIMULI INDUCED ACROSS A

17

LARGER AREA ON BOTH THE AFFECTED AND UNAFFECTED SIDE,

18

AND THE CORTICAL REPRESENTATION OR ACTIVATION WAS ALSO

19

LARGER COMPARED TO CONTROLS.

20

THE ARGUMENT TODAY, HOWEVER, IS IN THE

21

PATIENTS WITH DYSTONIA VERSUS THE ANIMALS WHERE WE

22

INDUCE THE DYSTONIA, ARE THE CHANGES IN THE CORTEX

23

REALLY A CAUSE OR EFFECT OF THE MOTOR MOVEMENT

24

DYSFUNCTION?

25

THAT THE CORTICAL CHANGES ARE A CONSEQUENCE OF

IN OUR ANIMAL STUDIES WE FEEL CONFIDENT

11

1

TRAINING, AND THAT THEY ACTUALLY CHANGE AND SPREAD WITH

2

INCREASED SEVERITY AND DURATION OF DYSFUNCTION.

3

OTHER HAND, WE DON'T MAP AND WE DON'T TEST PATIENTS WHO

4

DON'T HAVE DYSTONIA PRIOR TO THE DEVELOPMENT OF THESE

5

ABNORMAL SOMATOSENSORY CHANGES, AND WE BELIEVE THE

6

BILATERAL REPRESENTATION AND CHANGES PROBABLY REPRESENT

7

AN INTERACTION OF GENETICS OR RISKS FOR DYSTONIA AS

8

WELL AS REPETITIVE PRACTICE.

ON THE

WHAT IS FASCINATING ABOUT THIS DISORDER OF

9 10

FOCAL HAND DYSTONIA IS THAT THERE IS NO SPONTANEOUS

11

RECOVERY.

12

STOPS PERFORMING THE TARGET TASK, THE DYSTONIA DOES NOT

13

DISAPPEAR.

14

YEARS LATER SAT DOWN AT THE PIANO, HAD NOT PLAYED THE

15

PIANO FOR 20 YEARS, THE DYSTONIA WAS STILL PRESENT.

16

THE TASK-SPECIFIC DYSTONIA HAS ONLY ONE OPTION, AND

17

THAT IS TO RETRAIN THE BRAIN.

18

IF A PATIENT WITH FOCAL DYSTONIA SIMPLY

I'VE SEEN A PATIENT WHO IS A PIANIST WHO 20

PATIENTS WITH GENERALIZED DYSTONIA ARE VERY

19

DIFFICULT TO TREAT, AND TODAY THEY ACTUALLY IMPLANT

20

STIMULATORS IN THE GLOBUS PALLIDUS, AND COMBINING THE

21

STIMULATION WITH TRAINING, PARTICULARLY LEARNING-BASED

22

TRAINING, THESE PATIENTS CAN LIVE A FUNCTIONAL LIFE.

23

NEUROLOGISTS TELL THE PATIENTS THAT THERE

24

REALLY IS NO CURE FOR FOCAL HAND DYSTONIA, BUT WITH

25

APPROPRIATE INJECTIONS OF BOTULINUM TOXIN TO INTERFERE

12

1

WITH THE TRANSMISSION OF THE IMPULSE TO THE MUSCLE, AND

2

WITH TRAINING, PARTICULARLY LEARNING-BASED TRAINING,

3

THE SIGNS AND SYMPTOMS OF DYSTONIA CAN BE MANAGED.

4

FOCAL DYSTONIA IS AN INVOLUNTARY -- IF FOCAL

5

HAND DYSTONIA IS AN INVOLUNTARY DISORDER OF MOVEMENT

6

CONSEQUENT TO ABERRANT LEARNING, THEN MOTIVATED

7

INDIVIDUALS SHOULD BE ABLE TO RESTORE NORMAL MOTOR

8

SKILLS BY RETRAINING THE BRAIN, PARTICULARLY FOLLOWING

9

THE PRINCIPLES OF NEUROPLASTICITY AND INTEGRATING

10 11

SENSORY, SENSORIMOTOR, AND MOTOR PARADIGMS. WHAT IS IMPORTANT ABOUT LEARNING-BASED

12

TRAINING IS THAT YOU HAVE TO SET A STRONG FOUNDATION

13

FOR LEARNING TO TAKE PLACE.

14

FOUNDATION OF LEARNING MUST BE BASED ON FITNESS AND

15

WELLNESS, INCLUDING ATTENTION TO PHYSICAL CONDITIONING,

16

FLEXIBILITY, STRENGTHEN ENDURANCE, AS WELL AS GOOD

17

BIOMECHANICS, APPROPRIATE ADJUSTMENTS AND MANAGEMENT OF

18

SOCIAL CHALLENGES, PSYCHOLOGICAL DIFFERENCES,

19

NUTRITIONAL STATUS, AND PARTICULARLY STRESS MANAGEMENT.

20

THAT MEANS THAT THE

IT IS ALSO IMPORTANT FOR PATIENTS TO BECOME

21

AWARE OF HOW TO USE THEIR LIMBS IN A STRESS FREE WAY

22

THAT USES NORMAL MOVEMENTS, GOOD BIOMECHANICS, AND GOOD

23

POSTURE, EMPHASIZING THE USE OF THE INTRINSIC MUSCLES

24

OF THE HANDS WITH PROXIMAL CONTROL FROM THE SHOULDER

25

AND STRONG ATTENTION TO SENSORY INFORMATION TO GUIDE

13

1

THE MOVEMENT RATHER THAN OVERPOWER THE MOVEMENT WITH

2

HIGH LEVELS OF REPETITION AND UNNECESSARY ALTERNATING

3

MOVEMENTS.

4

APPLYING THE PRINCIPLES OF BASIC SCIENCE TO

5

CLINICAL LEARNING-BASED TRAINING, IT APPEARS THAT THE

6

BEHAVIORS THAT ARE TRAINED MUST REQUIRE ATTENTION,

7

REPETITION, POSITIVE FEEDBACK, NONSTEREOTYPICAL

8

MOVEMENTS, STIMULI DELIVERED SEPARATELY IN TIME,

9

PROGRESSION OF DIFFICULTY OF TASK PERFORMANCE, AND

10 11

PRACTICE SPACED OVER TIME. THE RESEARCH IN NEUROSCIENCE ALSO SUPPORTS

12

THAT OTHER THINGS CAN REINFORCE LEARNING.

FIRST OF

13

ALL, LEARNING SHOULD BE FUN.

14

PEOPLE WON'T DO IT.

15

TRAINING, YOU MUST GET CONSENSUS OF THE PATIENT, THE

16

FAMILY, AND THE PHYSICIAN ABOUT THE GOALS OF TREATMENT.

17

IT IS ALSO ESSENTIAL TO EDUCATE THE PATIENT AND THE

18

FAMILY ABOUT WHAT WE KNOW TODAY ABOUT NEUROPLASTICITY.

19

IT IS ABSOLUTELY ESSENTIAL TO STOP THE ABNORMAL

20

MOVEMENTS BECAUSE IF THEY CONTINUE TO BE REPEATED, THEN

21

THE ABERRANT LEARNING CONTINUES.

22

QUALITY NORMAL MOVEMENTS, IMAGE SUCCESS, BEING

23

CONFIDENT, HAVING HIGH SELF-ESTEEM, AND BEING ABLE TO

24

IMAGE THE POSSIBILITY OF RESTORING NORMAL MOVEMENT IS

25

CRITICAL TO SUCCESSFUL LEARNING.

AND WHEN IT ISN'T FUN,

BEFORE YOU BEGIN LEARNING-BASED

14

WE MUST REINFORCE

COMPLYING WITH THE

1

PRACTICE NECESSARY, THE SCHEDULE, AND PERSEVERING WITH

2

TRAINING OVER TIME IS ESSENTIAL. WE ALSO KNOW WE CAN REINFORCE LEARNING BASED

3 4

ON RESEARCH, THAT IF WE TRAIN BOTH HEMISPHERES, WE KNOW

5

THAT THE CONTRALATERAL HEMISPHERE IS EXCITORY TO THE

6

INVOLVED LIMB WHERE THE PATHWAYS ON THE IPSILATERAL

7

SIDE TEND TO BE INHIBITORY.

8

ENHANCED BY ADDING AN ELEMENT OF SURPRISE OR EVEN A

9

PRELIMINARY PRETRAINING EXPOSURE TO WHAT IS EXPECTED AS

LEARNING CAN ALSO BE

10

IN A SUBLIMINAL STIMULUS.

11

MUST BE PROGRESSED IN DIFFICULTY, BUT THE AMOUNT OF

12

PROGRESSION MUST BE CAREFULLY STAGED SO NOT TO EXCEED

13

THE CAPACITY OF THE NERVOUS SYSTEM FOR CHANGE.

14

ALSO IMPORTANT TO INCREASE THE FUNCTIONAL TOPOGRAPHY OF

15

THE HAND AND NOT JUST THE ANATOMICAL SENSORY AND MOTOR

16

REPRESENTATION.

17

MAGNIFY THE FUNCTIONAL TOPOGRAPHY BY PERFORMING THE

18

SAME TASK WITH AN ALTERNATIVE LIMB, SUCH AS LEARNING TO

19

WRITE WITH YOUR FOOT IF YOU HAVE A DYSTONIA FOR

20

WRITING.

21

WE ALSO KNOW THAT TRAINING

IT'S

AND IT HAS BEEN SHOWN THAT YOU CAN

HERE IS AN EXAMPLE OF USING DIFFERENT

22

POSITIONS TO PLACE PEOPLE IN TO PERFORM A TARGET TASK.

23

IN ORDER TO REALLY INHIBIT THE DYSTONIA, YOU WANT TO

24

PUT PEOPLE IN A POSITION WHERE THEY CAN FUNCTION

25

WITHOUT THE DYSTONIC MOVEMENTS.

15

THIS HAPPENS TO BE A

1

MOVIE, AND I HAVE NO WAY OF ACTIVATING IT FROM THE

2

PLATFORM HERE. OKAY.

3

THE PRINCIPLES OF LEARNING-BASED

4

TRAINING ARE IMPORTANT IF I APPLY THEM SPECIFICALLY TO

5

SENSORIMOTOR TRAINING.

6

THE GUIDELINES I'VE ALREADY MENTIONED; BUT WHEN YOU

7

MOVE TOWARD SENSORIMOTOR RETRAINING, THIS REQUIRES ONE

8

TO THINK ABOUT SENSORY, THE INPUTS AND THE FEEDBACK,

9

RATHER THAN THINKING ABOUT MOTOR.

SO, IN GENERAL, YOU FOLLOW ALL

THE LEARNING WOULD

10

TAKE CARE IN PARADIGMS WHICH WERE TAKING A LOT OF

11

INFORMATION FROM CUTANEOUS AND JOINT PROPRIACEPTIVE

12

FEEDBACK, MINIMIZING VISUAL CUES.

13

SENSORY MODALITIES TENDS TO HELP GENERALIZE LEARNING,

14

INCLUDING ACTIVE AND PASSIVE STIMULI SEEMS TO BE

15

CRITICAL.

16

DECISION ABOUT A PARTICULAR SENSORY OR SENSORIMOTOR

17

EXPERIENCE, AND IT MUST BE IMPORTANT TO EMPHASIZE

18

INTEGRATING SENSORY PROCESSING INTO ALL FUNCTIONAL

19

ACTIVITIES.

20

USING A VARIETY OF

INDIVIDUALS MUST BE FORCED TO MAKE A

I BELIEVE THERE ARE FIVE PHASES AND PROBABLY

21

MORE TO BEGIN A PROGRESSIVE LEARNING-BASED TRAINING

22

PROGRAM IN SENSORIMOTOR LEARNING.

23

JUST TO BE ABLE TO IMAGINE THAT YOUR HAND IS NORMAL.

24

THE SECOND PHASE IS TO IMPROVE SENSORY DISCRIMINATION.

25

THE THIRD PHASE IS TO PERFORM AND CONCENTRATE ON

16

THE FIRST PHASE IS

1

DEVELOPING GRADED CONTROLLED MOVEMENTS.

2

PHASE IS TO WORK ON SENSORY MOTOR SKILLS, AND THE LAST

3

PHASE IS TO RESTORE FINE MOTOR CONTROL WITHOUT TREMORS

4

OR ABNORMAL MOVEMENT FIRST AT THE NONTARGET AND THEN

5

FINALLY AT THE TARGET TASK.

6

THE FOURTH

THE GOAL OF BEING ABLE TO IMAGINE USING YOUR

7

HANDS NORMALLY IS THE FIRST PLACE TO START.

THERE ARE

8

A SERIES OF PICTURES THAT YOU COULD LOOK AT OF THE

9

HANDS AND THE GOALS TO LOOK AT THOSE PICTURES WITHOUT

10

FEELING THE ABNORMAL MOVEMENT OR IN SOME CASES FEELING

11

ANY PAIN.

12

AND DECIDE IF IT'S A RIGHT OR LEFT HAND, AGAIN, WITHOUT

13

ANY ABNORMAL MOVEMENT.

14

THE POSITION OF THE HAND.

15

WOULD BEGIN TO IMITATE THOSE POSITIONS, AND, FINALLY,

16

YOU WOULD COPY THOSE POSITIONS.

17

VIDEO OF SOMEONE ELSE PERFORMING THE TASK AND IMAGINE

18

IT'S YOUR HAND.

19

YOU SHOULD BE ABLE TO LOOK AT THOSE PICTURES

YOU SHOULD BE ABLE TO VISUALIZE THEN USING A MIRROR, YOU

YOU COULD ALSO WATCH A

WE HAVE A SERIES OF NEAR 360 DIFFERENT

20

PICTURES FOR PATIENTS TO LOOK AT AND MAKE THE JUDGMENT

21

OF RIGHT OR LEFT AND BEGIN TO IMAGINE GETTING INTO

22

THESE POSITIONS, AND THIS IS JUST AN EXAMPLE.

23

THE GOAL OF THE SECOND PHASE OF TRAINING IN

24

SENSORY DISCRIMINATION IS TO REDIFFERENTIATE THE TOP

25

GRAPHICAL REPRESENTATION BY IMPROVING THE PRECISION AND

17

1

THE ACCURACY OF SENSORY DISCRIMINATION, PARTICULARLY

2

USING CUTANEOUS AND HAPTIC TASKS TO TARGET THE

3

REDIFFERENTIATION.

4

THIS IS AN EXAMPLE OF A SENSORY TASK THAT IS

5

CONCENTRATING ON CUTANEOUS RECEPTORS WHERE SOMEONE IS

6

DRAWING DIFFERENT TYPES OF DESIGNS AND FIGURES IN WHICH

7

THE PATIENT HAS TO REPRODUCE EITHER BY DRAWING THEM ON

8

THEIR OWN HAND IN THE SAME PLACE IN THE SAME SIZE OR

9

REPRODUCING THEM ON A PIECE OF PAPER.

THE DESIGNS GET

10

HARDER, AND THE SIZE OF THE STIMULUS GETS SMALLER.

11

HERE IS AN EXAMPLE OF HAPTIC TRAINING OR

12

STEREOGNOSIS.

THAT IS FEELING AND MATCHING OBJECTS,

13

LEARNING TO READ BRAILLE, MATCHING BUTTONS THAT ARE THE

14

SAME, AND BEGINNING TO SORT BY SIZE AND BY SURFACE

15

COARSENESS ON DIFFERENT OBJECTS.

16

IT'S ALSO NECESSARY TO MOVE TO THIS PHASE III

17

AS SOON AS POSSIBLE IN ORDER TO LEARN TO LIGHTLY HANDLE

18

AND MOVE OBJECTS WHILE KEEPING THE HAND IN A NORMAL

19

FUNCTIONAL POSITION.

20

THE TREADMILL BELT WORKING UNDERNEATH THEIR HAND WHILE

21

THEY'RE TRYING TO DO THE TARGET TASK.

22

PLASTIC FAN AND TOUCHING THE PLASTIC BLADES WITHOUT

23

STOPPING THE FAN OR PLACING YOUR HAND ON A SCALE AND

24

MAINTAINING THAT WEIGHT FOR CERTAIN PERIOD OF TIME IN

25

ORDER TO CONTROL AND NOT BE TOO HARD OR TOO SOFT ON THE

AND HERE YOU CAN SEE SOMEONE HAS

18

SOMEONE TAKING A

1

SCALE.

2

PHASE IV IS THE SENSORIMOTOR SKILL

3

RETRAINING, AND THE GOAL IS TO IMPROVE THE REGULATION,

4

THE QUANTITY, THE QUALITY, AND THE ACCURACY OF

5

SENSORIMOTOR SKILLS TO REPRODUCE THE NORMAL MOVEMENTS.

6

THE GOAL IS TO LET THE SENSATION OF THE OBJECT CONTROL

7

AND GUIDE THE HAND.

8

IN SENSORIMOTOR TRAINING IS TO PLAY GAMES THAT ARE

9

BASED ALL ON SENSORY INPUTS AND SENSORY FEEDBACK.

ONE OF THE GREATEST THINGS TO DO

THIS

10

WOULD INCLUDE PLAYING GAMES WITH YOUR EYES CLOSED WITH

11

OTHER PEOPLE SO YOU STIMULATE AN ELEMENT OF

12

COMPETITION.

13

PLAY YATZE AND SCRABBLE WITH BRAILLE CARDS, AND THAT IS

14

EVEN MORE CHALLENGING.

15

YOU CAN PLAY BLACKJACK AND YOU CAN ALSO

AS WE PROGRESS IN SOME OF THE SENSORIMOTOR

16

TASKS, THIS IS USING THE BRAILLE CARDS, YOU CAN USE

17

MIRRORS TO GIVE POSITIVE FEEDBACK BY PUTTING THE

18

UNAFFECTED SIDE IN FRONT OF THE MIRROR AND THE AFFECTED

19

SIDE BEHIND THE MIRROR.

20

ACTUALLY LOOKS LIKE THE MIRROR IMAGE, AND NOW YOU GET

21

POSITIVE FEEDBACK THAT YOUR HAND IS MOVING NORMALLY.

22

WITH THIS MIRROR IMAGE YOU CAN PRACTICE BOTH SENSORY

23

TASKS AS WELL AS MOTOR TASKS.

24 25

THEN YOUR AFFECTED SIDE

HERE IS ANOTHER EXAMPLE OF SENSORIMOTOR SKILL TRAINING WHERE THERE ARE BEANS AND THERE ARE QUARTERS

19

1

AND NICKELS AND DIMES IN THE BUCKET, AND THE PATIENT

2

HAS TO GO IN AND FIND SAY TEN QUARTERS AND NOTE THE

3

SPEED OF WHICH IT TAKES THEM TO FIND THE QUARTERS AND

4

TRY TO CONTINUE TO IMPROVE THAT SPEED.

5

FEEL LETTERS AND SPELL WORDS.

6

WITH YOUR EYES CLOSED AND MATCH THE PUZZLE WITH THE

7

PIECES OF PUZZLE BEHIND A BARRIER SO YOU DON'T SEE THE

8

PIECES, BUT YOU FEEL THE PIECES.

9

YOU CAN ALSO

YOU CAN ASSEMBLE PUZZLES

IN THE LAST PHASE THE FINE MOTOR CONTROL

10

PHASE, THE GOAL IS TO IMPROVE FINE MOTOR CONTROL ON THE

11

TARGET TASK.

12

ON A NONTARGET TASK, PARTICULARLY IN DIFFERENT BODY

13

POSITIONS, IN DIFFERENT CHALLENGING ENVIRONMENTS WITH

14

DIFFERENT SENSORY INTERFACES.

THE GOAL IS NOT TO

15

INDUCE THE ABNORMAL MOVEMENT.

AND HERE I SHOW A

16

PICTURE OF A TREADMILL WHERE WE ACTUALLY OFTEN BEGIN TO

17

HAVE PEOPLE WORK ON WRITING RETRAINING WHILE THEY'RE

18

WALKING ON THE TREADMILL WITH THEIR EYES CLOSED.

19

HOWEVER, FOR THE MOST PART YOU MUST START

WHEN YOU TRAIN ON THE TARGET TASK, IT'S

20

IMPORTANT TO USE A LOT OF SENSORY FEEDBACK OR GET THEM

21

IN THESE UNUSUAL POSTURES, MAYBE EVEN PROVIDE TEMPORARY

22

STABILIZATION WITH A SPLINT AS NEEDED TO PREVENT

23

ABNORMAL MOVEMENTS.

24

FROM PROXIMAL CONTROL VERSUS DISTAL MOVEMENTS IS A HARD

25

TASK TO CHANGE, BUT YOU CAN DO THIS WHEN THE BACKGROUND

THE CHANGE IN PARADIGM OF MOVING

20

1

IS ALTERED.

2

HERE IS A CASE OF A PATIENT WITH A FOCAL HAND

3

DYSTONIA ON A KEYBOARD.

4

DYSTONIA.

5

CONSIDER A NONTARGET TASK, AND THAT IS SIMULATING A

6

STEERING WHEEL IN A CAR.

7

WALKING ON A TREADMILL WITH HIS EYES CLOSED TRYING TO

8

TURN THIS SIMULATED STEERING WHEEL WITH KEEPING HIS

9

HAND IN ABSOLUTELY NORMAL POSITION.

10

HE HAS A KEYBOARDER'S

AND NOW HE'S WORKING ON WHAT HE WOULD

AND HE IS AT THIS POINT

HERE'S ANOTHER EXAMPLE OF WORKING ON FINE

11

MOTOR CONTROL IN AN UNUSUAL ENVIRONMENT.

12

CASE IT IS USING SHAVING CREAM SO THAT THEY ARE

13

LEARNING TO WRITE.

14

WRITTEN ON THE PAPER IN FRONT OF THEM.

15

THEIR WRITING SMALLER AND SMALLER, BUT THEY'RE GETTING

16

A LOT OF SENSORY FEEDBACK BECAUSE OF THE SHAVING CREAM.

17

AND IN THIS

THEY WRITE MESSAGES THAT I HAVE THEY THEN GET

HERE'S AN EXAMPLE OF FINE MOTOR PRACTICE

18

TRYING TO RESHAPE THE USE OF THE HAND.

19

PARTICULAR CASE WE'RE TRYING TO MAKE BOTH THE DYSTONIC

20

HAND AND THE UNAFFECTED HAND LOOK ALIKE, BOTH LOOK

21

ALIKE IN A FUNCTIONAL TASK AS WELL AS LOOK ALIKE WHEN

22

THE HAND IS SIMPLY OPEN AND THE PALM IS UP.

23

WILL NOTICE HE HAS A SMALL SPLINT ON THE METACARPAL

24

PHALANGEAL JOINT OF THE FIFTH DIGIT, TRYING TO PREVENT

25

THE EXPRESSION OF ANY ABNORMAL DYSTONIC MOVEMENTS.

21

IN THIS

AND YOU

1

HERE IS A CASE OF USING BIOFEEDBACK TO TRY TO

2

IMPROVE KEYBOARDING CONTROL AND STOP ALL OF THE

3

ABNORMAL MOVEMENT ON THE KEYBOARD.

4

ACTUALLY AN AUDITORY FEEDBACK, AND THE ELECTRODE IS

5

PLACED EITHER ON THE MUSCLES THAT YOU WANT TO EXCITE OR

6

THE MUSCLES THAT YOU WANT TO QUIET.

7

HAND, THE HALF-SHAPE BALL, IS TO KEEP THE HAND SHAPED

8

IN A FUNCTIONAL POSITION.

9

IMPROVE THE POSTURE.

AND THE FEEDBACK IS

THE BALL IN THE

THE LUMBAR ROLL IS TO

AND THESE TRAINING DEVICES ARE

10

ONLY A WAY TO MOVE PEOPLE FORWARD ON THE TARGET TASK.

11

IT'S ALSO IMPORTANT TO WORK ON FINE MOTOR SKILL

12

DEVELOPMENT AT TARGET TASKS WITH THE ALTERNATIVE TYPES

13

OF DEVICES.

14

SO HERE IS A KEYBOARD, THE DEVORE KEYBOARD,

15

WHERE YOU CAN'T ACTUALLY USE TOUCH TYPING.

16

YOU SEE A PATIENT PRACTICING WRITING, PICKING UP A PEN

17

AND PUTTING IT DOWN, USING THE MIRROR, AND THEN

18

BEGINNING TO WRITE USING THE MIRROR AND USING THE IMAGE

19

OF THE UNAFFECTED SIDE TO GUIDE THE DYSTONIC HAND.

20

AND THEN

HERE IS AN EXAMPLE OF USING A SIMULATED

21

INSTRUMENT TO TRY TO GET BACK TO PLAYING THE TARGET

22

INSTRUMENT.

23

DRUM PAD INSTEAD OF A DRUM, AND YOU CAN SEE IN THE

24

DRUMMER THERE IS BIOFEEDBACK THAT'S PLACED ON THE ARM

25

TO TRY TO GIVE HIM FEEDBACK ABOUT WHETHER HE'S DOING

USING A DOWEL INSTEAD OF A FLUTE, USING A

22

1 2

THE TASK PROPERLY. IT IS ALSO POSSIBLE TO USE MIRROR FEEDBACK TO

3

RETRAIN FACIAL DYSTONIA.

4

A 90-DEGREE ANGLE, YOU TAKE THE SIDE OF THE FACE THAT

5

IS DYSFUNCTIONAL AND THEY GET THE IMAGE OF THE

6

FUNCTIONAL SIDES OF THE FACE, AND NOW THEY CAN PRACTICE

7

NORMAL MOVEMENTS OF THE MUSCLES OF THE FACE AND GET THE

8

FEEDBACK THAT THEIR FACE LOOKS NORMAL.

9

BY PUTTING THE TWO MIRRORS AT

AT THIS TIME WE HAVE DONE SEVERAL CASE

10

STUDIES AND SEVERAL EXPERIMENTAL STUDIES DEMONSTRATING

11

THAT LEARNING-BASED SENSORIMOTOR TRAINING CAN BE

12

EFFECTIVE WITH APPROXIMATELY 95 PERCENT OF THOSE WHO

13

ACTUALLY COMPLY WITH THE PROGRAM.

14

WILL MAKE SOMEWHERE BETWEEN 75 TO 90 PERCENT

15

IMPROVEMENT AS MEASURED BY CLINICAL PERFORMANCE

16

VARIABLES AND MAGNETIC SOURCE IMAGING.

17

DO RETURN TO WORK, ONLY 50 PERCENT OF THE MUSICIANS

18

HAVE BEEN ABLE TO RETURN TO FUNCTIONAL AND PROFESSIONAL

19

PERFORMANCE.

THOSE WHO COMPLY

WHILE 8 PERCENT

20

WHAT IS CRITICAL ABOUT THOSE WHO GET BETTER

21

IS THE FACT THAT THEY'VE HAD POSITIVE EXPECTATIONS TO

22

IMPROVE, THEY HAVE BEEN WILLING TO PRACTICE, MENTAL

23

PRACTICE AND NOT ALL PHYSICAL PRACTICE, THEY COMPLY

24

WITH THE REPETITIVE TRAINING STRATEGY, THEY CAN CHANGE

25

THEIR TECHNIQUES, AND THEY CAN ACTUALLY STOP THE

23

1

ABERRANT NORMAL MOVEMENTS.

ALTHOUGH INTERVENTION WAS

2

TARGETED TO IMPROVE THE UPPER LIMB IN PATIENTS WITH

3

FOCAL HAND DYSTONIA, SIMILAR STRATEGIES HAVE BEEN

4

APPLIED WITH PATIENTS WITH CERVICAL DYSTONIA ALSO WHO

5

REPORT, NOT ONLY IMPROVEMENT IN THE CERVICAL DYSTONIA,

6

BUT IMPROVEMENT IN THEIR SPEECH AND THEIR ARTICULATION

7

AND THEIR LANGUAGE.

8

WE ARE CURRENTLY INVOLVED IN A RANDOMIZED

9

CLINICAL TRIAL WITH A SMALL NUMBER OF PATIENTS WITH

10

FOCAL HAND DYSTONIA, AND THEY'RE DOING TWO TYPES OF

11

LEARNING-BASED TRAINING.

12

TRAINING, WHICH IS BASED ON A BRAIN FITNESS PARADIGM,

13

AND THE OTHER IS LEARNING-BASED SENSORIMOTOR TRAINING.

14

ONE IS GENERAL MEMORY-BASED

THESE PATIENTS WILL BE RANDOMLY ASSIGNED TO

15

ONE OF TWO GROUPS.

16

SENSORIMOTOR TRAINING.

17

TWO WEEKS OF LEARNING-BASED SENSORIMOTOR TRAINING, AND

18

THE OTHER DID ALL THE LEARNING-BASED SENSORIMOTOR

19

TRAINING AT HOME.

20

THEM HOW TO DO THE TRAINING, ALL HAD HANDBOOKS,

21

EVERYTHING WAS IN WRITING, AND ALL WERE TO REPORT THE

22

AMOUNT OF TIME THEY WERE COMPLYING WITH THE PROGRAM.

23

THEY BOTH DO BRAIN FITNESS AND ONE CAME IN FOR AN INTENSIVE

ALL HAD VIDEOTAPES TO REALLY REMIND

THE PRELIMINARY ANALYSIS OF THOSE COMPLETING

24

THE PROGRAM DEMONSTRATES THE CHALLENGE OF COMPLIANCE.

25

AND WHILE I RECOGNIZE THE NEUROPHYSIOLOGY OF LEARNING,

24

1

I THINK WE UNDERSTAND THE DECODING PROCESS.

2

PATIENTS DON'T COMPLY WITH THE REPETITIONS AND THE

3

CODING AND THE DECODING, I CAN TELL YOU THERE IS NO

4

LEARNING.

5

IF

THOSE WHO ARE COMPLYING WITH BOTH THE

6

PRACTICE PROGRAM FOR THE BRAIN FITNESS PROGRAM, WHICH

7

IS BASED ON MEMORY, AND THOSE CONCENTRATING AND

8

COMPLETING THE PROGRAM ON LEARNING-BASED SENSORIMOTOR

9

TRAINING APPEAR TO BE MAKING THE GREATEST GAINS.

10

AND YOU CAN SEE ON JUST THIS BRIEF SUBJECTIVE

11

OUTLINE HERE THAT THOSE WHO ARE DOING THE BRAIN FITNESS

12

TRAINING AT THE SAME TIME THEY'RE DOING THE

13

LEARNING-BASED TRAINING AND THEY'RE COMPLYING WITH THE

14

PROGRAMS LOOK LIKE THEY'RE HAVING THE BEST OUTCOME.

15

SO IS LEARNING-BASED SENSORIMOTOR TRAINING

16

EFFECTIVE?

WE HAVE ALSO REPORTED A SIMILAR STRATEGY

17

USED WITH PATIENTS STABLE POST STROKE.

18

DEMONSTRATED THAT THESE PATIENTS CAN IMPROVE

19

SENSORIMOTOR FUNCTION EVEN THOUGH THEY MIGHT BE ONE TO

20

FIVE YEARS POST STROKE.

21

INTENSIVE TRAINING IS ASSOCIATED WITH THE GREATEST

22

IMPROVEMENT.

23

WEEKS WERE ABLE TO MAKE 50 PERCENT GAINS IN FUNCTIONAL

24

ABILITIES COMPARED TO THOSE TRAINING ONCE A WEEK FOR

25

SIX WEEKS.

WE HAVE

FURTHERMORE, THE MORE

WE FOUND PATIENTS TRAINING DAILY FOR SIX

25

1

SO, IN CONCLUSION, IT'S CLEAR FROM OUR

2

RESEARCH THAT IT IS POSSIBLE TO APPLY THE PRINCIPLES OF

3

BASIC NEUROSCIENCE AND PLASTICITY TO CLINICAL PRACTICE,

4

BUT COMPLIANCE, PATIENT COMPLIANCE, FAMILY SUPPORT IS

5

CRITICAL.

6

TO ACHIEVE ADEQUATE REPETITIONS TO GET THE CHANGE

7

REQUIRED IN THE BRAIN.

8

NORMAL REPETITIONS AND AVOIDING ABNORMAL MOVEMENTS, WE

9

HAVE A SERIOUS PROBLEM IN LEARNING.

IT IS PARTICULARLY CRITICAL IF YOU ARE GOING

WITHOUT THESE REPETITIONS OF

WE DEFINITELY NEED

10

TO DO MORE RESEARCH TO CLARIFY BOTH THE TYPE, THE

11

TIMING, AND THE INTENSITY OF BEHAVIORAL TRAINING NEEDED

12

TO MODIFY STRUCTURE.

13

REQUIRED 2,000 REPETITIONS A DAY AT A MINIMUM FIVE DAYS

14

A WEEK FOR AN AVERAGE OF 12 WEEKS TO DEVELOP THE

15

DYSTONIA.

16

FOR EXAMPLE, WE KNOW OUR ANIMALS

IT IS ALSO CLEAR FROM OUR RESEARCH THAT

17

CLINICAL-BASED TRAINING SHOULD BE COUPLED WITH

18

TECHNOLOGY, ROBOTICS, AND COMPUTERIZED TRAINING

19

PROGRAMS TO ASSURE COMPLIANCE, FUN, REWARD, AND

20

APPROPRIATE PROGRESSION OF TASK DIFFICULTY.

21

ADDITION, IT IS MY VIEW THAT THESE LEARNING-BASED

22

PROGRAMS SHOULD BE AVAILABLE IN COMMUNITY-BASED

23

SETTINGS AND NOT IN A HOSPITAL-BASED SETTING.

24

THOUGH THERE MAY NEED TO BE SOME SUPERVISION BY A

25

SKILLED REHABILITATION SPECIALIST, THE PATIENT NEEDS TO

26

IN

EVEN

1 2

BE PRIMARILY IN CHARGE OF THE REHAB. THUS, IT IS CRITICAL TO CREATE PARTNERSHIPS

3

BETWEEN CLINICIANS, BASIC SCIENTISTS, ENGINEERS, AND

4

PROGRAMMERS TO INNOVATE PARADIGMS OF TRAINING THAT ARE

5

BUILT ON THE PRINCIPLES OF NEUROPLASTICITY.

6

THERE ARE SOME LEARNING PROGRAMS THAT CLEARLY EXIST AND

7

ARE AVAILABLE TODAY, THERE ARE SOME ROBOTIC DEVICES

8

THAT ARE AVAILABLE FOR US TO USE IN THE CLINIC, AND

9

THERE ARE ALSO MACHINES THAT WILL HELP STEP THE LEG OF

WHILE

10

A PATIENT WHO HAS A PARALYSIS OF THE LEG, BUT MANY OF

11

THESE DEVICES ARE NOT SMART; THAT IS, THEY ARE NOT TIED

12

TO LEARNING-BASED TRAINING.

13

THAT ARE ORIENTED TOWARDS REPETITION, BUT NOT

14

LEARNING-BASED APPROACHES.

15

THEY'RE SIMPLY DEVICES

SO I GATHER FROM MY INABILITY TO USE MY

16

MOVIES THAT I CAN'T ACTUALLY SHOW YOU THE EXAMPLE OF

17

CASES AND HOW THEY'VE IMPROVED.

18

FOR QUESTIONS.

19

THE MODERATOR:

SO I WILL OPEN IT UP

THANK YOU VERY MUCH, DR. BYL,

20

FOR A FANTASTIC AND VERY STIMULATING PRESENTATION.

21

HAVE SOME QUESTIONS FOR YOU.

22 23 24 25

I

WHAT DO YOU THINK IS THE MAJOR LIMITATION IN MAXIMIZING THE PLASTICITY OF THE BRAIN? DR. BYL:

I OBVIOUSLY BELIEVE THAT MY

EXPERIENCE WORKING IN ANIMAL-BASED RESEARCH AND THEN

27

1

TRYING TO APPLY MY FINDINGS IN A MORE BASIC SCIENCE

2

LABORATORY TO THE CLINIC, MY FRUSTRATION IS PATIENT

3

COMPLIANCE.

4

METHODS TO CONTROL THEIR BEHAVIORS AND WE CAN CONTROL

5

THE AMOUNT OF TIME THEY DO THE REPETITIVE BEHAVIORS,

6

BUT IN THE REAL WORLD WITH REAL PATIENTS WHO ARE LIVING

7

IN REAL LIFE, IT IS VERY, VERY DIFFICULT TO GET THEM TO

8

COMMIT TO THESE LEARNING-BASED RETRAINING PARADIGMS

9

EVEN WHEN THEY PERFORM AND DO JOBS THAT DEMAND HIGH

10

LEVELS OF REPETITION THAT TOOK THEM TO THE POINT OF

11

SUCCESS TO BEGIN WITH.

12

DIFFICULT IT IS TO HAVE SOMEONE SPEND THE SAME AMOUNT

13

OF TIME RETRAINING THE BRAIN TO GET RID OF AN ABERRANT

14

MOVEMENT AS OPPOSED TO TRAINING TO BECOME A BETTER

15

PERFORMING ARTIST.

16 17 18

CLEARLY WHEN WE TRAIN ANIMALS, WE HAVE

THE MODERATOR:

IT'S AMAZING TO ME HOW

SO MAYBE WE NEED ANOTHER

PROSTHETIC DEVICE TO ENHANCE LEARNING. DR. BYL:

WHAT'S INTERESTING IS THAT THE

19

DEVICES I SAW THIS LAST WEEKEND AT A CONFERENCE I WAS

20

ATTENDING ALL HAVE THE POTENTIAL TO TAKE A PATIENT WITH

21

A STROKE WHO HAS NO MOVEMENT AND BEGIN TO PROVIDE SOME

22

PASSIVE AND THEN INTERACTIVE MOVEMENT; BUT, AGAIN, THEY

23

ARE NOT TIED TO LEARNING-BASED TRAINING PROGRAMS.

24

PATIENTS WOULD EASILY LOSE THEIR INTEREST IN JUST

25

HAVING THAT ACTIVITY.

28

SO

1

THE MODERATOR:

ANOTHER QUESTION.

WHAT IF

2

THERE IS A GENETIC ETIOLOGY THAT IS ULTIMATELY

3

IDENTIFIED FOR LOCAL HAND DYSTONIA?

4

LEARNING-BASED TRAINING STILL BE EFFECTIVE? DR. BYL:

5

COULD

THANKS FOR ASKING THAT QUESTION.

I

6

HAD A MOVIE TO SHOW YOU OF A PATIENT WHO WAS EXACTLY

7

THAT.

8

HAS A SERIOUS GENETIC CONTRIBUTION TO THAT DYSTONIA,

9

AND ESSENTIALLY THE LEARNING-BASED TRAINING PROGRAM WAS

A PATIENT WITH A GENERALIZED DYSTONIA, PROBABLY

10

RELATIVELY EFFECTIVE.

BUT GIVEN THE DEMANDS OF TAKING

11

CARE OF A YOUNG FOUR-YEAR-OLD, GIVEN THE DEMANDS OF

12

KEEPING THE HOUSE, GIVEN THE DEMANDS OF COMMUTING TO

13

COME AND SEE ME FOR LEARNING-BASED SENSORY TRAINING,

14

SHE MADE IMPROVEMENT, BUT NOT TO THE SAME DEGREE THAT

15

SHE WOULD HAVE MADE IMPROVEMENT WITH DEEP BRAIN

16

STIMULATORS IMPLANTED.

17

SO SHE HAD DEEP BRAIN STIMULATORS IMPLANTED,

18

AND THOSE ALONE WERE NOT ENOUGH TO CHANGE THE PARADIGM

19

OF HER DYSTONIA.

20

LEARNING-BASED TRAINING TO THE IMPLANTED ELECTRODES, IT

21

WAS ACTUALLY IMPORTANT TO SEE HOW MUCH IMPROVEMENT SHE

22

HAD IN MOTOR CONTROL.

23

SO, IN FACT, WHEN WE ADDED

THE MODERATOR:

SO IS ANYONE CURRENTLY

24

WORKING ON COMPUTERIZED TECHNOLOGY TO FACILITATE THIS

25

TYPE OF LEARNING?

29

1

DR. BYL:

I'VE BEEN WORKING WITH POSIT

2

SCIENCE IN SAN FRANCISCO, AND THEY HAVE THIS

3

LEARNING-BASED MEMORY PROGRAM FOR PATIENTS WITH

4

ALZHEIMER'S DISEASE.

5

FOR PATIENTS WITH LEARNING DISABILITIES.

6

THEY ARE WORKING ON A SMALL BUSINESS GRANT TO DEVELOP

7

SOME SENSORY INTERFACES THAT WE COULD USE FOR TRAINING

8

ABOUT PATIENTS WITH HAND DYSTONIA.

9

THAT THAT'S PART OF THE PROCESS.

AND IT'S BEEN APPLIED IN THE PAST AND, IN FACT,

SO IT IS MY VIEW

IT DOESN'T REALLY

10

ADDRESS THE PATIENTS WHO HAVE BALANCE DISORDERS AND

11

OTHER KINDS OF CONDITIONS THAT LEAD TO FALLING, BUT

12

CERTAINLY HAS THE POTENTIAL, I BELIEVE, TO BE

13

INTEGRATED INTO COMMUNITY-BASED FITNESS CENTERS.

14

INSTEAD OF JUST GETTING ON THE BIKE AND RIDING YOUR

15

BIKE, YOU OUGHT TO BE DOING A LEARNING-BASED TRAINING

16

PROGRAM, EITHER SOMETHING THAT'S SENSORIMOTOR IN NATURE

17

OR SOMETHING THAT'S LEARNING BASED IN TERMS OF MEMORY.

18 19 20 21 22

AND

YOU CAN GO AHEAD AND PLAY THAT WHILE I ANSWER QUESTIONS. THE MODERATOR:

THANK YOU.

OKAY.

SO WE'RE

READY TO PLAY SOME VIDEOS, THE MOVIES. DR. BYL:

HERE'S A PATIENT WHO ACTUALLY HAS A

23

PRETTY SEVERE HAND DYSTONIA, FOR THOSE OF YOU WHO

24

HAVEN'T SEEN IT.

25

THAT THE DYSTONIA IS WORSE WHEN SHE'S SITTING IN THE

AND WHAT I'M TRYING TO DEMONSTRATE IS

30

1

TARGET POSITION OF WHICH SHE USES THE COMPUTER.

WHEN

2

SHE CHANGES HER POSITION AND NOW JUST DROPS HER HAND ON

3

THE KEYBOARD WHEN SHE IS SUPINE, THAT ACTUALLY THE

4

AMOUNT OF DYSTONIC MOVEMENTS IS REDUCED. LET'S GO TO THE NEXT ONE AND CLICK ON THE ONE

5 6

ON THE BOTTOM TO THE LEFT, ON THE LEFT.

AND NOW YOU

7

CAN SEE THAT AFTER SHE WE WENT THROUGH SOME RETRAINING,

8

THAT SHE NOW IS ABLE TO USE HER HANDS ON THE COMPUTER

9

WITHOUT THE -- SHE'S IN A SITTING POSITION, BY THE WAY.

10

AND SHE IS NOW ABLE TO USE HER HANDS ON THE COMPUTER,

11

ALBEIT SLOWER, BUT MOVING FROM A PROXIMAL STRATEGY

12

RATHER THAN USING THE FLEXORS AND THE EXTENSORS OF THE

13

DIGITS. GO BACK ONE.

14

AND LET'S SHOW YOU THIS ONE SO

15

YOU CAN SEE THE SEVERITY OF THE DYSTONIA THAT CAN

16

OCCUR.

17

I WAS TALKING ABOUT.

18

HEALTHY, SHE HAS A VERY NICE FAMILY, AND SHE NOW IS

19

STRUGGLING TO OVERCOME THE SEVERE CERVICAL DYSTONIA

20

THAT SHE HAS HERE.

HERE'S A PATIENT WITH A CERVICAL DYSTONIA THAT SHE'S YOUNG, SHE IS BRIGHT, SHE'S

WE DON'T HAVE TIME TO PLAY ALL THE MOVIES,

21 22

BUT I'D LIKE TO SHOW YOU WHAT HAPPENED WITH HER AFTER

23

SHE HAD THE DEEP BRAIN STIMULATORS AND WENT THROUGH

24

SENSORIMOTOR RETRAINING.

25

NEXT ONE.

LET'S GO ON.

GO TO THE TOP LEFT.

31

GO ON TO THE

1

SO HERE'S THE SAME PATIENT APPROXIMATELY

2

EIGHT WEEKS -- YOU WANT TO PRESS THE MUTE BUTTON.

3

HERE SHE IS ABOUT EIGHT WEEKS AFTER THE DORSAL

4

STIMULATORS HAVE BEEN PLACED IN THE GLOBUS PALLIDUS.

5

WE'VE NOW BEEN WORKING ON THE SENSORIMOTOR TRAINING,

6

AND YOU CAN SEE THAT SHE IS ABLE TO BETTER CONTROL HER

7

HEAD POSITION EVEN WHEN SHE'S WALKING, WHICH YOU SAW

8

BEFORE WAS THE WORST THAT SHE DID WAS WALKING, AND THEN

9

CREATING THE CERVICAL TORTICOLLIS.

10

SO

IF WE GO TO THE NEXT PICTURE ON THE RIGHT,

11

YOU CAN SEE THAT SHE'S -- STOP THE ONE ON THE LEFT, AND

12

THEN GO TO THE ONE ON THE RIGHT.

13

EIGHT WEEKS SHE'S STILL HAVING TROUBLE ORIENTING

14

HERSELF TO GRAVITY.

15 16 17

YOU CAN SEE THAT AT

WHY DON'T WE GO TO THE NEXT ONE. ONE DOESN'T WORK.

MAYBE THAT

GO AHEAD.

SO NOTICE THAT WHEN SHE CHANGES THE POSITION

18

OF HER ARMS, IT ALSO TENDS TO HEIGHTEN HER AWARENESS OF

19

WHERE HER HEAD IS IN SPACE, HELPS HER ORIENT HER HEAD,

20

AND THE IDEA OF FINDING THE KINDS OF THINGS THAT SHE

21

NEEDS TO DO AT HOME TO CONTINUE TO MOVE HER FORWARD IN

22

ORIENTING TO GRAVITY AND OTHER SENSORIMOTOR

23

ADJUSTMENTS.

24

RIGHT THAT I HAVE HER DOING EVERYTHING SHE CAN THINK OF

25

TO DO THAT BRINGS HER HEAD INTO NEUTRAL.

AND YOU WILL SEE IN THIS PICTURE ON THE

32

SO HERE SHE

1

IS JUST TRYING TO MOVE HER HEAD BACK AND FORTH WITH

2

GRAVITY ELIMINATED BECAUSE WHEN GRAVITY IS ELIMINATED,

3

SHE ACTUALLY HAS MORE CONTROL OF HER HEAD.

4

AND IF WE GO TO THE NEXT PICTURE AND STOP

5

THAT ONE, YOU WOULD SEE THAT I GET HER ON HER ALL FOURS

6

AGAIN, AND YOU WILL SEE HER RIGHT HER HEAD, AND YOU CAN

7

SEE IT'S EASIER FOR HER, AGAIN, TO BRING HER HEAD INTO

8

NEUTRAL WHEN SHE'S ON ALL FOURS AS OPPOSED TO WHEN SHE

9

IS UPRIGHT.

AND IN THE PICTURE ON THE RIGHT, YOU WILL

10

SEE THAT SHE CAN GET INTO A SIDE LYING POSITION AND HER

11

HEAD LOOKS GREAT.

12

NEEDS TO DO WHEN SHE IS HOME PLAYING WITH HER SON AND

13

TRYING TO DO WHAT IS THE NORMAL MOVEMENT TO REINFORCE

14

THE BENEFIT OF THESE STIMULATORS AS OPPOSED TO THE

15

ABNORMAL MOVEMENT.

16 17 18

OKAY.

THESE ARE ALL THE THINGS THAT SHE

SO MAYBE WE SHOULD GO AHEAD WITH THE

QUESTIONS. THE MODERATOR:

WE HAVE MORE QUESTIONS.

19

THANK YOU.

20

THERAPISTS ENGAGED IN THIS TYPE OF LEARNING-BASED

21

TRAINING THESE DAYS?

22

SO WHAT IS THE CASE?

DR. BYL:

ARE MOST PHYSICAL

TRADITIONALLY THE REPETITION, THE

23

ATTENTION, THE PROGRESSION OF DIFFICULTY, AND THE KIND

24

OF STAGED PROGRESSION OVER TIME IS VERY HARD TO DO IN

25

THE CURRENT SORT OF THERAPY SETTING.

33

AND I ALSO DON'T

1

THINK THAT PEOPLE ARE READING THE LITERATURE IN

2

NEUROSCIENCE TO KNOW HOW TO APPLY THE BASIC SCIENCE

3

PRINCIPLES TO PRACTICE.

4

THRUST OF NIH IS TO WORK TOWARDS TRANSLATIONAL AND

5

CLINICAL RESEARCH.

6

TRYING TO DO ABOUT LEARNING-BASED TRAINING.

7

AND AS YOU KNOW, THE NEW

AND THIS IS EXACTLY WHAT WE'RE

SO MY GOAL IS THAT WE NEED TO SHARE THIS

8

INFORMATION AS WIDELY AS WE CAN, AND THEN WE NEED TO

9

INTEGRATE WITH ENGINEERS TO REALLY GET THE NEW

10

TECHNOLOGY TO MAKE THIS MORE FUN, TO PROGRESS IT IN

11

SMALLER INSTRUMENTS, AND MAKE IT POSSIBLE FOR PEOPLE TO

12

DO THIS AT HOME.

13

IN AND RECEIVE REIMBURSEMENT AND THERAPY BY COMING IN

14

TO SEE THE THERAPIST FOR ALL THE REPETITIONS THAT ARE

15

NECESSARY TO CHANGE THE BRAIN.

I DON'T BELIEVE THAT PEOPLE CAN COME

THE MODERATOR:

16

AND ACTUALLY WILL INSURANCE

17

PAY FOR THIS TYPE OF TRAINING?

18

PRACTICE?

19

DR. BYL:

IS THAT THE COMMON

WELL, IN CALIFORNIA, AND MANY OF

20

YOU ARE NOT FROM CALIFORNIA, WE CERTAINLY ARE SORT OF

21

STRUGGLING WITH THE SORT OF CAPITATED PACKAGES OF

22

HEALTHCARE.

23

CAREFUL REVIEW OF THE STUDIES AND SHARING THE

24

LITERATURE ON TREATING FOCAL DYSTONIA AND APPLYING

25

BEHAVIORAL NEUROSCIENCE TO PRACTICE, I HAVE BEEN ABLE

AND THROUGH WORKERS COMPENSATION AND

34

1

TO GET APPROVAL FOR PATIENTS TO GET A SERIES OF

2

TRAINING SESSIONS WITH ME.

3

THEM VIDEOTAPES AND HANDBOOKS AND ACTIVITIES THAT THEY

4

CAN COME AND CONTINUE TO DO AT HOME EVERY DAY EVEN

5

THOUGH THEY MAY ONLY SEE ME ONCE A WEEK OR ONCE A

6

MONTH.

7

THERAPIST, THAT THEY NEED TO UNDERSTAND THE PRINCIPLES,

8

THEY NEED TO KNOW HOW TO APPLY THEM, AND THAT, IN FACT,

9

SOME WILL BE REIMBURSED FOR THEIR THERAPY, BUT THE BULK

BUT THE GOAL IS TO GIVE

SO MY GOAL IS TO MAKE EVERY PATIENT THEIR BEST

10

OF THE TRAINING MUST GO ON WITH THE PATIENT AND THEIR

11

OWN SELF-MOTIVATION TO IMPROVE. THE MODERATOR:

12

THANK YOU.

ANOTHER QUESTION.

13

IF A PERSON HAD AN INTERRUPTION OF THEIR INPUT TO THE

14

SENSORY AREAS OF THE CORTEX, THEN PRESUMABLY THERE IS

15

SOME ALTERATION OF THE CORTICAL MASS.

16

TO WANT TO CREATE A SMART PROSTHESIS ACTIVATING THESE

17

AREAS, SAY, FOR SENSORY SUBSTITUTION, THEN THE CORTEX

18

MAP MIGHT NOT BE USEFUL.

19

WITH PLASTICITY THAT LEADS TO REMAPPING, AND INPUT

20

COULD BE PROVIDED THAT MIGHT RELATE TO THE DESIRED

21

SENSORY SUBSTITUTION? DR. BYL:

22

IF ONE WERE NOW

CAN YOU CONCEPTUALIZE HOW

WELL, I'M NOT SURE THAT SENSORY

23

SUBSTITUTION IS WHAT I WOULD CONSIDER POSITIVE

24

LEARNING.

25

YOU ARE GOING TO TRY TO RECRUIT DIFFERENT AREAS OF THE

IN THE CASE OF A PATIENT POST STROKE, THEN

35

1

BRAIN TO BE USED FOR AREAS THAT HAVE BEEN DAMAGED.

2

IN PATIENTS WITH FOCAL HAND DYSTONIA, THEY DON'T HAVE

3

AN AREA THAT IS, QUOTE, DAMAGED.

4

THAT HAS BEEN SORT OF REORGANIZED IN AN ABERRANT WAY,

5

AND THE GOAL IS TO CHANGE THAT MAP SO THAT IT IS

6

PROCESSING INFORMATION IN A NORMAL WAY TO PRODUCE THE

7

NORMAL OUTPUTS.

8

RIGHT APPROACH FOR A PATIENT WITH DYSTONIA.

9

SUBSTITUTION MAY BE THE RIGHT STRATEGY FOR A PATIENT

10 11

BUT

THEY HAVE AN AREA

SO I DON'T THINK SUBSTITUTION IS THE BUT

WITH A STROKE. SO WHAT YOU DO IS YOU TRY TO FIND THE THINGS

12

THEY CAN DO AND THE POSITIONS THAT THEY CAN DO THOSE IN

13

WHERE THEY HAVE THE MAXIMUM.

14

NEURONS THAT ARE AVAILABLE TO THEM, BOTH SENSORY AS

15

WELL AS MOTOR.

16

MORE TIME IN PHYSICAL THERAPY DEALING WITH THE MOTOR,

17

LOOKING AT THE MOTOR OUTPUTS, AND VERY LITTLE TIME

18

LOOKING AT THE SORT OF SENSORY GUIDED MOVEMENTS WHICH

19

ARE ABSOLUTELY ESSENTIAL FOR HAVING NORMAL MOVEMENTS

20

EITHER POST STROKE, POST HEAD INJURY, POST TUMOR, OR IN

21

THE CASE OF DYSTONIA.

22

YOU WANT TO USE THE

AND I THINK UNFORTUNATELY WE SPEND MUCH

THE MODERATOR:

THANK YOU.

ANOTHER QUESTION.

23

YOUR STUDIES SHOW THAT REPEATED HAND USE CAUSE CORTICAL

24

CHANGES, AND SOME OF THESE CHANGES COULD BE ABERRANT.

25

REPETITIVE USE REHABILITATION THERAPY HAS BEEN

36

1

SUGGESTED AS AN APPROACH FOR IMPROVED RECOVERY AFTER

2

NEUROTRAUMA AND STROKE.

3

UTILIZED TO PROVIDE SUCH A THERAPY.

4

APPROACHES DO YOU SUGGEST SHOULD BE CONSIDERED IN USE

5

OF NEUROPROSTHESIS FOR REHABILITATIVE THERAPY?

6

DR. BYL:

NEUROPROSTHESIS COULD BE WHAT CAUTIONARY

I THINK THE SAME AS I MENTIONED

7

FROM THE APPLICATION OF NEUROSCIENCE TO PRACTICE, THAT

8

THE TYPES OF ACTIVITIES THE NEUROPROSTHESIS IS

9

ENCOURAGING MUST BE ATTENDED, THEY MUST BE PRACTICED,

10

THEY MUST HAVE VARIABILITY, THEY MUST BE PROGRESSED IN

11

DIFFICULTY, THEY MUST BE SPACED OVER TIME, AND THEY

12

MUST GIVE REWARD AND FEEDBACK, AND GIVE SOME

13

INFORMATION ABOUT ERROR AND CORRECTION, AND SOME

14

FEEDBACK ABOUT THE QUALITY OF PERFORMANCE.

15

YOU CAN'T ALLOW A PERSON TO MOVE FORWARD AND

16

HAVE A HABITUAL JUST RAPID ALTERNATING RESPONSE

17

CREATING WHAT IS -- WHAT I WOULD CALL NEAR

18

STEREOTYPICAL MOVEMENTS THAT OCCUR SO RAPIDLY IN TIME

19

THAT THEY CAN'T BE INTEGRATED OVER TIME, THIS SORT OF

20

TEMPORAL CONSTANTS IF YOU WILL.

21

PROSTHETIC DEVICES HAVE A MUCH GREATER ABILITY TO DO

22

THAT AND TO MEASURE HOPEFULLY SOME INTERACTIVE FORCE OR

23

SENSORY FEEDBACK FROM THE DEVICE ITSELF TO PROGRESS TO

24

THE NEXT STEP, JUST MINIMAL DETECTABLE DIFFERENCE, IF

25

YOU WILL, TO PROGRESS LEARNING THAT DOESN'T EXCEED YOUR

37

SO I THINK THAT

1 2

ABILITY TO CODE FOR THAT CHANGE. THE MODERATOR:

ANOTHER QUESTION.

ASSUMING

3

THAT SENSORY INFORMATION RELATED TO THE PROSTHETIC HAND

4

FUNCTION CAN BE DELIVERED TO THE BRAIN VIA SOME TYPE OF

5

NEURAL INTERFACE, WHAT SENSORY MODALITIES ARE MOST

6

LIKELY TO BE CRITICAL FOR ALLOWING RUDIMENTARY

7

MANIPULATION OF AN OBJECT WITH A PROSTHETIC HAND

8

WITHOUT VISION?

9

DR. BYL:

WELL, EVEN THOUGH OUR PRIMARY

10

RESEARCH FOCUSED ON THE SOMATOSENSORY CORTEX, AREA 3 B,

11

WE'RE NOW VERY CLEAR THAT THERE ARE PROBABLY JUST AS

12

MANY OPPORTUNITIES TO ENCODE INFORMATION FROM AREAS 3

13

A, FROM THE MOTOR CORTEX, AND THE SENSORY NEURONS THAT

14

ARE IN THE MOTOR CORTEX, AND I THINK IT'S CRITICAL THAT

15

YOU FOCUS ON THE CUTANEOUS, YOU FOCUS ON THE MUSCLE

16

AFFERENTS, YOU FOCUS ON THE JOINT RECEPTORS, AND YOU

17

FOCUS ON VIBRATION AS A SORT OF A MULTI SORT OF

18

STIMULUS MODALITY.

19

AUDITORY TRAINING IN ADDITION TO WHAT I WAS GOING TO

20

SHOW YOU WITH THAT PATIENT, THE AMOUNT OF SPEECH

21

TRAINING THAT WE WERE ABLE TO DO WITH HER USING THE

22

SAME KIND OF APPROACH.

23

AND I ALSO ENCODE AND WORK ON

SO I THINK ALL THE SENSORY INPUT SYSTEMS ARE

24

IMPORTANT IN GENERALIZING LEARNING, AND WE HAVE

25

CERTAINLY SHOWN THAT WE CAN TRAIN THE SOMATOSENSORY

38

1

CORTEX AND SEE IMPROVEMENTS IN AUDITORY DISCRIMINATION

2

AND ALSO VICE VERSA.

3

ALL SENSORY MODALITIES TO MAKE THE MAXIMUM OPPORTUNITY

4

FOR LEARNING.

SO IT'S IMPORTANT TO INCORPORATE

THE MODERATOR:

5

THANK YOU.

WHERE DO THESE

6

RULES FOR SENSORIMOTOR RETRAINING COME FROM, EMPIRICAL

7

DATA, THEORY, OR COMMON SENSE? DR. BYL:

8 9

WELL, I THINK COMMON SENSE

CERTAINLY HEIGHTENS THE VALIDATION THAT THIS APPROACH

10

IS CORRECT.

HOWEVER, ALL OF THE WORK THAT'S BEEN DONE

11

IN THE KECK CENTER AT UCSF AND PARTICULARLY BY MIKE

12

MERZENICH AND ALL THE FOLKS WHO HAVE STUDIED IN THAT

13

LABORATORY, THAT EVERYONE KNOWS THAT YOU MUST INDEED

14

HAVE SOME WAY TO GET AN ANIMAL TO ATTEND TO THE TASK IN

15

ORDER TO SEE REALLY CHANGES IN LEARNING-BASED

16

STRUCTURE.

17

THEN IT BECOMES HABITUATED, AND YOU NO LONGER RESPOND

18

TO THE STIMULUS.

SO IF YOU'RE NOT GOING TO PAY ATTENTION,

SO IT IS WELL-FOUNDED IN THE BASIC SCIENCE

19 20

RESEARCH.

21

EDUCATION THEORY, PARTICULARLY IN SPECIAL EDUCATION,

22

BUT THE STRONGEST SUPPORT FOR THESE PRINCIPLES REALLY

23

IS ABSTRACTED FROM THE BASIC SCIENCE WORK IN

24

NEUROSCIENCE.

25

I THINK IT'S ALSO BEEN REINFORCED IN

THE MODERATOR:

THANK YOU.

39

ASSUME FOR A

1

MOMENT THAT IT IS IMPOSSIBLE TO USE THE STRATEGIES THAT

2

YOU HAVE DESCRIBED IN YOUR PRESENTATION.

3

CONCEPTUALIZE HOW MIGHT YOU USE A PROSTHETIC DEVICE

4

SUCH AS ONE THAT ENABLES CHRONIC SUBSTITUTIONAL INPUTS

5

TO RESTORE SOME USEFUL FUNCTION IN COGNITIVE DISORDERS?

6

DR. BYL:

CAN YOU

WELL, THAT'S AN INTERESTING

7

COMMENT.

I DID TALK ABOUT SUBLIMINAL KIND OF STIMULI

8

BEING DELIVERED PRIOR TO EXPECTING SOME KIND OF OUTPUT,

9

AND CERTAINLY THERE IS MORE AND MORE EVIDENCE THAT IF

10

YOU HAD A NEUROPROSTHETIC DEVICE THAT WAS PROVIDING

11

STIMULATION, EVEN TO SOMEONE WHO COULD NOT MOVE

12

ANYTHING OR WAS IN COMA POST HEAD INJURY, THAT IT'S

13

QUITE POSSIBLE THAT SOME OF THE INFORMATION THAT'S

14

BEING PROVIDED BY THE NEUROPROSTHESIS IS ACTUALLY BEING

15

PROCESSED BY THE NERVOUS SYSTEM, BUT NOT IN A PLACE

16

WHERE THE OUTPUT COULD BE MEASURED.

17

MENTAL IMAGERY STUDIES THAT HAVE BEEN DONE JUST LOOKING

18

AT ANESTHESIA AND TRYING TO REDUCE THE AMOUNT OF DRUGS

19

NECESSARY TO PUT PEOPLE IN AN ANESTHETIC STATE FOR

20

SURGERY SHOW THAT IF PEOPLE PRACTICE MENTAL IMAGERY

21

PRIOR TO THE SURGERY AND THEY DO SOME IMAGINING AND

22

THEY EVEN BRING MUSIC THAT THEY'D LIKE TO HEAR WHILE IN

23

THE OPERATING ROOM OR STORIES THAT THEY WOULD LIKE TO

24

HEAR, THAT THESE PATIENTS ARE MUCH MORE LIKELY TO TAKE

25

LESS MEDICINES AND TO RECOVER SOONER TO BEGIN TO

40

AND SOME OF THE

1

RESTORE THEIR RECOVERY FROM THE SURGERY ITSELF.

2

SO I THINK NEUROPROSTHETIC DEVICES HAVE JUST

3

A WONDERFUL OPPORTUNITY TO DELIVER BOTH THE AUDITORY AS

4

WELL AS SENSORY STIMULI EVEN THOUGH SOMEONE MAY NOT BE

5

ABLE TO ACTIVELY RESPOND TO IT.

6

SURPRISE, YOU KNOW, THINGS THAT YOU DON'T EXPECT,

7

ELEMENTS OF FUN, NEED TO BE INCORPORATED IN SOME WAY

8

PRIOR TO THE PERSON REALLY BEING ABLE TO ENGAGE FULLY

9

IN THAT LEARNING ACTIVITY. THE MODERATOR:

10

BUT ELEMENTS OF

THANK YOU.

ANOTHER QUESTION.

11

REGARDING THE MIRROR OR ABNORMAL POSITIONS, YOU HAVE

12

THE PATIENT MOVE BOTH HANDS WHILE WATCHING THE

13

REFLECTION OF THE GOOD HAND TO REINFORCE PROPER

14

POSITIONS.

15

PATIENTS.

16

FROM REPETITIVE BUT PHYSIOLOGICAL MOVEMENTS?

17

YOU HAVE MENTIONED SOME SUCCESS FOR SUCH IS THE MIRROR USEFUL FOR PATIENTS WITH PAIN

DR. BYL:

ABSOLUTELY.

DR. MOSELEY IS SOMEONE

18

WHO'S DONE A LOT OF WORK WITH THE USE OF MIRRORS SINCE

19

WE BEGAN TO DESCRIBE THE USE OF THE MIRROR IMAGES.

20

HIS PRIMARY CONCENTRATIONS ARE ON PATIENTS WITH PAIN.

21

AND HE HAS SHOWN THAT IF YOU FOLLOW THAT SERIES OF

22

HANDS, LATERALITY AND POSITIONING AND THE USE OF

23

MIRRORS, THAT HE CAN WITH A TRIAL OF APPROXIMATELY SIX

24

WEEKS REDUCE THE PAIN IN PATIENTS WHO HAVE COMPLEX

25

REGIONAL PAIN BY ABOUT 50 PERCENT.

41

AND

1

IF THE PATIENT REALLY DOESN'T HAVE THE

2

MOVEMENT ON THE AFFECTED SIDE AND THE IDEA OF IMAGINING

3

THE MOVEMENT IS ALMOST IMPOSSIBLE, THEN SOMEONE EITHER

4

AT HOME OR IN THE CLINIC CAN GET ON THE OTHER SIDE OF

5

THE TABLE AND THEN HELP WITH BOTH HANDS.

6

IMAGE REPRESENTS THE ASSISTANCE THAT'S BEING PROVIDED

7

IN THE UNAFFECTED ARM AND THE UNAFFECTED HAND AS WELL

8

AS THE AFFECTED HAND.

9

MIRROR IMAGE YOU MUST DO ON BOTH HANDS BECAUSE IT'S A

SO THE MIRROR

SO WHATEVER YOU DO IN THAT

10

COMPELLING IMAGE, AND IT CAN BE VERY EFFECTIVE BOTH FOR

11

MOTOR CONTROL AS WELL AS FOR PAIN MANAGEMENT.

12

THE MODERATOR:

THANK YOU.

ANOTHER QUESTION.

13

IN THE CONTEXT OF TRAUMATIC INJURIES SUCH (INAUDIBLE)

14

AMPUTATION, IS IT POSSIBLE (INAUDIBLE) THE MOVEMENT

15

PROBLEMS AND PAIN DUE TO LOCAL PATHOLOGIES AROUND THE

16

TRAUMA SUCH AS SPASTICITY FROM THE POTENTIAL OCCURRENCE

17

OF FOCAL DYSTONIAS AND ABERRANT REMAPPING PROBLEMS

18

AROUND THE INJURED AREAS TO CHOOSE APPROPRIATE THERAPY

19

AND STRATEGY?

20

DR. BYL:

THAT IS A VERY COMPLEX QUESTION.

21

DR. RAMACHANDRAN AT UC SAN DIEGO WAS ONE OF THE FIRST

22

PEOPLE TO INTRODUCE THE USE OF MIRRORS AND MIRROR

23

IMAGING TO RESTORE WHAT IS ESSENTIALLY THE PHANTOM LIMB

24

PAIN THAT OCCURS POST AMPUTATION.

25

SEVERAL ARTICLES SUGGESTING THAT ONCE THE PATIENT CAN,

42

AND HE HAS PUBLISHED

1

IN FACT, RESTORE THAT IMAGE OF THAT LIMB BACK TO ITS

2

NORMAL HEALTHY STATE, THEN THEY CAN, IN FACT, GET RID

3

OF PHANTOM LIMB PAIN THROUGH THIS PROCESS.

4

I HAVE FOUND THIS STRATEGY OF USING THE

5

MIRRORS EQUALLY AS EFFECTIVE WORKING WITH A PATIENT

6

POST STROKE OR HEAD INJURY AS I HAVE WORKING WITH A

7

PATIENT WITH DYSTONIA.

8

IT MAY BE LIMITED TO PATIENTS WHO DON'T HAVE SUFFICIENT

9

COGNITIVE ABILITY TO REALLY UNDERSTAND AND TO VISUALIZE

SO I DON'T THINK IT'S LIMITED.

10

THAT IMAGE AS REALLY BEING THEIR AFFECTED HAND OR IN

11

PATIENTS WHO HAVE BILATERAL PROBLEMS AND THEY DON'T

12

HAVE A NORMAL MOVEMENT PATTERN TO FOLLOW ON EITHER

13

LIMB.

14

MIRROR AND THEN WORK WITH THEM ONE LIMB AT A TIME,

15

PUTTING THEIR AFFECTED LIMB BEHIND THE MIRROR.

16

IS POSSIBLE TO PARTNER THEM WITH OTHER PATIENTS AND

17

PARTNER THEM WITH FAMILY MEMBERS OR PARTNER THEM WITH

18

THERAPISTS TO, AGAIN, TAKE ADVANTAGE OF THE POSITIVE

19

FEEDBACK THAT YOU GET FROM HAVING THAT IMAGE LOOK MUCH

20

HEALTHIER THAN IT IS WHEN YOU LOOK AT THE MOVEMENT

21

YOURSELF.

22

IN THOSE CASES I USE MY LIMB AS THE IMAGE IN THE

THE MODERATOR:

THANK YOU.

SO IT

ONE LAST

23

QUESTION, DR. BYL.

WHAT AREAS IN THE BRAIN SHOULD BE

24

TARGETED BY NEURAL INTERFACES TO DELIVER INFORMATION

25

THAT RESTORES SENSORY PERCEPTION OF HAND AND ARM

43

1 2

FUNCTION? DR. BYL:

WELL, THAT'S AN INTERESTING

3

QUESTION, AND I THINK IT'S STILL A DEBATE.

THERE ARE

4

MANY NEUROSCIENTISTS WHO FEEL THAT IF YOU DRIVE CHANGE

5

HARD ENOUGH IN THE CORTEX, THAT IT WILL DRIVE CHANGES

6

IN THE THALAMUS AND THE BASAL GANGLION AND THE

7

CEREBELLUM.

8

THE DEGRADATION OF THE CHANGES IN THE THALAMUS AS WELL

9

AS IN THE SENSORY AND MOTOR CORTEX.

IN OUR ANIMAL MODEL OF TRAINING, WE FOUND

SO THE QUESTION, I

10

GUESS, THAT NEEDS TO BE RESOLVED IS WHAT DO YOU HAVE

11

THE GREATEST ACCESS TO, AND IT MAY WELL BE THE CORTEX

12

BECAUSE IT'S MORE SUPERFICIAL AND THE BRAIN STEM IS

13

MUCH DEEPER, AND IT'S VERY HARD TO GET TO THE THALAMUS

14

DIRECTLY WITHOUT SOME INTRUSIVE DEVICES.

15

BUT I THINK THAT THE NEUROPROSTHETICS MIGHT

16

HAVE TO CONSIDER MORE THAN JUST BRAIN STIMULATION,

17

WHICH WE'RE NOW DOING ON THE CORTEX AND WE ARE DOING IN

18

THE GLOBUS PALLIDUS, BUT IT'S NOT CLEAR.

19

LEARNING IS PROBABLY CEREBELLAR.

20

ADJUSTMENTS TO THE SENSORY AND MOTOR OUTPUTS IS REALLY

21

BASAL GANGLIA, AND THEN THE THALAMUS IS OBVIOUSLY A

22

STATION THAT TRANSMITS THAT INFORMATION TO THE CORTEX,

23

AND PARTICULARLY THE PREFRONTAL CORTEX IS INVOLVED IN

24

PLANNING AND INITIATION AND EXECUTIVE MOVEMENTS.

25

EARLY

LATE LEARNING AND

SO IT'S A COMPLEX QUESTION, AND I THINK WITH

44

1

AN INTERDISCIPLINARY TEAM OF INVESTIGATORS, WE MIGHT BE

2

ABLE TO PROVIDE A BETTER ANSWER FOR WHERE IS THE TARGET

3

GOING TO BE BEST AND MOST EFFECTIVE.

4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

45

THANK YOU.