Understanding Event-Related Potentials and Cognitive Impairments in Schizophrenia

Hello and welcome to the course basics of experimental design for cognitive psychology. I'm Arma from the department

of cognitive science at ID Kpur. We are in week eight of the course and we are discussing event related

potentials. Now in most cases ERPs actually originate

as post synaptic potentials which occur when neurotransmitters bind to receptors changing the flow of ions across the

cell membrane. We're basically in this lecture going to talk a little bit about where do these ERPs arise from where

what is the source of this electrical activity that we are seeking to measure and then we are seeking to make it

contingent to uh you know stimulus processing within the brain. So the idea is that these ERPs actually are

postinaptic potentials which occur when the neurotransmitters are binding to uh receptors and they change the flow of

ions across the cell membrane. The ERPs recorded at the scalps are not really produced typically by action potentials

except in case of auditory responses that occur within a few milliseconds of the onset. When PSPs or postsaptic

potentials occur at the same time in large numbers of similarly oriented neurons they summit they are together

and are basically conducted at nearly the speed of light throughout the brain. So the traverse throughout the brain the

meninges the skull and the scalp. Thus ERPs are actually able to provide a direct instantaneous millisecond

resolution measure of the neurotransmitter mediated neural activity. So that is basically what we

are measuring as ERPs. Now when a post enaptic potential occurs within a single neuron, it creates a

tiny electrical dipole and oriented flow of current. And these measurable ERPs can be recorded at the scalp only when

the dipole from many thousands of similarly oriented neurons are put together or they are summed together.

Now if the orientations of the neurons in the given region are not similar to each other then dipoles then the dipoles

will all cancel out and will be impossible to detect at a distant electrode. But if they are oriented to

the same direction. So the main neurons that have this property are pyramidal cells of the cerebral cortex uh which

are the primary input output cells of the cortex. These cells are all oriented in a perpendicular direction to the

cortical surface and their dipoles therefore they add together and instead of canceling out. So that is the

activity that we can catch at the electrodes placed on the scalp. As a result, scalp recorded ERPs almost

always reflect the neurotransmission that occurs in their in the cortical parameal cells. Uh and basically what

happens is that the in non- laminina structures such as the basal ganglia etc. they do not typically generate ERPs

that can be recorded from the scalp and inter neurons within the cortex are thought to generate almost little to no

scalp ERP activity. So only the fraction of brain activity actually leads to detectable brain activity u uh you know

in the scalp or detectable ERP activity in the scalp. Now ERP components just to sort of

understand them can be either positive or negative at a given electrode site. The polarity depends on the combination

of factors. Say for example it is usually impossible to draw conclusions from the polarity of an ERP component.

So you cannot really uh you know make a lot of sense of whether a particular component is negative such as the N400

component which uh you know comes over in reaction to sentences like he spread with he spread his bed with warm socks.

So when there is a semantic anomaly uh this negative n400 component comes in it is basically a component that peaks at

400 mconds in the negative direction. Uh similarly we were talking about the P300 component in the last lecture which is a

positive component peaks at around 300 milliseconds and it basically is in response to the unpredictability of the

stimulus. So that P300 is positive and that N400 is negative. Uh the positive and negative part of the component does

not provide us much information. That is not typically what plays into the in inference or interpretation of these

components. Now when the dipoles from many individual neurons sum together, they

can be represented quite accurately within a single equivalent current dipole which becomes the vector sum of

all of these individual dipoles. If they are all summing together, they are oriented in the same direction. The

voltage recorded on the surface of the scalp will be positive on one side of the dipole and will be negative on the

other side with a single line of zero voltage separating the positive and negative sides. Now this voltage field

spreads out through the conducive medium of the brain and the high resistance of the skull and the low resistance of the

overlying scalp uh leading to further blurring. So it sort of blurs out uh you know uh over the scalp. Thus the voltage

for a single dipole will be fairly broadly distributed over the surface of the scalp especially for ERPs that are

generated in relatively deeper cortical structure. So that is why the signal is relatively weak and it needs to be

amplified. Okay. So we'll take one one more example uh an example of impaired cognition and

schizophrenia that will basically tell us a little bit about how ERP components are used to isolate specific uh

cognitive processes in the brain. Okay. So this experiment aims to ask why behavioral reaction times are typically

slowed down in schizophrenia patients when they are asked to perform simple sensory motor tasks. Now in these

patients artis uh you know could be slow down because of an impairment in perceptual processes or an impairment in

decision making or an impairment in the response selection process. So we basically are interested using ERP to

know what is it that is causing the slower reaction time responses and we are basically studying it through the

ERP methodology. Now ERPs are ideally suited for answering this question because they provide a direct means of

measuring the timing of the processes that occur between the stimulus presentation and the final response.

Now as for previous research experimenters hypothesized that the slowing of the reaction times in

schizophrenia in simple tasks simply does not result from the slowed perception or decision making but it

instead it results from an impairment in the process of determining which response is the appropriate one and the

uh you know once the stimulus has been perceived and categorized. So it is it seems that this slowness of response is

basically due to the time that is taken by the participants by the schizophrenic participants in deciding the appropriate

response in the response selection process. All right. So this is the hypothesis that they went in with to

test this hypothesis. The experimenters recorded from 20 individuals with schizophrenia and 20 healthy control

subjects in a modified oddball kind of task. In each 5-minute block of trials, the experimenters presented a sequence

of letters and digits at fixation. Each stimulus was presented for a duration of 200 milliseconds with a stimulus

appearing at every 1300 to,500 milliseconds. Here, subjects were asked to make a

button press response for each stimulus that they see, pressing with one hand for letters and with the other hand for

digits. Now, one of these two categories was rare. Remember the oddwell paradigm? So one category is rare. So one of these

two categories was rare and the other was frequent. So one came around 20% of the time and the other came around 80%

of the time in any given block of trials. Both the category probabilities and the assignment of hand to categories

were counterbalanced across trials. So sometimes the letters will come 20% and the digits will come 80%, sometimes the

digits will come 20%, letters will come 80%, sometimes you have to respond with right hand to the digit. sometimes you

have to respond with left hand to the digit. All right. So these things were counterbalanced across the experimental

block. Now such a design allowed the experimenters to isolate the specific

ERP components by means of difference waves wherein ERP waveforms elicited by one trial type let's say digits was

subtracted from the ERP waveform elicited by the other trial type let's say letters much like the difference uh

images that we do in fMRI etc. Now difference waves are extremely useful in ERP research because they isolate uh

neural processes that are differentially active for the two trial types. It basically tells us how the brain is

separately processing the digits and how the brain is separately processing the uh letters. It eliminates the many

concurrent concurrently active brain processes that do not differ between these two trial types. Okay. Now this is

important because the different ERP components are uh you know ordinarily they are all mixed together and it makes

it difficult to determine exactly which component uh which psychological or neural process

differs across these different conditions or groups. So basically what happens is the difference waves can pull

out a subset of components making it possible to draw more specific conclusions.

This is where you can see this is the rare uh uh wave. So you can see the rare P3 is obviously higher uh as opposed to

the frequent P3. And you basically compute a difference wave. So this is the rare minus frequent difference wave

for P3. And this is what you can see. This is typically what is happening in the control subjects with the solid line

and this is slightly subdued or attenuated in the patients. So this is the rare P3. This is the frequent P3.

You can see the rare minus difference. frequent rare minus frequent difference wave and you can see that the waves or

the effects are different for uh control subjects compared to the patients. So in the current study the rare minus

frequent difference waves were constructed to isolate the P3 wave which is the you know the one that we're

looking for in a nball paradigm which basically tells us about the time course of the stimulus categorization. Okay

that is the time it take uh the time it took the process of determining whether the stimulus falls into the rare or

frequent category alphabets or letters category sorry a letters or digits category. Another set of difference

waves was constructed to isolate the lateralized readiness potential. So this is another component that we are finding

or looking for here which reflects the time course of response selection after stimulus has been categorized after you

have decided that this is a letter or this is a digit. Okay. Uh now this LRP is also isolated by subtracting the

voltages over the ipsilateral hemisphere on the same hand uh from the voltages from the contrlateral hemisphere the

other hand. The experimenters found here that the RTS were slowed by approximately 60

milliseconds in patients as compared to control subjects. And the question was whether this uh you know uh this slowing

reflected a slowing of perception and categorization or whether it reflected the slowing of postcategorization

response selection process. Now the figure 1.4 basically shows this one. The figure 1.4 basically shows us that there

is a slight difference here. Okay. The ERP elicited by the rare category. The ERP is elicited by the frequent category

and the rare minus frequent categories. We saw those three and these are the grand average waveforms which basically

are first computed across trials for each subject at each electrode site and then these waveforms at each uh

electrode side average across subject. So that is why they are called grand average waveforms. These grand average

waveforms basically make it easier to look at the data. So this is across trials for a particular subject and then

average across subjects. So this is what is called the grand averaged uh waveforms.

Now as with previous uh studies the voltage during the period of P3 wave approximately that happens between 300

to 800 millconds was reduced in this schizophrenia group as we just saw uh group relative to the control group.

However the voltage during this period in is uh the sum of many different components and it is not just uh that of

the P3 wave. the rare minus frequent wave difference wave allows us to better isolate the uh P3 wave and to focus on

brain activity that reflects the classification of the stimulus as belonging to the different category or

the rare category or the frequent category. Now here you can see the patients exhibited no reduction in the

amplitude of the P3 wave in the difference waves. You can see here again the amplitude is pretty much similar for

the patients as well as the you know control subjects for the P3 wave in the rare minus frequent difference wave

condition. Okay. The most important finding here was that the timing of the P3 was

virtually identical in both patients and controls which indicates that the patients were being able to perceive and

categorize these stimuli just as fast as the control subjects even though we see later that their reaction times are

slower by 60 milliseconds. This slowing basically then it tells us that the slowing is not because of

perception and categorization differences but rather in response selection differences. So this implies

that the slowing of the RTS basically reflects an impairment in the processes that follow post stimulus

categorization. Indeed the LRP which is an index of response preparation was delayed by 75 milliseconds in the onset

time and it was much smaller. It was diminished by 50% in the amplitude for patients compared to control. So that's

a different analysis. Also the degree of amplitude reduction across patients was found to be significantly correlated

with the degree of RT slowing. So here now you can see how we can use reaction time how we can use the ERP

methodologies to understand procedurally or the mechanics of how uh the schizophrenic patients and why the

schizophrenic patients are slower in their behavioral responses uh when they are going through this oddball paradigm.

So for a relatively simple perceptual task, the slowed arts exhibited by the schizophrenia patients actually appear

to uh result from primarily from a slowing of response selection as evidenced by the later and smaller LRP

rather than the slowing of perception or categorization. This is a very good example of how we can use the ERP

methodology to understand the mechanics of particular processes. All right. So I'll stop here and I'll continue this

discussion on ERPs. basically looking at the various steps of ERP experiments in the next lecture. Thank you.