Indian J Physiol Pharmacol 2000; 44 (4) : 461-466

EVENT RELATED EVOKED POTENTIAL RESPONSESIN EPILEPTIC PATIENTS

O. P. TANDON* AND PRAVEEN DUHAN

Department of Physiology,University College of Medical Sciences & GTB Hospital,Shahdra, Delhi - 110 095

( Received on February 2, 2000 )

Abstract : The effect of epilepsy on cognitive functions has beeninvestigated in this study. The P300 auditory event related potentials(AERP), Wechsler Adult Performance Intelligence Scale (WAPIS - IndianAdaptation) & Digit Span Test (DST) have been used to assess the cognitivestatus. Twenty primary generalised epilepsy patients and 20 normalcontrols were subjected to WAPIS & DST testing and their AERP recorded.On comparative stahstica~ analysis, epileptic subjects were found to have

significantly higher N2 & P300 latencies and lower P300 amplitude, WAPIS­IQ scores & DST scores. These findings suggest that there is a generaldecline of cognitive functions in epileptics especially the memory, attention,concentration and speed of mental processing and as also corroborated byP300 and that P.300 can be used as an additional sensitive parameter toassess the cognitive status.

Key words : epilepsy cognitive functions P300 AERP

INTRODUCTION

Alteration of cognitive functions inepilepsy received particular attention from the19th century physicians who implied thatintellectual deterioration was an inevitablepart of epilepsy. Since that time there hasbeen fairly extensive discussion of intellectualchanges in epilepsy. A number of investigatorshave examined specific deficits in patientswith epilepsy including abnormalities ofmemory (1, 2, 3), perceptuomotor skills (4,5),speed of mental processing (6, 7) and attention(2, 8, 9) as well as overall impairments (asreflected by IQ scores etc.) of cognitive abilities(10, 11, 12).

In recent years, the P300 event relatedpotential has been used to assess cognitiveprocessing (13, 14). P300 latency reflects

*Corresponding Author

stimulus evaluation time (15) and is affectedby task difficulty (16). P300 amplitude isrelated to decision making, memory processingand task relevance (17). In this study, theP300 Auditory Event Related Potential hasbeen used as the electrophysiological tool toassess the cognitive status in epileptics andin addition, psychometric testing withWechsler Adult Performance Intelligence Scale(Indian adaptation of Wechsler AdultIntelligence Scale {WAIS} by P.Ramalingaswamy) (18) and the Digit Span'I'est has been carried out.

METHODS

Subjects: Twenty male patients of primarygeneralised epilepsy (newly diagnosedclinicaBy) of age 18-30 yrs were subjects ofthis study. Inclusion criteria 'were: a) No

462 Tandan and Duhan Indian J Physial Pharmacal 2000; 44(4)

The electrode recording sites on the scalpwere cleaned with spirit and skin pure.Electrolyte paste (Elefix) was applied and Ag/AgCI disc electrodes were anchored as per 10­20 International system of electrodeplacement:

evidence of progressive brain or systemicdisease, b) No previous exposure toantiepileptic drugs. AU patients had two ormore unprovoked seizure attacks. Seizureswere classified according to the revisedInternational Classification of EpilepticSeizures (19). The control group consisted ofage and sex matched 20 healthy volunteers.The controls and patients had comparablelevel of education (average: middle schoolpassed) and socioeconomic status. Bothpatients and controls were administered theWAPIS & DST and their AERP recorded. Eachsubject was included after a detailed physical& ENT examination.

P300 (AERP) : The subject was briefed about thetest procedure. He was made to sit on acomfortable chair in a soundproof airconditioned room. SMP4100 auditory/visualstimulator and MEB5200 NeuropackII evokedpotential recorder were used for AERPrecording. Standard auditory 'Odd Ball'paradigm was used. In this paradigm, thesubject was presented binaurally, throughheadphones, a sequence of two distinguishablesound click stimuli with differentcharacteristics. One occurred frequently (nontarO"et stimulus) and the other infrequentlyb

(target stimulus). The subject was asked torespond by pressing a button using hispreferred hand whenever a rare stimulus waspresented. The cerebral response obtained wasrecorded on the screen of the evoked potentialrecorder.

Active electrode (-): Vertex (Cz), MidlineParietal (pz)

Reference electrode (+): Both ears connected(AI + A2)

Grounding electrode: Forehead (Fpz)

The input impedance was kept below5 Kohms. Using shielded headphones,alternating tone bursts, with a startingcondensation phase of 10 msec rise/fall time,100 msec duration (plateau time), intensity70 dB NHL and rate 1 every 2 sec were usedas target stimuli. 80% of total 160 tones were1 KHz (frequent) and 20% were 2 KHz (rare).Stimulus sequence was random. The signalswere in phase at two ears. The MEB-5200setting were properly selected and evokedresponses to frequent and rare stimuli werefiltered with a band pass 5-30 Hz andaveraged simultaneously for 32 responses.Data obtained were stored, analysed andaveraged by the computer. The latency of N2,P300 and amplitude of P300 (recorded fromCz) for target stimulus was calculated. Duringthe recording session, the subject was askedto fix his eyes on a particular spot on theceiling in order to avoid electro-oculographicartifacts due to eye movem"ents and improvehis concentration and attention to the stimulipresented. The method used for recordingP300 was similar to the reported in ourlaboratory (13).

Psychometric tests: The Indian adaptationof WAIS by P. Ramalingaswamy and theDST wer~ administered to all patientsand controls. The original WAIS consistsof eleven subjects viz., information,comprehension, arithmetic, similarities, digitspan, vocabulary, digit sym~ol, picturecompletion, block design, picture arrangementand object assembly. Out of these, first sixform the verbal scale and the last five formthe performance scale. Due to the multilingualsociety in India and large illiterate population,the utility and applicability of verbal scale is

Indian ,J Physiol Pharmacol 2000; 44(4)

limited, therefore, the Indian adaptation ofWAIS by P. Ramalingaswamy consisting of theperformance scale of WAIS with slightmodifications to make it applicable to theIndian population was used. The performancescale IQ is a more sensitive indicator ofhigher function deficit than the verb alpart. The DST was included in the batteryof psychometric tests as it is a verysensitive test for immediate retention andrecall, attention and concentration. Bothforward and backward digit span testswere administered. WAPIS-IQ (intelligencequotient) scores and Digit Span scores werecomputed for each subject. A stop watch wasused to keep time during WAPIS and DSTadministration.

Event Related Evoked PotentFal Responses in Epilepsy 463

Data analysis: IQ scores for WAPIS,Digit Span scores, Latencies of N2 &P300 and P300 Amplitude were calculatedfor each subject. Comparisons of thesevariables between the epileptics andcontrol groups were made. The relationshipbetween IQ scores, Digit Span scores,N2 latency, P300 latency amplitudewas measured (Pearson's correlationtest). Scatter diagrams were plottedshowing correlation between thesevalues.

RESULTS

On comparative statistical analysis,following results were obtained:

TABLE I: Showing comparative data in two groups.

ControlsVa.riable (n = 20)

Mean SD

Age (yrs)• 2 (Lat) (ms)

P300 (Lat) (ms)P300 (Amp) (j.lV)

WAPIS Score (IQ)

Digit Span Score (max 28)

23.92204.00282.75

12.72109.33

23.08

3.7044.8023.96

3.568.511.08

Ef,ileptics P-ua.lucn =20) (T-test) SignijicrInce

Mean SD

22.83 3.95 0.496 Not Significant271.83 19.17 0.000 Significant348.17 22.05 0.000 Significant

8.33 1.73 0.001 Significant95.67 5.18 0.000 Significant18.67 1.07 0.000 Significant

r

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Fig. 1: Auditory event related potentials (P300) obtained from a representative subject from each group (a)Control Group (b) Epileptic Group. P300 recorded using aucjitory 'odd ball' paradigm. In (bl, N2 and P.300latencies are higher and P300 amplitude is lower.

464 Tandon and Duhan Indian J Physiol Pharmacal 2000; 44(4)

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Indian J Physiol Phannacol 2000; 44(4)

The mean P300 amplitude in controlswas 12.72 ± 3.5611V and in epilepsy patientswas 8.33 ± 1.7311V, a difference of 4.3911V,which is significant. The mean P300latency in epileptics (348.17:t 22.05 msec)was significantly higher than the meanP300 latency III the control group(282.75 ± 23.96 msec). The mean IQ scores(95.67 ± 5.18) and mean DST scores(18.67 ± 1.07) of epilepsy patients aresignificantly lower than the mean IQ scores009.33 ± 8.51) and mean DST scores(23.08 ± 1.08) of controls (Table 1). Figure 1shows the actual representative recordsof P 3 of control (a) and epilepticpatients (b). The latter dearly depictsincreased N z' P 3 latency and decreasedamplitude.

A significant negative correlation wasfound between IQ scores & P300 latency, DSTscores & P300 latency, IQ scores & N2 latencyand DST scores & N2 latency (Fig. 2).

DISCUSSION

Several groups of investigators havestudied the cognitive changes in epilepsy andthe results generaHy indicate (apart frominter-study variations) that there is a declineof cognitive functions in epileptics, especiallythe memory, attention, concentration andspeed of mental processing. Our results arein consonance with these observations. TheIQ scores and Digit Span scores of epilepticsin our study were significantly lower than thescores of control group.

The N2 & P300 latencies were significantlyhigher in epileptics than in controls and theywere negatively correlated with IQ and DSTscores. These results are also in agreementwith those of other similar studies (20, 21,22). Prolonged N2 & P300 latencies may

Event Related Evoked Potential Responses in Epilepsy 465

indicate disturbed information processing inthe brain as these cortical evoked potentialsare sensitive indices of cognitive functions.Much work has been done on P300 potentials(23, 24, 25), but N2, potentials have notreceived as much attention. N2 is a longlatency event related potential, normallyhaving a latency of -200 msec. It reflectsprocesses that playa causal role in detectionand discrimination. It is a sign of mismatchbetween an infrequent stimulus and apreceding series ·of background stimuli. N2actually consists of two separate components,one reflecting controlled processing i.e.occuring only for attended stimuli, and theother being a manifestation of automaticprocessing referred to as Mismatch Negativity(MMN) to emphasise its dependence onmismatch of a deviant stimulus and ahomogeneous background. P300 is a measureof controlled processing, i.e. processing thatis intentional and capacity limited. It reflectssubsequent memory storage processes thatenable the subject to use current informationto prepare for future events.

There are marked changes in EEG activityof primary generalised epilepsy patients. Highamplitude spikes and sharp waves of 10/secor higher frequency are seen during seizuresand in interictal period. The epileptogenic focimust be interacting with generators of P300residing in limbic areas of ternporal lobe,changing P300 characteristics, however exactmechanism of this interaction remains to beworked out.

The P300 amplitude did not correlate withIQ scores or with DST scores (although themean P300 amplitude of epileptic group wassignificantly lower than the control group), soP300 latency is more sensitive to cognitivechanges than the P300 amplitude.

466 Tandon and Duhan

From this study it can be concludedthat epilepsy does affect cognitive processingand causes decline of higher functions

Indian J Physiol Pharmacol 2000; 44(4)

especially recent memory and recall,attention, concentration and speed of mentalprocessing.

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