potentials & perspectives of repetitive sensory stimulation · role of neurotrophic factors in...
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Institut für Neuroinformatik
- Neural Plasticity Lab -Ruhr-Universität Bochum
Hubert Dinse
Potentials & Perspectives
of repetitive sensory stimulation in stroke rehabilitation 0
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rationale for using sensory stimulation
effects in healthy populations
effects in patient populations
future work
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restoration of function
through neuroplasticity mechanisms
training & massed practice
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restoration of function
through neuroplasticity mechanisms
Alternatives:targeted brain activation
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training
how to induce plasticity and learning?
humans
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cells/synapses
training
how to induce plasticity and learning?
repetitive stimulation(spatio-temporal constraints)
humans
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training
how to induce plasticity and learning?
repetitive stimulation(spatio-temporal constraints)
cells/synapses repetitive stimulation(spatio-temporal constraints)
humans
humans
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Nomenclature
“co-activation”“repetitive sensory stimulation”
“passive stimulation”“exposure-based learning”
“peripheral high-frequency stimulation”“peripheral nerve stimulation”
Conforto AB, Kaelin-Lang A, Cohen LG (2002) Ann Neuro 51: 122Celnik P, Hummel F, Harris-Love M, Wolk R, Cohen LG (2007) Arch Phys Med Rehabil 88: 1369Dinse HR, Kalisch T, Ragert P, Pleger B, Schwenkreis P, Tegenthoff M (2005) Transaction Appl Perc 2: 71Gutnisky DA, Hansen BJ, Iliescu BF, Dragoi V (2009) Curr Biol 19: 555Johansson BB, Haker E, von Arbin M, Britton M, Långström G, Terént A, Ursing D, Asplund K (2001) Stroke 32: 707Kalisch T, Tegenthoff M, Dinse HR (2009) Front Neurosci 3: 96Ng SS, Hui-Chan CW (2007) Stroke 38: 2953 Sawaki L, Wu CW, Kaelin-Lang A, Cohen LG (2006) Stroke 37: 246Wu CW, Seo HJ, Cohen LG (2006) Arch Phys Med Rehabil 87: 351Yavuzer G, Oken O, Atay MB, Stam HJ (2007) Arch Phys Med Rehabil 88: 710
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(r=0.724; p=0.018)
3 h coactivationPleger, Foerster, Ragert, Dinse, Schwenkreis, Nikolas,Tegenthoff (2003) Neuron
pre
Relation between reorganization & tactile perceptiontactile co-activation on right index-fingerspatial 2-point discriminationCortical activation: BOLD signals
disc
rimin
atio
nim
prov
emen
t[p
ost -
pre]
normalized SI enlargement [post - pre]
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placebo amphetaminememantine
Dinse, Ragert, Pleger, Schwenkreis, Tegenthoff (2003) Science
med
io-la
tera
l shi
ft[m
m p
re-p
ost]
discrimination improvement [post - pre]
-4
0
4
8
12
0 0.1 0.2 0.3 0.4 0.5
memantine
placebo
amphetamine
pre
post
Relation between reorganization & tactile perceptiontactile co-activation on right index-fingerspatial 2-point discriminationCortical activation: SEP recording and electric source localization
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Höffken, Veit, Knossalla, Lissek, Bliem, Ragert, Dinse, Tegenthoff (2005) J Physiol
decrease in paired pulse suppression (post-pre)
psyc
hoph
ysic
al im
prov
emen
tth
resh
old
post
-pre
(mm
)
r=0.6; p=0.03
pre
3 h coactivation
Relation between reorganization & tactile perceptiontactile co-activation on right index-fingerspatial 2-point discriminationCortical excitability: SEPs after median nerve paired-pulse stimulation
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.
• tactile acuity (2-point discrimination)• frequency (flutter) discrimination• reaction times• Braille sign recognition• fine motor movements (finger–hand)• haptic object recognition• every day life performance
improvement of tactile & sensorimotor performance
Effects of repetitive sensory stimulation
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Spinal cord
Brain stem
Thalamus
repetitive sensory
stimulation
brain activation&
induction of plastic reorganization
Effects of repetitive sensory stimulation
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Spinal cord
Brain stem
Thalamus
repetitive sensory
stimulation
LTP-like processes
Δ synaptic efficacy
Δ sensorimotor processing
Δ sensorimotor behavior
brain activation&
induction of plastic reorganization
Effects of repetitive sensory stimulation
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Co-activation in healthy elderly subjects
Kalisch, Tegenthoff, Dinse (under revision)
Peg board - pin plugging65 to 89 yrs
0
5
10
15
20
25
30
post post 2weeks
post 3weeks
post 4weeks
rec 1week
rec 2weeks
Tim
e –
gain
rela
tive
to p
re[%
]
right hand co-activated 2 days / week for 4 weeks
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Application of repetitive sensory stimulationin the treatment of impaired subpopulations
.
improvement of sensorimotor performancein patients suffering from stroke
targeting: - touch- proprioception- haptics- motor performance
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Application of repetitive sensory stimulationin the treatment of impaired subpopulations
improvement of sensorimotor performancein patients suffering from stroke
advantages: - easy to apply- easy to use at homes- high compliance- inexpensive
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Application of repetitive sensory stimulationin the treatment of impaired subpopulations
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9-holepegboard
Hand tapping
Touch threshold
Haptic object/form recognition
Practical tasks (Wolf-Motor/JTHF)
Tactile acuity
Moberg
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Stimulation statistics: intermittent high-frequency
- electrical stimulation of the fingers
- trains of pulses with an inter-train interval of 5 s
- train duration 1 sec with 20 single pulses @ 20 Hz
- single pulse duration 200 microsec
- pulse trains stored digitally and played back via MP3 player allowing unrestricted mobility of the subjects during stimulation
stimulation session of 1 hour 12000 stimuli
.
Ragert, Kalisch, Bliem, Franzkowiak, Dinse (2008) BMC Neuroscience
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Subacute patientsage 55 to 76 years post-stroke: 4.2 ± 1.3 weeksmedia infarct, thalamic infarct
stimulation: 45 minutes 5 days / week, for 2 weekstotal: 7.5 h, ~90.000 stimulifollow-up after 3 months
complementary treatment:standard physiotherapy
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Grating orientation taskTactile acuity
disc
rimin
atio
n th
resh
old
(mm
)
01
23
45
67
8
Baseline End-treatment
Follow-upmidtreatment
no discrimination ability
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Grating orientation taskTactile acuity
disc
rimin
atio
n th
resh
old
(mm
)
01
23
45
67
8
Baseline End-treatment
Follow-upmidtreatment
-40
-30
-20
-10
0
End-treatment Follow-upmid
treatment
no discrimination ability
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Time to pick up and to correctly identify item
Moberg
0
20
40
60
80
Tim
e (s
ec)
Baseline End-treatment
Follow-up
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Time to pick up and to correctly identify item
Moberg
0
20
40
60
80
Tim
e (s
ec)
Baseline End-treatment
Follow-up
-60
-50
-40
-30
-20
-10
0
End-treatment Follow-up
chan
ge in
per
form
ance
(%
to b
asel
ine)
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0
10
20
30
40
Tactileacuity
Formrecognition
Mobergpick up
9-holepegboard
impr
ovem
ent (
%)
End-treatment
Follow-up
Comparison of restoration effects - subacute
Dinse, Bohland, Kalisch, Kraemer, Freund, Beeser, Hömberg, Stephan (2008) Europ J Neurol
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R2 = 0.2938-40
-30
-20
-10
00 10 20 30 40 50
R2 = 0.4402-80
-60
-40
-20
00 20 40 60 80
at end-treatment
performance at baseline (sec)
perc
ent c
hang
e (%
)
Moberg9-holepegboard
perc
ent c
hang
e (%
)baseline dependence
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R2 = 0.7106-40
-30
-20
-10
00 10 20 30 40 50
R2 = 0,576-80
-60
-40
-20
00 20 40 60 80
at follow-up
performance at baseline (sec)
perc
ent c
hang
e (%
)
perc
ent c
hang
e (%
)baseline dependence
Moberg9-holepegboard
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Chronic patientsage 57 to 67 years post-stroke: 30 ± 1.3 monthsmedia infarct
stimulation: 90 minutes 4 days / week, for 6 weekstotal: 36 h, ~400.000 stimulifollow-up after 4 weeks
complementary treatment:n.a.
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Improvement in chronic stroke patients
Smith, Dinse, Kalisch, Johnson, Walker-Batson (in press) Arch Phys Med Rehabil
left hemispheric stroke
S 1 6 monthsS 2 18 months
0.0
0.2
0.4
0.6
0.8
1.0
baseline mid end follow-up
Rat
io:
affe
cted
/ hea
lthy
side
S 3 60 monthsS 4 36 months
0.0
0.2
0.4
0.6
0.8
1.0
baseline mid end follow-up
Rat
io:
affe
cted
/ hea
lthy
side right hemispheric stroke
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Improvement in chronic stroke patients
tapping
0.0
0.2
0.4
0.6
0.8
1.0
baseline mid end follow-up
Rat
io a
ffec
ted
/ hea
lthy
side
Haptic object
0.0
0.2
0.4
0.6
0.8
1.0
baseline mid end follow-up
Rat
io a
ffec
ted
/ hea
lthy
side
Smith, Dinse, Kalisch, Johnson, Walker-Batson (in press) Arch Phys Med Rehabil
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Chronic patientsage 38 to 61 years post-stroke 4.8 ± 2.5 yearsmedia infarct, thalamic infarct
stimulation: 45 to 60 minutes 5 days / week, for 6 to14 monthstotal: > 1 million stimulifollow-up every 2 to 4 months
complementary treatment:n.a. / general physiotherapy
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• touch threshold (Frey Hairs)
• tactile acuity (GOT, 2PD)
• haptic object recognition
• hand/arm motor performance (MLS)
• multiple choice reaction times (visuo-tactile task)
• Actigraphy
• hand functions in daily activities (Jebsen Taylor, video-based)
• SEPs (high density EEG)
Effect of repetitive sensory stimulation (chronic patient, right-handed, 48 years, left thalamus infarct 1997 )
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digit 2 right
digit 4 right
baseline 7 weeks 22 weeks 36 weeks
0
50
100
150
200
250
300
350
after 36 weeks: ~2 million stimuli
Touch thresholdth
resh
old
(mN
)
no sensation
healthyleft fingers
Effect of repetitive sensory stimulation(chronic patient, right-handed, 48 years, left thalamus infarct 1997 )
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Multiple choice reaction times
baseline
left right
7 weeks 22 weeks 36 weeks
RT
(ms)
1600
1200
800
400
0
Effect of repetitive sensory stimulation(chronic patient, right-handed, 48 years, left thalamus infarct 1997 )
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0
10
20
30
40
50
60
70
80
90
100
baseline 7 weeks 36 weeks
Hand dominance test (HDT)
Effect of repetitive sensory stimulation(chronic patient, right-handed, 48 years, left thalamus infarct 1997 )
HD
T sc
ores
extreme left handedness
extreme right handedness
right handedness
left handednessambidexterity
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SEPs (high density EEG) air-puff stimulation, right digit 2
baseline
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baseline
after 36 weeks
SEPs (high density EEG) air-puff stimulation, right digit 2
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Future work
Optimization & development of RSS protocols
Optimization & development of RSS devices
Role of neurotrophic factors in RSS
Individual strategies for combining RSS with training
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Future work
Optimization & development of RSS protocols
Optimization & development of RSS devices
Role of neurotrophic factors in RSS
Individual strategies for combining RSS with training
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Future work
Optimization & development of RSS protocols
Optimization & development of RSS devices
Role of neurotrophic factors in RSS
Individual strategies for combining RSS with training
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Evolution of stimulation devices…
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Role of neurotrophines in RSS
family of growth factors– produced in blood and brain
NGF – nerve growth factor
BDNF – brain-derived neurotrophic factor
Production & maintenance of connections between nerve cells
Synaptic plasticity
Neurogenesis
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Mattson (2008) Ageing Res Rev
Sensory stimulation
Growth factorsStress resistance genesEnergy metabolismAntioxidant enzymesHeat shock proteins
Mild / transientCellular stress
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Future work
Optimization & development of RSS protocols
Optimization & development of RSS devices
Role of neurotrophic factors in RSS
Individual strategies for combining RSS with training
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Summary & Conclusion
Repetitive sensory stimulation (RSS) was used as stand-alone or complementary rehabilitation therapy in subacute and in chronic stroke patients
RSS consisted of intermittent high-frequency electrical stimulation of the fingers of the affected hand
RSS improved hand-arm functions of the affected side for touch, tactile and haptic performance, proprioception and motor performance
Improvement was preserved or further enhanced several weeks follow-up
Two advantages: RSS is inexpensive and passive, i.e. it does not require the active cooperation of the patient
These properties together with the effectiveness make RSS-based principles prime candidates for therapeutic intervention, particularly for out-patients
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Tobias Kalisch, Jan Kattenstroth
Martin Tegenthoff, Oliver Höffken
Volker Hömberg, Klaus Martin Stephan, Matthias Kraemer
Wolfgang Greulich, Petra Gerhardt
Delaina Walker Batson, Patricia S. SmithMark Johnson
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Thank you for your attention
RuhrUniversityBochum