AplicaAplicaçções da Neurofisiologia no ões da Neurofisiologia no estudo do controlo motor das estudo do controlo motor das

doendoençças do movimentoas do movimento

João Costa

Laboratório EMG e PE. IMM. Faculdade Medicina Lisboa

Unitat de EMG y controlo motor. Hospital Clínic. Barcelona.

SumSumááriorio

• Os “instrumentos” neurofisiológicos

• As técnicas neurofisiológicas

• As doenças do movimento

• Os resultados das técnicas aplicadas às

doenças do movimento e ao controlo motor

• Discussão

““Os instrumentosOs instrumentos””

• EMG

– de Superfície:

• Registo da actividade motora (“muscular”)

– Espontânea (ex: tremor, mioclonias, …)

– Não espontânea

» Estímulos (ex: visual, acústico, eléctrico, …)

» Experiências de Tempo de Reacção

» Reacção de Sobresalto

– Reflexa

• Acelerometria

• TMS

• Outros (Importância da biomecânica e da biofísica!)

Tri - Axial

Graphics tablets for measuring 2D planar movements which have

position sample rates of 100-225 Hz, and detection area sizes of

30 x 30 cm (12" x 12") and 45 x 30 cm (18" x 12").

Graphics tablets report the X-Y position of the pen or puck with a

resolution of 0.02 mm, at a sampling rate of up to 225 Hz, and

distances of up to 2 cm from the tablet. Contact switches on the

tip of the pens allow measuring of transit and touch-dwell times in

sequential movement such as "Fitts Tapping" experiments.

Graphics tablets

Pen computers

Simple reaction time experiment (Givler, 1920).

Group testing of complex reaction times (U.S. Air Force).

Simple Reaction TimeExperimenter and its

modulation by the startlestimulus

ImperativeSignal

IS

SRT

STR

STR + Startle

MAIN NEUROPHYSIOLOGICAL TECHNIQUES FOR THE STUDY OF MAIN NEUROPHYSIOLOGICAL TECHNIQUES FOR THE STUDY OF

MOVEMENT DISORDERS MOVEMENT DISORDERS

•• BehavioralBehavioral physiologyphysiology– EMG and study of movements– Reaction time– Startle– Conditioning– Motor learning

•• EyeEye andand eyelideyelid movementsmovements– Blink rate– Saccades

•• Brainstem Brainstem reflexesreflexes– Trigemino-facial reflexes

• Blink reflex• Perioral reflex

– Trigemino-trigeminal reflexes• Jaw-Jerk• Masseteric inhibitory reflex

– Other brainstem reflexes• Sternocleidomastoid inhibition• Facial responses to other stimuli

•• LongLong latencylatency andand spinalspinal reflexesreflexes

– Cutaneo-muscular and stretchreflexes

– Propriospinal inhibitory circuits

•• EvokedEvoked potentialspotentials

– Somatosensory, visual, auditory

– Event related potentials

•• Transcranial Transcranial magneticmagnetic stimulationstimulation

– Central conduction time

– Threshold

– Cortical excitability

•• NeedleNeedle electromyographyelectromyography

– Anal and vesical sphincter EMG

•• AutonomicAutonomic nervousnervous systemsystem

– Sympathetic skin response

– Heart beat frequency modulation

– Urodynamic/rectal pressure studies

Principais doenPrincipais doençças do movimentoas do movimento

•• SyndromesSyndromes presentingpresenting withwith hyperkinesiahyperkinesia

– Tremor

– Dystonia

– Corea

– Tics

– Myoclonus

•• SyndromesSyndromes presentingpresenting withwith hypokinesiahypokinesia

– Parkinson’s disease

– Progressive supranuclear palsy

– Multisystem atrophy

– Cortico-basal degeneration

NRL Diagnosis

syndrome

Clinicalassessment

Psychology

Radiology

Neurophysiology

Blood tests

Genetics

Pathology

ethiology

topography

pathophysiology

Some symptoms are common to diseases involving central andperipheral nervous systems

During electromyographic examination, we may be able to discoversigns that were missed by the requesting physician

more time devoted to electrophysiological examsclose clinico-electrophysiological correlation

Characterize better the pathophysiological aspects of diseasespresenting with movement disorders

Neurophysiological endophenotyipificationCorrect clinical diagnosisGood communication between clinicians and neurophysiologistsGood technical skill and neurophysiological knowledge

1

2

WHY IS IT INTERESTING TO WHY IS IT INTERESTING TO KNOWKNOW ABOUT ABOUT NEUROPHYSIOLOGICAL STUDIES NEUROPHYSIOLOGICAL STUDIES

IN PATIENTS WITH MOVEMENT DISORDERS?IN PATIENTS WITH MOVEMENT DISORDERS?

Disk electrodes attached over the muscle belly

Recording agonist-antagonist muscles

Recording many muscles along rostro-caudal axis

Avoid recording low frequency artifacts (cables)

Rest, posture, action

Accelerometer recording

Cutaneous electrical stimuli. Recording reflex

responses

Recording evoked potentials to somatosensory stimuli

EMG EMG andand accelerometeraccelerometerassessmentassessment

ofof movementmovement disordersdisorders

TremorTremorMyoclonusMyoclonus

ParkinsonParkinson’’s diseases disease

•Agate et al, 1956.

•Acelerómetros piezoresistivos uni-axiais ou tri-axiais.

(sensibilidade máxima 0.001 mV/cm/s2)

•Determinam o pico de frequênciadominante e a amplitude

TremorTremor

Movimento muscular involuntMovimento muscular involuntáário, rrio, ríítmico, tmico,

originando movimentos oscilatoriginando movimentos oscilatóórios de uma ou rios de uma ou

mais partes do corpo.mais partes do corpo.

Tremor essencialTremor essencial

Grau de Ritmicidade

• Área/integral pico / Área/integral do total (20Hz)

Grau de Ritmicidade

• Área/integral pico / Área/integral do total (20Hz)

• 0.05288 (1º) / 0.11040 = 0.5

• 0.00392 (2º) / 0.11040 = 0.03

Neurophysiological investigations in patients with head tremor.Valls-Sole J, Tolosa ES, Nobbe F, Dieguez E, Munoz E, Sanz P, Valldeoriola F.

Mov Disord 1997 Jul;12(4):576-84

Tremor cefTremor cefáálicolico

10º

1 s

CONTROL SUBJECTCONTROL SUBJECT

Visual Visual signalsignal

Tremor Tremor parkinsparkinsóóniconico, essencial e , essencial e psicogpsicogééniconico

10º

1 s

CONTROL SUBJECTCONTROL SUBJECT

PSYCHOGENIC TREMORPSYCHOGENIC TREMOR

Visual Visual signalsignal

10º

1 s

ParkinsonParkinson

Tremor Tremor essencialessencial

Visual Visual signalsignal

AplicaAplicaçções dos testes neurofisiolões dos testes neurofisiolóógicos no gicos no diagndiagnóóstico diferencial do tremorstico diferencial do tremor

Fisiológico exacerbado vs essencialVariação da frequência com peso no fisiológico exageradoReflexo de estiramento aumentado no fisiológico exagerado

Parkinsónico vs essencialPredomínio de tremor em repouso ou posturaPadrão EMG sincrónico ou alternante entre antagonistas

Tremor vs miocloniasRitmicidadeSalvas e silêncios sincrónicos nas mioclonias

Psicogénio vs orgânicoInconsistênciaExecução de movimentos balísticos

MiocloniasMiocloniasMovimentos involuntMovimentos involuntáários que se repetem, srios que se repetem, súúbitos e breves, que podem bitos e breves, que podem

envolver desde um menvolver desde um múúsculo a segmentos ou mesmo todo o corposculo a segmentos ou mesmo todo o corpo

MiocloniasMioclonias de acde acççãoãoPostural and action myoclonus in patients with parkinsonian type multiple system atrophy

Salazar G, Valls-Solé J, Martí MJ, Chang H, Tolosa ES. Mov Disord, 2000; 15: 77-83.

DistoniaDistonia

ContracContracçções musculares involuntões musculares involuntáárias, rias,

intermitentes e mantidas que originam intermitentes e mantidas que originam

movimentos repetitivos ou posturas anormaismovimentos repetitivos ou posturas anormais

Principais tipos de distoniaPrincipais tipos de distonia

• Generalizadas

• Segmentares

• Focais

– Distonia cervical

– Blefaroespasmo

– Distonias de tarefa

– …

MOV

FLEX

EXT

MOV

FLEX

EXT

CorrelaCorrelaçção ão electrofisiolelectrofisiolóógicagica da distoniada distonia

Deuschl G, Heinen F, Kleedorfer B, Wagner M, Lucking CH, Poewe W.Clinical and polymyographic investigation of spasmodic torticollis.

J Neurol 1992;239:9-15

Distonia CervicalDistonia Cervical

Pattern of movement during chewing

SindromeSindrome MeigeMeige e Distonia Cranianae Distonia Craniana

Blepharospasm

Hemifacial spasm

Control

Spontaneous blinking

Blink ReflexBlink Reflex

R OOc

L OOc

R1 R2

R2c

Blink reflex excitability recovery

Cranial dystonia

Control

Control

Test

pulse

pulse

prepulse

Prepulse Prepulse phenomenonphenomenon

A weak, innocuous stimulus, which isnot able to induce a visible reflexresponse causes effects on the response induced by a subsequent suprathresholdstimulus

SensorySensory modulationmodulation ofof thetheblinkblink reflexreflex in in patientspatientswithwith blepharospasmblepharospasm

Gómez-Wong et al. Arch Neurol., 1998; 55: 1233-1237.

100 ms

0.5 mV Um só registo

original

rectificado

0.2 mV

original

rectificado

Média 20 registos

Média do EMG rectificado

Sem contracção

Contracção ligeira

Contracção máxima

100 ms

0.2 mV

Média de 100-200 registos de EMG rectificado

Normalvolunteer

Dystonicpatient

Normal volunteer

Dystonic patient

Abnormal sensorygating in dystoniaMurase et al., 2000

Distonias de tarefa e Distonias de tarefa e caimbracaimbra de escrivãode escrivão

2 s

Esta es una muestra de mi escritura

Pressão exercida pelos dedos sobre a caneta

Correlação com a actividade electromiográfica do 1ºinterósseo

CONTROL

PATIENT

TMS inTMS inDistoniaDistonia

A) A) decreaseddecreased

corticocortico--cortical cortical

inhibitioninhibitionRidding et al.,

J N N P 1995; 59:493-498

GABA-A

B) B) decreaseddecreased

durationduration ofof thethe

silentsilent periodperiodRona et al.,

Mov Disord; 1998; 13: 118-124

TMS inTMS inDistoniaDistonia

DoenDoençça de Parkinsona de Parkinson

DoenDoençça caracterizada por a caracterizada por bradicinbradicinéésiasia, rigidez, , rigidez,

tremor e alteratremor e alteraçções dos reflexos posturaisões dos reflexos posturais

SIMPLE REACTION TIME TASKSIMPLE REACTION TIME TASK TRIPHASIC PATTERN TRIPHASIC PATTERN ofof a a BalisticBalistic movementmovementHallettHallett et al., 1975et al., 1975

WE

WE

MOV

MOV

0.2 s0.5 mV

‘go’signal

OFF

ON

0

100

200

300

400

500

600

700

800

EMG MOV TASK

off DBS

on DBS

Control

Kumru et al., Mov Dis, 2004. Effects of subthalamic nucleus stimulation on characteristics of EMG activity underlying reaction time in Parkinson's disease. Mov Disord, 2004; 19: 94-100.

SIMPLE REACTION TIME TASKSIMPLE REACTION TIME TASK

Kimura J. Disorders of interneurons

in Parkinsonism. The orbicularis

oculi reflex to paired stimuli.

Brain 1973; 96: 87-96.

Motor Motor ControlControl

Startle and Reaction Time Experiences

Arm movement

Wrist extensors

Deltoid

Sternocleidomastoid

Orbicularis oculi

S

The startle reaction to an auditory stimulus

StepsSteps ofof a a reactionreactiontime time tasktask experimentexperiment

The structure of the basic motor program is going to be significantly modified if the

descending ‘voluntary’ volley collides with that of the startle ‘involuntary’ volley.

This will not occur if the tract carrying the ‘involuntary’ volley is an essential part of

the execution of ‘voluntary’ actions.

Presenting a startling stimulus during preparation for execution of a voluntary ballistic

movement would induce the activation of the reticulospinal tract and a startle reaction

Activation of the corticospinal tract by commands related to the execution of the

voluntary ballistic movement will come on top of the activation induced by the

reticulospinal tract

Voluntary movements are executed through activation of descending cortical and

subcortical motor pathways

However, activation of subcortical motor tracts is considered accessory,

participating just in preparatory or accompanying postural adjustments

Is the response different whenthe ‘go’ signal is interferedwith a startlingstimulus?

STC – Task Specific Channel

SES – Stimulus Evaluation System

TR – Time of Recognition

TI – Time of Initiation

TD – Time of Development

RC – Response Channel

ReactionReaction time time shorteningshortening withwith TMSTMS

OOc

SCM

WExt

WFlex

OOc

SCM

WExt

WFlex

Acc

Acc

ReactionReaction time time shorteningshortening withwith a a startlestartle

‘go’+startle

‘go’

Effect of a loud auditory stimulus on the

voluntary reaction (the StartReact effect)

Valls-Solé. Patterned ballistic movements triggered by a

startle in healthy humans. J Physiol, 1999

Forewarning

‘go’

Level ofreadiness

Task

PREPARATION OF SUBCORTICAL MOTOR PATHWAYS

Forewarning

‘go’

Level ofreadiness

Forewarning

‘go’ +startle

Ben Johnson129 ms

Carl Lewis196 ms

A startle accelerates theexecution of a voluntaryaction.

At the time of the IS, thestartle is larger than in a condition of no preparation

The startle does not modifythe characteristics of thevoluntary motor command

It is possible to have a reaction time shorter thanthe established limits of a voluntary reaction

There is a preparatoryphase preceding the IS

OBSERVATIONSOBSERVATIONS CONSEQUENCESCONSEQUENCES

Motor preparation involvesenhancement of the excitabilityof the system activated in thestartle reaction

The reaction of the goal keeper to the penalty shot

RECORDING Arm: leverEye: vertical and

horizontal

ANALYSISReaction time Number of errorsLearning rate

Trying to intercept a moving targetThe goal-keeper and the penalty shot. Low target velocity

target

arm mov

verticaleye mov

horizontaleye mov

target

arm mov

verticaleye mov

horizontaleye mov

target

arm mov

verticaleye mov

horizontaleye mov

Trying to intercept a moving targetThe goal-keeper and the penalty shot. Very high target velocity

stimulusdelivery

movementrecording

evokedpotential

subjectiveawareness

0

45

3530

25

20

15

10

5

40

50

55Método de Libet para determinação da percepção temporal sensorialLibet et al., Brain 1979;102:193-224.

0

45

3530

25

20

15

10

5

40

50

55Awareness of the motoraction (Libet’s method) is not significantlyadvanced in trials withthe StartReact effect

Conscious awareness of the time of the reaction (a cortical process)is independent from

the execution of the motor task in StartReact trials

REFLEX AND VOLUNTARY REFLEX AND VOLUNTARY COMPONENTS OF THE COMPONENTS OF THE

REACTION TO PULLREACTION TO PULL--TESTTESTI. I. ColmeneroColmenero, J. Costa, J. Costa¹¹, J. Casanova, J. Casanova²², J. Valls, J. Valls--SolSoléé²²

Department of Clinical Neurophysiology, Marques de Valdecilla University Hospital, Santander.

¹Department of Neurology, Santa María University Hospital, Lisbon. ²Department ofNeurology, Clínic i

Provincial University Hospital, Barcelona.

INTRODUCTION & OBJECTIVE

BUT…

What is the pattern of muscular contraction associated with it?

TO DEFINE THIS MUSCLE TO DEFINE THIS MUSCLE ACTIVATION PATTERN IN HEALTHY ACTIVATION PATTERN IN HEALTHY

VOLUNTEERS VOLUNTEERS

PULL-TEST: Manoeuvre widely employed in clinical practice.

OUR AIM

AND THEN…

We could understand the abnormalities that can be seen in patients

METHODS

Sternocleidomastoid

Rectus abdominalis

Quadriceps

Tibialis Anterior

9 subjects Orbicularis Occuli

Soleus

Accelerometer

Synergy electromyograph

Experimenter

Pull backwards

METHODS

Volunteer

Reaction TimeVs

Disequilibrium

Signal of accelerometer

Latency

SCM

QUA

TA

SOL

OOC

ABD

QUA

TA

SOL

OOC

ABD

SCM

Reaction Time

Disequilibrium

100 ms

1 mV

1º

S

S

RESULTS

0.16121±16125±14Soleus

0.0378±17110±18*Tibialis Ant

0.0164±14191±49Quadriceps

0.1658±1264±9Abdominal

0.0272±39125±23SCM

0.1125±528±4OOc

React vs DiseqDisequilibriumReaction

* Bursts of low amplitude in reaction

ABD Reaction Time

Disequilibrium

100 ms

1 mV

OOC Reaction Time

Disequilibrium

SOL

100 ms

1 mV

Reaction Time

Disequilibrium

S

COMMENTS & CONCLUSIONS

1) The first burst of EMG activity in the condition “Disequilibrium” is compatible with a REFLEXREFLEX REACTIONREACTION. .

The latencies are shorter than in the same muscles in the condition “Reaction”.

2) The fact that bursts were observed in most muscles is compatible with a GENERALIZED REACTIONGENERALIZED REACTION.

Possible generatorsSomatosensory afferents Vestibular afferents

RETICULOSPINAL TRACT

COMMENTS & CONCLUSIONS

3) The first muscles to be activated:

•Bisdorff et al. (J Neurol Neurosurg Psychiatry. 1999) : OOC-SCM-ABD

•Our study: OOC- ABD ABD -SCM

The ABD muscles play an important role in maintaining the trunk´scenter of gravity

4) The OOC showed some activity in both manoeuvres.

The tap stimulus in the shoulder is sufficient to induce a SOMATOSENSORY BLINK REFLEXSOMATOSENSORY BLINK REFLEX (Miwa et al., 1998)

COMMENTS & CONCLUSIONS

5) The relationship between TA and SOL is different in both conditions:

The SOL is tonically active during standing AND a burst contraction of SOL while standing is preceded by a PREPRE--MOVEMENT SILENT PERIODMOVEMENT SILENT PERIOD (pmsp) (Aoki et al., 2002).

•In “Disequilibrium”: The SOL pmsp is accompanied by a burst in the TA.•In “Reaction” : The SOL and TA activity are simultaneous.

Present in most trials in our subjects

TA

SOL

1º

2º

1º No feet displacement2º Feet displacement

pmsp

burst

100 ms

1 mV

TA

SOL

S

DISEQUILIBRIUM

FINAL CONCLUSION

The latencies of the motor responses and the pattern of muscular activation recorded during the pull test maneuver is compatible with the activation of the circuit of the startle reaction through either somatosensory or vestibular inputs.

According with this hypothesis, an association can be expected between impairment of the startle reaction and abnormalities in the pull test maneuver.