2011.10.07.. TÁMOP–4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework** Consortium leader PETER PAZMANY CATHOLIC UNIVERSITY Consortium members SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund *** **Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben ***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg. PETER PAZMANY CATHOLIC UNIVERSITY SEMMELWEIS UNIVERSITY sote_logo.jpg dk_fejlec.gif INFOBLOKK 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 2 Peter PazmanyCatholicUniversity Facultyof InformationTechnology ELECTROPHYSIOLOGICALMETHODSFORTHE STUDYOF THE NERVOUS-AND MUSCULAR-SYSTEMS LECTURE7 EVENT-RELATEDPOTENTIALS www.itk.ppke.hu Az ideg-és izom-rendszer elektrofiziológiai vizsgálómódszerei (Eseményhez kötött potenciálok) BALÁZS DOMBOVÁRIand GYÖRGY KARMOS Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 3 AIMS: In this lecture, the student will become familiar with the different categories of the event related potentials, characteristics of ERP components, the recording techniques, and with the relevance of ERP method in the clinical practice. Event-related Potential (ERP): Any potential elicited by and time locked to a sensory stimulus, or associated with an event, execution of a motor, cognitive, or psychophysical task. Evoked potential (EP): Wave or complex elicited by and time-locked to a sensory or other stimulus, for instance an electrical stimulus, delivered to a sensory receptor or nerve, or applied directly to a discrete area of the brain. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 4 GENERAL CHARACTERISTICS OF THE ERPs ERPsare usually composed of several deflections of positive or negative polarity. Deflections having a functional relevance are called components. They are described by their scalp distribution, polarity and peak latency. N100refers to a negative peak with a latency around 100 ms.Earlier ERP components were numbered according to their temporal appearance (e.g. P1, P2, P3). Parameters of the short latency, early components are usually depend on the physical parameters of the evoking stimulus therefore they are called „exogenous components”. Longer latency components are determined more by the relevance of the stimulus in the given situation. The same stimulus depending its significance may or may not elicit a component. They are called „endogenous components”. Some components can be influenced both by the physical parameters of the stimulus and by its relevance, they are named „mesogenous”. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 5 CLASSIFICATION OF ERPS: Type of event:• Sensoryevoked potential • Motor potential • Event-related synchronization /desynchronization • Induced response • Etc. CLASSIFICATION OF THE COMPONENTS OF ERP: By latency:• Early components • Mid latency components • Late components By nature of the evoking effect:• Exogenous components • Mesogenouscomponents • Endogenous components Exogenouscomponentsof thesensoryevokedpotentialsareusedinclinicalpracticetotest thefunctionof thesensorypathways. The endogenouscomponentsmaychangedependingonthesubjectsprior experience, decisionsand intentios; aremodulatedbythetaskparametersandtheinstructions. Theyareusedincognitivepsychophysiologyand clinicalpsychology. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 6 THE CORRECTIVE EFFECT OF AVERAGING ON SIGNAL TO NOISE RATIO EEG epochs containing a given type of event (mostly a stimulus) are extracted from EEG. These are aligned with respect to the event and averaged together. A single epoch consist of an ERP plus the spontaneous EEG, regarded as random noise. The amplitude of the ERPsis usually small (0.1-5 µV) compared to the spontaneous EEG activity (up to several hundred µV). Basically every ERP waveform is assumed to be identical whereas the noise assumed to be completely unrelated to the event. The task is to extract ERP waveforms from epochs. If every ERP waveform look exactly the same on every trial, averaging together several trials will yield the same waveform that was present on the individual trials. In contrast the noisewhiochis random on every trial, so the average of a large number of trials will be a zero. In summary, the average of many trials containing both ERP waveforms and random noise will consist of reduced noise and amplified ERP waveform. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 7 THE CORRECTIVE EFFECT OF AVERAGING ON SIGNAL TO NOISE RATIO (CONT.) Moreprecisely: IfRistheamountofnoiseonatrial,Nisthenumberoftrials,thenthesizeofnoiseinanaverageoftheNtrialswillbe: (1/.N)~R Example: In an experiment if we are measuring acoustic evoked potentials with an amplitude of 10 µV and the actual noise is 40µV on a single trial, then the signal to noise ratio (SNR) will be 10/40=0.25, which is not very good.To increase SNR from 0.25 to 2 it is necessary to average 64 trials, because .64=8. (SNR increases as a function of the square root of the number of trials.) Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 8 AVER Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 9 CHARACTERISTICS OF EVENT RELATED POTENTIALS SHOWN ON THE AUDITORY ERP Earlycomponentse.g. auditorybrainstempotential(BAEP) Middlelatencycomponents Latecomponents(e.g. slowauditoryresponse) Exogenous-Endogenous-(Mezogenous)-components Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials V www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 10 EXAMINATIONOF THEAUDITORYPATHWAYBY ERP Right Ear VentralCochlearNucleus DorsalCochlearNucleus SuperiorOlivaryComplex LateralLemniscus InferiorColliculus MedialGeniculateBody Right Auditory Cortex VentralCochlearNucleus DorsalCochlearNucleus SuperiorOlivaryComplex LateralLemniscus InferiorColliculus MedialGeniculateBody LeftEar LeftAuditory Cortex BrainstemAuditory EvokedPotential(BAEP) BAEP Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials Picture3a www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 11 EFFECT OF STIMULUS INTENSITY ON THE BAEP The traditional audiometry is subjective technique to measure hearing threshold. The BAEPas an exogenous response can be used to determine the hearing threshold(objectiveaudiometry). Usually the amplitude and latency of component V is measured. Its latency is inversely while its amplitudeis nearly linearly related to the stimulus intensity (dB). The advantage of brainstem audiometry is that the hearing threshold can be tested even in unconscious subjects or in newborn babies. Because of its short latency the BAEPcan beelicited by high rate repetitive stimuli. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 12 BRAINSTEMRESPONSESINCOMA Picture5a day4 day7 day8 day9 day10 EEG is widelyusedinthediagnosing of the cerebral death.In coma patients the BAEPmay show the gradual deterioration of the brain stem functions. This way the loss of BAEPcomponents is also confirmatory for brain death. The figure shows the changes of the BAEPcomponents in a serious coma patient. The days indicate the days after an anoxic event. On day 4 the patients displayed withdrawal responses to noxious stimuli and the cephalic reflexes were preserved. These reflexes were no longer present at day 8 and the EEG became flat. From day 10 the responses to noxious stimuli were absent, the patient deceased on day 14. The gradual loss of the BAEPcomponents indicate the worsening of the status of the patient. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 13 MIDDLELATENCYERP COMPONENTS The latency range of the middle latency auditory evoked potentials (MLP) is 12-80 ms.They are multiple negative-positive waves named: N0, P0, Na, Pa, Nb. These components reflects the neuralprocesses appearing when the sensory input enters the sensory cortex. The MLPsare primarily exogenous but there are data indicating that they may be modulated by behavioral factors like awareness and attention. They are recorded with highest amplitude above the frontal area of the scalp. The reason is that the auditory cortex is located in the depth of the Sylvianfissure in the temporal lobe and the generators of the MLPproject towards the frontal area (See L. 9.). Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 14 COGNITIVEPSYCHOPHYSIOLOGY Cognitive psychophysiology concerned with the scientific study of biological substrates underlying cognition. It addresses the questions of how psychological/cognitive functions are produced by the brain. Physiological measures like ERP and brain imaging techniques are used to reveal processes of brain information processing. In the following slides ERP paradigms and components studied by cognitive psychophysiology are discussed. The most often used ERP paradigm in cognitivepsychophysiology is the „oddball paradigm”. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials C:\Documents and Settings\gkarmos\Desktop\TÁMOPfileok\oddball.jpg www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 15 ODDBALL PARADIGM The subject is presented with two types of stimuli. One is a frequently occurring, more common stimulus (called standard or non-target) interleaved by infrequently, rare (‘oddball’) stimuli. The ERPselicited by the standard and deviant stimuli are compared. The oddball paradigm can be passive, if the subject has no task to respond to either of the stimuli. In activeoddball paradigm the subject is asked to indicate the occurrence of the rare (target) stimuli by counting or by pressing a button. Auditory stimuli can be presented monaurally, into one ear or binaurally, to both ear. At dichotic stimulation different stimuli are given to the two ears. Binauralauditoryoddball paradigm R L C:\Documents and Settings\gkarmos\Desktop\TÁMOPfileok\fejhallg.jpg R L Standards: -R: right ear Deviants: -L: leftear Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 16 MISMATCH NEGATIVITY Themismatchnegativity(MMN)isanERPcomponenttoadeviantstimulusinasequenceofstandardstimuliinapassiveoddballparadigm. Itcanoccurinanysensorysystem,butithasmostfrequentlybeenstudiedintheauditorymodality.TheMMNcanbeelicitedregardlessofwhetherthesubjectispayingattentiontothestimuli.Duringauditorysequences,apersoncanbereadingorwatchingasilentsubtitledmovie.TheMMNmaybeelicitedwheneverthestandardanddeviantauditorystimuliarediscriminableonanyoftheirfeatures(pitch,intensity,duration). MMNisanegativecomponentinthedifferencecurve(deviantresponse–standardresponse).Itspeaklatencyvariesbetween100-200ms.Theloweristheprobabilityofthedeviant,thehigheramplitudeMMNappear. MMNreflectstheoperationofanautomatic,„preattentive”changedetectorprocessintheauditorycortexrelatedtoearly(echoic)memory. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 17 ANIMALMODELOF MMN MMNcan be demonstrated in animals where electrodes can be implanted into the auditory cortex. In Fig. A auditory evoked potentials recordedfromtheauditorycortexof a catare shown. The standard stimuli were short 1 kHz tone bursts while the deviant stimuli were 2 kHz tone bursts. The MMNcan be seen in the difference curve. In Fig. B the effects of repetition rate (interstimulusinterval) and the deviant probability of the stimuli on the MMNis depicted. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 18 EFFECTOF DEVIATIONOFSTIMULIONMMN G:\My Documents\Pincze\13.abra.jpg Figure A shows thedifferencecurveof a frequencyMMNrecorded from the surface of the auditory cortex of cat. Short tone bursts of 1 kHz were given as standard stimulus. The frequency of deviant stimuli differed from the standard by 20 to 300%. The amplitude and peak latency changes of MMNis depicted in graphs of figure B. M MMN Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 19 N100COMPONENT N100or N1is a negative-going component of the auditory evoked potential. It peaks in adults between 80 and 120 milliseconds after the onset of a stimulus, and distributed mostly over the fronto-central region of the scalp. The auditory N100is generated by a network of neural populations in the primary and association auditory cortices in the superior temporal gyrusin Heschl'sgyrusand planumtemporale. Some generators are located in the frontal areas. The N100component is a typical „mesogenous” component, because it is elicited by any unpredictable stimulus in the absence of task demands. It can be used for objective audiometry because its amplitude depends on the intensity of the stimulus (may test the function of the auditory cortex). The N100also is endogenous because it is characteristically influenced by selective attention. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 20 EFFECT OF SELECTIVE ATTENTION ON N100COMPONENT Activeoddballparadigm,dichoticlisteningtask(seeS.14.).Standardstimuliareshorttonesgivenrandomlytotherightandleftears(e.g.1000and2000Hz)withshortinterstimulusinterval(~300ms.).Thesubjecthastocountthehigherintensitydeviantstimuligiventotheselectedear. ERPselicitedbystimuligiventoeachearareselectivelyaveraged.Responseswerecomparedwhethertheearwasattendedorunattended.ResponsestostimuligiventotheattendedeartheN100componentappearedwithhigheramplitude. Conclusion:Enhancedresponseattheattendedchannel! Right ear Leftear Attended ear: Unattended ear: Fzlead Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP–4.1.2-08/2/A/KMR-2009-0006 21 P300COMPONENT Endogenous components appearing to deviant stimuli in active oddball paradigm with latency around 300 msare called P300. Amplitude of P300 is sensitive to stimulus probability, meaning of the stimulus, and the psychological resources allocated to itsprocessing of it. The more complex are the stimuli to be processed the latency of the P300 is longer. Mental chronometry: P300 latency may reflect the stimulus evaluation or categorization time. In dual-task paradigms P300 amplitude to the concurrent secondary task decreases depending on the perceptual/cognitive demand of the primary task. The P300 may be related to the closure of the perceptional processing or to the memory update after processing of the deviant stimulus. Recently P300 component is successfully used in brain-computer interface studies. In psychophathologicalcases (e.g. dementia) characteristic P300 changes appear. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 22 MENTAL CHRONOMETRY Stimulus Semantic categorization task: Task 1: distingushtwo names Task 2: distinguish female and male names Task 3: recognize the synonimsof a name Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 23 NOVELTYP300INACOUSTICTASKPARADIGM If in an active acoustic oddball paradigm additional unexpected novel stimuli are rarely interspersed a positive deflection similar to „classical” P300appear. It is called „Novelty P300”. It appears with frontal scalp distribution while the classical P300has a centro-parietal maximum. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 24 SCALP DISTRIBUTION OF ACOUSTIC ERPBRAIN MAPPING Untitled-1 Scalp distribution of the ERPscan be displayed in „EEG brain maps”. The topography of ERP amplitude is color coded. These maps are stylized representations, not anatomically accurate rendering. Brain maps are used to display EEG frequency distribution and compare ERP component distributions in task situations. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 25 DISTRIBUTIONOF ACOUSTICERPDURINGTASK N1, P300 Untitled-3 Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 26 LANGUAGE RELATED ERP COMPONENTS N400 Semantic processing are reflected in cognitive ERP. A typical experiment is the sentence reading task. It usually involves computer presentation of words one-by-one to form a sentence. If a sentence is ending with a semantically incongruous word a negative late component with latency around 400 mscalled N400appears. The amplitude of the N400is proportional with the degree of incongruity. N400componentisspecificallysensitivetoviolationofsemanticexpectancies. Inthesameexperimentmorphosyntacticchangeofthewords(lettersize,capitalletters)inducealatepositivewavecalledP600.See:KutasandHillyard:Science,1980,207:203-205fig.1. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 27 MOVEMENT RELATED POTENTIALS A characteristic ERP is the slow potential change that can be recorded on the scalp above the motor cortex before the self-paced movements. The paradigm is that the subject is instructed to initiate flexion of the index finger repetitively every 10 s. The EMG signal is used as trigger and the EEG activity is averaged backward recording the ERP before the movement. A negative deflection beginning about 800 ms before the movement is called „readiness potential”or „Bereitscahftspotential”(the German Kornhuber and Deecke described first the phenomenon). The readiness potential is related to the preparation of the movement. During the movement execution further components of the movement related ERP appear called „reafferentpotentials” they are evoked by the afferents from the moving muscle. The readiness potential has higher amplitude contralateral to the given movement. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 28 CONTINGENT NEGATIVE VARIATION (CNV) CNV is a slow ERP that can be recorded in the so called fore period of a warned reaction-time task. This means that a warning stimulus (S1) is given before the imperative stimulus (S2) to which the subject has to respond. The warning stimulus elicits firstthe modality specific evoked response.Afterit during the time between S1and S2(0.5-4s) a slow negative shift develops over the central and frontal areasuntil the S2. This negative wave is called CNV. Oftenin the CNV an early and late phase can be distinguished. It is supposed that early CNV reflects orientation (O-wave) while the late is related to expectancy (E-wave). The idea that the E-wave is not just a motor potential (readiness potential) was proved by the fact that it appears without movement response too. ChangesinCNV can be observed in such psychopathologic cases when attention and stress responses are modified (depression etc.) Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials F:\scan\scan0006.jpg www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 29 EarlyCNV(orientingwave) LateCNV (expectancywave) (Warningstimulus) CNV WITHSHORTAND LONGS1-S2DELAY F:\scan\scan0005.jpg S1: auditoryclick S2: flashstimulus TasktoS2: fastbuttonpress Control: no task At4sS1-S2delaytheearlyand latecomponentsof CNV canbe recognized. The flatEOGindicatethattheCNV is notand eyemovementartefact. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 30 SUMMARYOF THECOMPONENTSOFTHE AUDITORYEVENTRELATEDPOTENTIALS logarithmictimescale!!! Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 31 AUDITORY STEADY-STATE RESPONSE (ASSR) Steady-state responses (SSR) are produced when stimuli are presented at a rate sufficiently rapid that the response to any one stimulus overlaps the responses to preceding stimuli. After the first few stimuli, the recorded potentials assume the periodic waveform of the steady-state response. Steady-state responses in most cases have sinus wave like pattern. Because of this they can be analysedin the frequency domain. In the auditory modality SSRappearsfrom around 40/s repetition rate (often called „40 Hz response”) but it can be elicited by repetitive stimuli at 80-120/s. The 40Hzresponse is generated in the auditory cortex while it is supposed that the higher frequency ASSRmay be generated in the brainstem. 40 Hz SSRis sensitive to sleep the whilehigher frequency SSRsare not. Auditory steady state responses are widely studied in the clinical audiology because this type of ERP can be used for objective audiometry. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials C:\Documents and Settings\gkarmos\Desktop\ssr.jpg www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 32 DEVELOPMENT OF ASSRIN CAT AUDITORY CORTEX ASSRsimilar to human one can be recorded in the auditory cortex of behaving cat with chronically implanted electrodes. Increasing of the rate of the click stimuli above 10/s the complex pattern of the evoked potential changes to a sinus like wave shape that has highest amplitude at 40/s rate. The 40 Hz ASSRis highly attenuated duringslow wave sleep. AWAKE SLEEP C:\Documents and Settings\gkarmos\Desktop\ssr.jpg Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 33 CLINICALAPPLICATIONOF THE ASSR In the following slides a technique called„MASTER” (MultipleAuditorySteady-StateResponses) will be shown that was developed by T.W.Pictonand M.S. John (RotmanResearch Institute, Baycrest, Ontario, Canada) for clinical audiometry purposes. This is a good example how the computer methods can be used in clinical diagnosis. picton Sasha John, PhDAssist Prof. Inst. Biomat & Biomed Engin., U. of Toronto Sasha John, PhDAssist Prof. Inst. Biomat & Biomed Engin., U. of Toronto G:\My Documents\oktatás\Picton\Sasha2.jpg Prof. Terence(Terry) W. Picton Univ. of Toronto RotmanResearch Institute Dr. Sasha John Univ.of Toronto Inst. Biomat& Biomed Engin. Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 34 CHARACTERISTICS OF ACOUSTIC SIGNALS The characteristic of the acousticsignal can be described by the FFT spectrum and the temporal pattern by the spectrogram. In the schematic figures characteristics of a pure tone, speechsignal andnoise signal are shown. This and the following figures bycourtesy of T.W. Pictonand M.S. John Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 35 CHARACTERISTICSOF BRAINELECTRICALRESPONSES The spectro-temporal characteristics of the brain signals can also be depicted. The SSR can be well described by the FFT. The first and second harmonics of the SSR is shown on the figure. ASSR can be elicited by repetitive clicks but for audiometric purpose amplitude modulated pure tone stimuli are the best. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 36 AMPLITUDE MODULATED TONE STIMULUS The left side of the next slide showshow an amplitude modulated tone stimulus is generated. 1000 Hz tone (called carrier frequency) is amplitude modulated by a lower frequency sine wave (85 Hz). The result will be an amplitude modulated (100%) 100 Hz stimulus. The ASSRelicited by a burst of such stimulus is shown on the right side of the figure. At the beginning of the stimulus a transient „on response” is elicited. Similarly at the end a transient „off response” appears. The SSRcontains a DC type „sustained response” and the real „steady-state response”that corresponds to the modulation frequency. In the ASSR audiometry the amplitude and phase characteristics of the SSR part of the response is measured. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 37 ASSRELICITEDBYAMPLITUDEMODULATEDTONESTIMULI www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 38 EVALUATIONOF THE SSR SSRcan be evaluated both intime domain (averaging) and in frequency domain (FFT). In the upper rows averaged responses (n: 1, 4, 16) and the FFTscalculated from the averages are shown. In the lower rows different trains of SSRand their FFTscan be seen. The frequency domain analysis gives betterquantitative result. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 39 ASSREVALUATIONINFREQUENCYDOMAIN Upper row shows original and averaged SSR(blue) and the phase and amplitude valueof f0harmonic of the FFT,depicted below. The phase and amplitude can be detected automatically and the stimulus presentation and averaging can be stopped when the amplitude exceeds agiven confidence limit. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 40 REPRESENTATION OF STIMULUS IN THE COCHLEA AND IN THE AUDITORY CORTEX The figures show that the amplitude modulated soundstimulus activates the basilar membrane at the site of the carrier frequencywhile in the brain stem and in the auditory cortex the ASSRis determined by thethemodulation frequency and theenergy of envelope. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 41 Reprinted bypremissionfromRotmanResearch Institute MIXING OF SOUNDS Different frequency and differently modulated sound stimuli can be mixed together. By frequency analysis the original patterns can be recovered. The cochlea is doing frequency analysis and the ASSRfrequency corresponds to the modulation frequency but its amplitude reflects the perceived stimulus intensity. This way with different intensity stimuli objective audiometry can be done if the theevoked ASSR-sareevaluated. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 42 ASSRRESPONSESELICITEDBYMIXED STIMULI The mixed four stimuli given through earphone to the ear elicit four ASSRcorresponding to the modulation frequencies.The phase amplitudeof the responses reflect the perceived tone intensities. The ASSRcan be used to estimate the audiogram of subjects who cannot respond accurately on behavioral testing, such as newborn babies or adults with a functional hearing loss. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 43 AUDIOMETRYBYASSRWITHSTIMULITOBOTH EARS Mixed stimuli can be given to both ears simultaneouslyif the modulating frequencies are different. In everyday audiometry the usually tested frequencies are 500 Hz, 1, 2, and 4 kHz. At a given intensity level all thesefrequencies can be tested in both ears simultaneously and automatically. This way ASSRaudiometry makes possible a fast and effective screening. R L www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 44 MASTER APPLICATIONS Auditory Steady State Response has been scientifically proven to provide valuable information on hearing thresholds, particularly in babies. On the principle shown above laptop based ASSR audiometers were introduced by different companies primarily for newborn hearing test. The ASSR is a good complement to the BAEP test. Its advantage that signal intensity can be as high as 120 dB HL. Electrodes are placed to Czand to the nape or to Czand the mastoid. The system automatically delivers the stimuli, makes the averaging and measuresthe signal to noise ratio at the modulation frequencies. As the S/N reachesa certain level the marker lights change from red (F-ratio of significance= >0.101) first to yellow (F-ratio of Significance= 0.051 -0.101), then to green (F-ratio of Significance= <0.050) and the stimulation stops. The total test can be performed in 45-60 min. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 45 Averaged FFTof the incoming signal; the eight bars show the values at the modulation frequencies. Audiogram graph for the right ear. Marker lights for the right ear stimuli. Parameters for the right ear. Incoming EEG signal. Parameters of the stimuli. Audiogram graph for the left ear. Marker lights for theleft ear stimuli. Parameters for the left ear. ONE OF THE DISPLAY SCREENS OF MASTER II www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 46 COMPARISON OF THE BEHAVIORAL AND ASSRAUDIOMETRY On the left side of the figureFFTharmonics of the ASSRis shown at different sound intensities. On the right side behavioral audiometry curves are compared with the result of the MASTER ASSRaudiometry. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 47 COMPARISON OF THE BEHAVIORAL AND ASSRAUDIOMETRY The good correlation between the behavioral and physiological (ASSR) thresholdsprovedthat the ASSRobjective audiometry can be used for testing hearing of newborns. Recently commercialsystems were introduced for this purpose. www.itk.ppke.hu Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-Related Potentials 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 48 www.vivosonic.com vivo baby full wires2 COMMERCIALLYAVAILABLEASSRSYSTEMS www. natus.com Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 49 REVIEWQUESTIONS What is the difference between the evoked potentials and the event related potentials? Which components of the evoked potentials are called exogenous? What is the difference between the exogenous and endogenous components? Why and how is averaging used for the study of human event related potentials? What is the clinical relevance of the brainstem auditory evoked potential? List the examples of the use of ERPsin cognitive psychophysiology. What is the „mismatch negativity” ERP component? How is selective attention reflected in N100component? What is P300component? Which are the language related ERP components? How is motor preparation reflected in the brain electrical activity? What is „contingent negative variation”? How is the auditory steady state response used in the clinical practice? Electrophysiological Methods For The Study Of The Nervous-And Muscular-systems:Event-RelatedPotentials www.itk.ppke.hu 2011.10.07.. TÁMOP –4.1.2-08/2/A/KMR-2009-0006 50 References Regan, D.: Human Electrophysiology.EvokedPotentialsand EvokedMagneticFieldsinScience and Medicine, Elsevier, Amsterdam, 1989. CacioppoJ.T., Tassinary, L.G., Berntson, G.G.: Handbookof Psychophysiology, Cambridge Univ. Press, 2000. Handy, T.C. (ed.): Event-RelatedPotentials: A MethodsHandbook, pp. 416, MIT Press, Cambridge, 2004. Luck, L.J.: An IntroductiontotheEvent-RelatedPotentialTechnique(CognitiveNeuroscience), pp. 376, MIT Press,Cambridge, 2005. Niedermayer, E., LopesDa Silva, F., (eds): Electroencephalograhy: Basic Principles, ClinicalApplications, and RelatedFields, (5thed.) LippincottWilliams and Wilkins, Philadelphia, 2005. Ebersole, J.S., Pedley, T.A.: CurrentPracticeof ClinicalElectroencephalography, LippincottWilliams and Wilkins, Philadelphia, 2003. JohnMS, PictonTW. MASTER: a Windows program for recording multiple auditory steady-state responses.Comput.Methods Programs Biomed. 2000,61:125-150. http://www.hearingreview.com/issues/articles/2007-11_03.asp http://www.natus.com/documents/MASTER-II_006572A.pdf