Event Related Potentials, Cognitive Evoked Potentials. These are stimulus unrelated potentials, which depend on the patient's ability to differentiate between a rare stimulus and a common stimulus.
2. • VEP, BAEP, SEP - stimulus related potentials (SRPs) / exogenous
potentials. Independent of whether the subject is attentive to or
interested in the stimulus. They can be recorded even when the patient
is asleep.
• Event related Potentials (ERPs) / Endogenous Potentials / Cognitive
Evoked Potentials - occur only when the subject is selectively attentive
to the stimulus. They are elicited only when the subject distinguishes
one stimulus (target) from a group of other stimuli (non targets).
3. SIMPLE EXPERIMENTAL MODEL OF ERP
• 2 stimuli given.
1. Frequent Stimulus (1000 hz tone)
2. Rare Stimulus (2000 hz tone)
• Subject is required to count mentally or respond to one of the two stimuli.
(by pressing on the remote) It allows the assessment of accuracy of
responses.
• Cerebral responses to the rare and frequent stimuli are recorded and
averaged separately.
4. • The response to frequent stimulus consists of a series of waves (stimulus related
components) that relates, for most part, to the sensory modality stimulated.
• For eg. to an auditory stimulus - the response has been divided into three
sequential time periods.
1. Early Latency response
2. Mid Latency response
3. Long Latency response
5. • Early latency response - (less than 10 ms) reflects the activity in the peripheral and brainstem auditory structures
• Mid Latency response - (between 10ms and 50ms) - thought to reflect a combination of muscle reflex activity and
neural activity that may arise in thalamocortical radiations, primary auditory cortex, early association cortex
• Long Latency response - (> 50ms) - uncertain generator. Probably reflects overlapping neural activity from
multiple neocortical and limbic regions. ( It has N1, and P2 components, has largest amplitude at the vertex,
hence aka Vertex Potential)
negative (N1)–positive (apparent P2)–negative (N2)–
positive (P3) complex (see Fig. 29-1). The first positive
wave is termed apparent P2 because it represents the
sum of the stimulus-related P2 and the event-related
P165. This response is quite consistent, in both ampli-
tude and latency, in the same subject performing the
same task14,22–24
even when measured on several differ-
ent occasions over a period of months (Fig. 29-4). The
approximately 300 to 400 msec following onset of the
rare stimulus; it is of positive polarity and is of maximal
amplitude in the midline over the central and parietal re-
gions of the scalp. An evoked potential component with a
similar scalp distribution can be recorded to stimuli in
any of the sensory modalities (see Fig. 29-3) and can even
be recorded (without associated SRPs) when an antici-
pated stimulus is omitted unexpectedly.5
The neural gen-
P2
N1
PO
NO
Na
Nb
Pa
I II
III
IV
V
VI
0 5 10 0 25 50
Latency (msec)
Early-latency
response
Mid-latency
response
Long-latency
response
0.06 !V
"
#
0.12 !V
"
#
0 400 800
2.5 !V
"
#
FIGURE 29-2 ¡ Evoked potentials
recorded from the vertex (Cz) in
response to an auditory stimulus dur-
ing three sequential time periods show
the early-latency (brainstem auditory
evoked potential), mid-latency, and
long-latency responses.
Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
6. • This long latency N1 P2 potential can be
elicited by auditory, visual and
somatosensory stimuli.
• Hence this Long Latency response is an
obligate response of the nervous system
to the stimulus and largely dependent on
the subject’s attention or level of arousal.
• This long latency N1 P2 response reflects
the activity in neural areas that can be
activated by more than one sensory
modality. (auditory, visual, somatosensory)
P2
P2
P2
P3
P3
P3
N1
N1
N1
N2
N2
N2
N1
N1
N1
0 400 800 0 400 800
Latency (msec)
Frequent stimulus Rare stimulus
5 !V
"
#
Auditory
Visual
Somatosensory
FIGURE 29-3 ¡ Long-latency potentials elicited by auditory
(top row), visual (middle row), and somatosensory (bottom
row) stimuli. The responses to rare and frequent stimuli in
each modality are shown. In each case, the frequent stimulus
elicited a negative (N1)–positive (P2) response, and the rare
stimulus elicited, in addition, an event-related response.
FI
ve
2-
th
“i
Fi
am
D
co
pe
Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
7. • Hence, Early latency responses (<10ms),
Mid Latency responses (<50ms), Late
latency responses (> 50ms) are all stimulus
related responses.
• But it was also found that the Long
Latency response which occurred to Rare
Auditory Stimulus was different and
consisted of N1, P2, N2, P3 complex.
P2
P2
P2
P3
P3
P3
N1
N1
N1
N2
N2
N2
N1
N1
N1
0 400 800 0 400 800
Latency (msec)
Frequent stimulus Rare stimulus
5 !V
"
#
Auditory
Visual
Somatosensory
FIGURE 29-3 ¡ Long-latency potentials elicited by auditory
(top row), visual (middle row), and somatosensory (bottom
row) stimuli. The responses to rare and frequent stimuli in
each modality are shown. In each case, the frequent stimulus
elicited a negative (N1)–positive (P2) response, and the rare
stimulus elicited, in addition, an event-related response.
FI
ve
2-
th
“i
Fi
am
D
co
pe
Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
8. • P165, N200, P300 responses were
found most consistent.
• P300 maximum amplitude seen
over central and parietal regions
of scalp. P300=P3
• Neural generators of P300 - not
known, evidence suggests it to be
of temporo-parietal origin.
• P300 was found at latency varying
from 250 - 600ms, mostly around
300ms.
P2
P2
P2
P3
P3
P3
N1
N1
N1
N2
N2
N2
N1
N1
N1
0 400 800 0 400 800
Latency (msec)
Frequent stimulus Rare stimulus
5 !V
"
#
Auditory
Visual
Somatosensory
FIGURE 29-3 ¡ Long-latency potentials elicited by auditory
(top row), visual (middle row), and somatosensory (bottom
row) stimuli. The responses to rare and frequent stimuli in
each modality are shown. In each case, the frequent stimulus
elicited a negative (N1)–positive (P2) response, and the rare
stimulus elicited, in addition, an event-related response.
P165
P300
N200
0 350 700
Latency (msec)
5 !V
"
#
FIGURE 29-4 ¡ Event-related potentials recorded from the
vertex in response to a rare tone on several occasions over a
2-month period in the same subject. Each trace represents
the difference waveform obtained by subtracting the rare-tone
“ignore” waveform from the rare-tone “count” waveform (see
Fig. 29-1). The event-related response is quite stable in both
amplitude and latency over time. (Modified from Goodin
DS, Squires KC, Henderson BH et al: An early event-related
cortical potential. Psychophysiology, 15:360, 1978, with
permission.) Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
9. • P300 is thought to be a sum of P3a and P3b.
• P3a - occurs slightly earlier, and has a more frontal distribution -
Independent of task relevance
• P3b - occurs slightly later, has more parietal distribution - Best
elicited by attending to task relevant stimulus.
10. RECORDING PARAMETERS
• It is necessary to be able to deliver both frequent and rare stimuli and to
average separately the cerebral response to each.
• Any stimuli can be used, Auditory stimulus is the most common.
• The stimuli are two or three different pitched tones. eg. Frequent stimulus -
1000 Hz, Rare stimulus - 2000 Hz. (Rare stimulus / Meaningful stimulus/ target
stimulus - is 15-20 % of frequent stimuli)
• The stimuli are delivered binaurally with a relatively long inter stimulus interval
(> 1 per second) because of long refractory period of the vertex potential.
11. • Optimally, multiple recording channels (minimum of 4)
are used.
• Responses are recorded from Fz, Cz, and Pz electrode
placements on the scalp referenced to an indifferent
scalp location like mastoids / ear lobes. Electrode
impedance - < 5 Kilo ohms.
• Eye movements may contaminate the ERP recordings,
therefore at least one channel usually is devoted to
monitoring them.
• Depending on the recording apparatus used, it may be
possible to reject automatically trials containing eye
movements or to remove digitally eye blink artifacts
from the responses obtained.
• Visual Cognitive Evoked Potentials - Frequent stimulus
- Blue squares, Infrequent stimulus - black squares.
Source - Clinical Neurophysiology, 3rd ed, UK Mishra and J Kalita
14. DONEC QUIS NUNC
Peak Latency,
Base to peak amplitude
Source - Clinical Neurophysiology, 3rd ed, UK Mishra and J Kalita
15. • Variables affecting the SRPs are different from those affecting the
ERPs.
• Eg. change in intensity of stimulation has relatively little effect on
P3 component, but has a major influence on the associated SRPs.
• P3 is influenced by the ease with which the targets can be
distinguished from non targets, by alterations in the ratio of targets
to non targets stimuli, or by shifts in attention of the subject
although converging evidence has suggested a temporo-
parietal source.15,25–30
Several variables alter the amplitude and latency of the
SRPs without appreciably affecting the ERPs, and vice
versa. For instance, a change in the intensity of stimula-
tion has relatively little effect on the P3 component
(Fig. 29-5) but has a major influence on the associated
SRPs (see Chapters 22 to 27). Conversely, the P3 is influ-
enced by changes in the ease with which targets can be
distinguished from nontargets (Fig. 29-6), by alterations
in the ratio of target to nontarget stimuli (Fig. 29-7), or by
shifts in the attention of the subject (see Fig. 29-1),
whereas SRPs are not.4,5,7,17,31–33
0 400 800
msec
10 !V
#
FIGURE 29-5 ¡ Event-related potentials recorded from the
vertex of a 30-year-old subject in response to rare auditory
stimuli of different stimulus intensities (measured in dB HL).
A reduction in stimulus intensity did not influence the ampli-
tude or latency of the P3 response (despite an increase in the
latency of the stimulus-related N1 component) until a stimulus
of 5 dB HL was used, at which point the stimuli were barely
perceptible to the subject.
P3
P3
N2
N2
P165
P165
0 400 800
Latency (msec)
5 !V
20 dB
3 dB
"
#
FIGURE 29-6 ¡ Event-related potentials (ERPs) (plotted
y of the
nd vice
timula-
ponent
ociated
is influ-
can be
erations
7), or by
29-1),
er both
tely the
ity can
stimu-
two or
elivered
nterval
N2
0 400 800
Latency (msec)
5 !V
"
#
FIGURE 29-6 ¡ Event-related potentials (ERPs) (plotted as
difference waveforms: see Fig. 29-1) obtained from two sub-
jects at two different levels of task difficulty. In the easy condi-
tion (solid lines) the subjects were required to distinguish two
tones that differed in intensity by 20 dB, whereas in the diffi-
cult condition (dashed lines) the two tones differed in intensity
by only 3 dB. The peak latencies of the different components
of the ERP are longer in response to the difficult task than to
the easy one. (Modified from Goodin DS, Squires KC, Starr
A: Variations in early and late event-related components of
the auditory evoked potential with task difficulty. Electroence-
phalogr Clin Neurophysiol, 55:680, 1983, with permission.)
Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
16. 1. AGE
FACTORS INFLUENCING ERPS
• In early age, children - P3 latency
is prolonged, as cognitive
development takes place, they
reach adult latencies by teenage/
early twenties.
• Thereafter, gradual increase in
P3 latency occurs.
age(seeFig.29-9andTable29-1).Severalstudieshavecor-
roborated these general findings (Table 29-2), although the
rate of these changes has varied somewhat between re-
ports.22,36,39–49
Althoughoccasionalreportshavesuggested
that the age-related change in the latency of the P3 com-
ponent is curvilinear,43
most authors have found the
P3 latency–age function to be linear.16,36,40–42,44,45
For
example, in a meta-analysis of the existing literature on
this issue as of 1996, Polich concluded that the weight of
the evidence supported a linear, and not a curvilinear, re-
lationship between the latency of P3 and age.42
This has
continued to be the experience of others.44,45,47–50
As a re-
sultofthesediscrepancies,itisunclearwhether,orinwhat
circumstances, nonlinear factors are important determi-
nants of the P3 latency–age function. For example, even
in the study of Anderer and associates,43
the significance
of such curvilinear effects may have been exaggerated by
the fact that the four oldest subjects (greater than 80 years)
had quite deviant P3 latencies. It would be of interest to
know what effect the exclusion of these four subjects from
the analysis may have on the significance of the curvilin-
earnature oftheage–latencyfunction.Inaddition,there-
sults of one study,49
in which a high level of cognitive
function was strictly controlled, indicated that there were
no significant age-related changes in either P3 latency or
amplitude. Although this study has been criticized,50
the
findings are provocative and clearly worth replication.
Regardless, however, even based on this study, when
using a specific testing procedure on individuals of uncer-
P3
0 10 20 30 40 50 60 70 80
460
420
380
340
300
260
N2
360
320
280
240
200
160
P2
N1
140
100
60
240
200
160
120
Age (years)
Latency
(msec)
Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
17. 2. SEX
• Affects the ERPs less as compared to the SRPs.
• Although amplitude of P300 may be larger in females.
18. 3. DRUGS
• Unchanged with antipsychotics. As proven by multiple studies.
• Several authors have reported significant Increase in amplitude, decrease in P3
latency in Alzheimers disease patients, after being treated by Anti-cholinesterase
drugs
• These changes are not because of the effect on generators of P3 per se, and may
result from a general change in attention or arousal of the subject.
• Opposite effect has been noticed with use of anti cholinergic medications
• AED - P3 latency unchanged in Valproate, CBZ, but was increased with
Phenobarbitone.
19. 4. SLEEP DEPRIVATION
• Increase in latency, decrease in amplitude of P3 response,
• Reflecting the subject’s level of vigilance, in the sleep deprived state.
20. 5. FITNESS
• Moderate exercise has been reported to reduce P3 latency in older patients.
• Following exercise this happened, but was not significant when fit and sedentary
subjects were compared.
21. 6. ATTENTION
• Decrease in alertness - reduction in amplitude.
• Drowsiness or inattention - decreases P3 amplitude and may
even obliterate it.
22. 7. TASK
• The latency of P300 increases as the discrimination of the task
becomes harder.
23. CLINICAL APPLICATIONS
DEMENTIA
In patients with dementia, P3 latency is prolonged, amplitude is
shortened.
ERPs are sensitive to task variables, that relate to cognitive
behaviour
Many studies showed, prolonged P3 latency (significant), amplitude
was also reduced, but because of its large normal variability, it
could not be used to distinguish between normal patients and
dementia patients.
24. .
e
-
h
y
s
-
.
-
d
d
d
-
t
-
n
N1
0 400 800 0 400 800
msec
5 !V
"
#
FIGURE 29-10 ¡ Long-latency evoked potentials recorded
from the vertex in two subjects of similar age, one of whom
was demented. The top row shows the response recorded from
the demented subject. The bottom row shows the response
recorded from the normal subject. The waveforms on the left
are the responses to the frequent tone and those on the right
are to the rare tone. The latency and amplitude of the N1 and
P2 components are similar in the two subjects, but the later
event-related components are small and delayed in the re-
sponse from the demented subject. (From Goodin DS: Elec-
trophysiologic evaluation of dementia. Neurol Clin, 3:633,
1985, with permission.)
and Psychiatric Disease: Percentage Abnormality*
Psychiatric Patients Nondemented Patients
3% (33){
4% (51){
}
eemed likely that they might be altered in patients
h disorders of cognition such as dementia. Indeed,
eral groups have studied the P3 component in de-
nted patients and reported that it is of prolonged la-
cy and reduced amplitude in this group (Fig. 29-10
dTable29-3).36,72–85
Forexample,inonestudyof58de-
nted patients, the P3 latency was more than 2 standard
ors above the normal age–latency regression line in 74
cent of patients (Fig. 29-11).36
Moreover, with the ex-
tion of a single patient who had a profound postence-
alitic anterograde amnestic syndrome without other
nitive difficulties, all diagnostic categories of dementia
wed similar prolongations in P3 latency (Table 29-4).
e P3 amplitude was also reduced significantly in the
up of demented patients but, because of its large nor-
l variability, amplitude could not be used to distinguish
ividual patients from normal control subjects.36
By
ntrast, only 3.5 percent of the 84 nondemented patients
h diverse neurologic and psychiatric disorders had P3 la-
N1
N1 N1
N1
N2
N2
P2 P3
P3
P2
0 400 800 0 400 800
msec
Frequent tone Rare tone
5 !V
Demented
subject
Age 58
Normal
subject
Age 64
"
#
FIGURE 29-10 ¡ Long-latency evoked potentials recorded
641
Event-Related Potentials
Source - Aminoff’s Electrodiagnosis in Clinical Neurology 6th ed.
25. • ERPs may be used to diagnose Mild Cognitive Impairment.
• Baseline P300 latency, may be used to predict the conversion of Mild Cognitive
Impairment to Dementia.
• May be used to detect the component of Dementia in Parkinsons, Huntingtons
Chorea etc.
• One of the studies, showed relation between baseline P300 latency and the risk of
experiencing difficulties in ADL.
26. MULTIPLE SCLEROSIS
• Cognitive dysfunction is being increasingly recognised in MS.
• Prolonged P300 may be due to the cognitive dysfunction occurring in MS, or it may
be due to Demylination of any of the afferent tracts in the subcortical region.
• Aminoff and Goodin found that due to Demylination - only the absolute latencies
N1, P2, N2, P3 were delayed.
Where as in the case of cognitive dysfunction - N1 - N2, N1 - N3 inter peak latencies
were both delayed and correlated with patients’ level of cognitive function.
27. HIV
• It was found that 1/3rd of asymptomatic HIV patients, had ERP changes similar to
that of over dementia, suggesting that these patients were at risk for developing
cognitive abnormalities.
• Thus it may be that recording of ERPs may permit early recognition of HIV
encephalopathy, and identify patients with a poor prognosis.
• It was also found, that once started on HAART, the P3 latency shortened.
• P3 latency correlated inversely with CD4 count. (Higher CD4, shorter P3 latency).
36. • P50 - most positive peak between 40 - 75 ms after a frequent stimulus is delivered -
reflects individuals ability to selectively attend to salient stimuli and ignore the redundant
stimuli, protecting the brain from information overflow.
• N100 or N1 - negative deflection between 90 - 200ms. Occurs when infrequent/rare/
target stimulus is delivered.
• P200 or P2 wave - positive deflection around 100-250ms.
• Current evidence suggests N1 P2 component reflects sensation seeking behaviour of
individual.
• P600 - in the domain of language processing, P600 effect occurs to sentences that contain
syntactic violation or a complex syntactic structure.
Source- Sur S, Sinha VK. Event-related potential: An overview. Ind Psychiatry J. 2009;18(1):70-73. doi:10.4103/0972-6748.57865
