Name: investigating the effects of antipsychotics and schizotypy on the n400 using event-related potentials and semantic categorization
Uploaded: 2014-11-19T15:00:00
Duration: 12 min
Description: Watch this Scientific Journal Video about Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization at JoVE.com

The authors would like to acknowledge the Brain and Behavior Research Foundation for their generous support.

This protocol follows the guidelines set forth by the Douglas Institute Research and Ethics Board.
1. Patient Preparation
<ol>
	<li>When the participant arrives, explain the experiment and obtain a signature on an informed consent form that has received ethics approval from the institutions&#8217; Institutional Review Board.</li>
	<li>Make a mark using the red pencil at the bridge of the nose (nasion), in between the eyebrows. Using a tape measure, measure from the nasion to the lower base of the skull, the inion. Discern this location by sliding a hand up the neck until a bump on the back of the participant&#8217;s head is felt.</li>
	<li>Take 1/10th of the measurement between the nasion and the inion and make a mark up near the hairline from the nasion, taking care to ensure that these measurements are in line with the nose.</li>
	<li>Wrap the Head Measuring Tape (4 Color ribbon) around the head at the level of the mark made in Step 1.3. Determine cap size based on where the non-colored end of the ribbon meets the colored end: use a blue cap if it crosses in the blue region, use a blue-red cap if it crosses between the blue and red regions, etc.</li>
</ol>
2. Electrode Placement
<ol>
	<li>Place the cap onto the participant&#8217;s head. Line up the two electrodes at the front of the cap with the eyes. Insert the disposable sponge disks on the frontal electrodes (FP1 and FP2), to keep the electro-gel from spreading.</li>
	<li>Hold the two frontal electrodes against the mark near the hairline and pull the cap over the head. Ensure that the cap fits snugly on the participants head.</li>
	<li>Place the ear electrodes onto the participant&#8217;s earlobes as reference electrodes. Clean the earlobes with alcohol. Using a cotton tip applicator, spread EEG abrasive skin prepping gel onto the earlobes to facilitate conductivity.</li>
	<li>Take a syringe and fill it with electrolyte gel. Then, squeeze the gel onto the ear electrode. Carefully place the gel-filled ear electrode onto the participant&#8217;s earlobes.</li>
	<li>Attach the wires from the cap and the ear electrodes to the EEG amplifier. Set the gain of the amplifier to 20,000. Attach the harness to the cap with the cap straps, making sure that it is snugly keeping the cap in place.</li>
	<li>Start applying electrolyte gel to the ground electrode, which is found in the middle anterior of the cap. Electrolyte gel increases the electrical connectivity between the scalp and the electrode.</li>
	<li>Use the syringe to squeeze electrolyte gel into the electrode. Start by inserting the syringe into the electrode and rock it back and forth until it is in contact with the scalp. Then, simultaneously squeeze the syringe and pull up, creating a vertical column of gel.</li>
	<li>Repeat Step 2.7 for all of the electrodes.</li>
	<li>Abrade the scalp underneath the electrodes with a blunt needle. Do this while observing the computer monitor, which should display a schematic of the electrodes. Aim to scratch the scalp until the corresponding electrode on the screen turns black in color. It is recommended to start with the ear electrodes, and then move on to the ground electrodes.</li>
</ol>
3. Electroencephalography EEG Experiment
<ol>
	<li>Read the instructions for the experiment to the subject. Open the EEG acquisition software on the computer.</li>
	<li>Observe the resting activity of the electrodes. Troubleshoot for &#8220;bad&#8221; electrodes, such as flat line signals, or excessively active signals. If there are any, repeat Steps 2.7 and 2.9 to minimize impedance. 
	strong&#62;NOTE: The impedance, which is measured using a 30 Hz current, should be kept below 5 k&#8486;.</li>
	<li>Begin recording once the electrode signals look good and there are no flat line signals or excessively active signals. Look for any myograms or eye movement, and ensure that the participant refrains from blinking and tensing their jaw and forehead muscles, as these will produce excessive noise in the data. At rest, there may be beta and alpha rhythms present.</li>
	<li>Start the experiment on the second computer. The timing of the experimental design is important. Observe carefully to ensure that the experiment software, such as E-Prime, sends &#8220;markers&#8221; to indicate stimulus onset. This is crucial as stimulus onset is often used as a reference point for an event in ERP paradigms.</li>
	<li>Once the experiment is complete, ensure that the data has been saved- this process will differ depending on the software used. Carefully remove the cap, and assist the participant with hair washing and drying.</li>
	<li>Detach the cap and ear electrodes from the amplifier, remove the disposable sponge disks, and clean the cap and ear electrodes under running water using a stick or the end of a cotton swab. Use a mild soap or shampoo, as well as a toothbrush, to gently clear the gel from the electrodes. Rinse thoroughly. Allow the equipment to air dry.</li>
</ol>
4. Data Processing
<ol>
	<li>To obtain ERP components from the EEG, determine which epoch will be studied. For example, to compute the N400 amplitude, use the mean voltages in the 300-500 msec time-window for calculation.</li>
	<li>Before averaging the EEG epochs, reject trials with excessive eye movements or amplifier saturations. Depending on the experiment paradigm, it may be relevant to reject trials that correspond to incorrect responses.</li>
	<li>After averaging, filter the ERPs and plot the data (see Animated Figure 1 for specific instructions on data processing using Matlab, EEGLab, and ERPLab).</li>
</ol>

<ol>
	<li>Debruille, J. B., Rodier, M., Prevost, M., Lionnet, C., Molavi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+a+small+dose+of+olanzapine+on+healthy+subjects+according+to+their+schizotypy:+an+ERP+study+using+a+semantic+categorization+and+an+oddball+task.">Effects of a small dose of olanzapine on healthy subjects according to their schizotypy: an ERP study using a semantic categorization and an oddball task.</a> Europeam Neuropsychopharmacology. 23 (5), 339-350 (2013).</li><li>Bressler, S. L., Arbib, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Handbook of Brain Theory and Neural Networks. , 412-415 (2002).</li><li>Peterson, N. N., Schroeder, C. E., Arezzo, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+generators+of+early+cortical+somatosensory+evoked+potentials+in+the+awake+monkey.">Neural generators of early cortical somatosensory evoked potentials in the awake monkey.</a> Electroencephalography and Clinical Neurophysiology. 96 (3), 248-260 (1995).</li><li>Blackwood, D. H., Muir, W. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+brain+potentials+and+their+application.">Cognitive brain potentials and their application.</a> The British Journal of Psychiatry Supplement. 9, 96-100 (1990).</li><li>Debruille, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+N400+potential+could+index+a+semantic+inhibition.">The N400 potential could index a semantic inhibition.</a> Brain Research Reviews. 56 (2), 472-477 (2007).</li><li>Kutas, M., Hillyard, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A.Event-Related+Brain+Potentials+(ERPs)+Elicited+by+Novel+Stimuli+during+Sentence+Processing.">A.Event-Related Brain Potentials (ERPs) Elicited by Novel Stimuli during Sentence Processing.</a> Annals of the New York Academy of Sciences. 425 (1), 236-241 (1984).</li><li>Holcomb, P. J., Kounios, J., Anderson, J. E., West, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-coding,+context-availability,+and+concreteness+effects+in+sentence+comprehension:+an+electrophysiological+investigation.">Dual-coding, context-availability, and concreteness effects in sentence comprehension: an electrophysiological investigation.</a> Journal of Experimental Psychology: Learning, Memory, and Cognition. 25, 721-742 (1999).</li><li>Renoult, L., Brodeur, M. B., Debruille, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Semantic+processing+of+highly+repeated+concepts+presented+in+single-word+trials:+electrophysiological+and+behavioral+correlates.">Semantic processing of highly repeated concepts presented in single-word trials: electrophysiological and behavioral correlates.</a> Biological Psychology. 84, 206-220 (2010).</li><li>Prevost, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Schizotypal+traits+and+N400+in+healthy+subjects.">Schizotypal traits and N400 in healthy subjects.</a> Psychophysiology. 47, 1047-1056 (2010).</li><li>Sur, S., Sinha, V. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Event-related+potential:+An+overview.">Event-related potential: An overview.</a> Industrial Psychiatry Journal. 18 (1), 70-73 (2009).</li><li>Condray, R., Siegle, G. J., Cohen, J. D., van Kammen, D. P., Steinhauer, S. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automatic+activation+of+the+semantic+network+in+schizophrenia:+evidence+from+event-related+brain+potentials.">Automatic activation of the semantic network in schizophrenia: evidence from event-related brain potentials.</a> Biological Psychiatry. 54, 1134-1148 (2003).</li><li>Condray, R., Steinhauer, S. R., Cohen, J. D., van Kammen, D. P., Kasparek, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulation+of+language+processing+in+schizophrenia:+effects+of+context+and+haloperidol+on+the+event-related+potential.">Modulation of language processing in schizophrenia: effects of context and haloperidol on the event-related potential.</a> Biological Psychiatry. 45, 1336-1355 (1999).</li><li>Light, G. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electroencephalography+(EEG)+and+event-related+potentials+(ERPs)+with+human+participants.">Electroencephalography (EEG) and event-related potentials (ERPs) with human participants.</a> Current Protocols in Neuroscience. , 21-24 (2010).</li><li>Luck, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> An Introduction to the Event-Related Potential Technique. , (2005).</li><li>Luck, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> An Introduction to the Event-Related Potential Technique. , (2005).</li></ol>

The authors have nothing to disclose.

In our investigation of the effects of antipsychotic medication on the N400, we found that in the placebo condition, anterior N400s were larger in individuals with high schizotypy than in the subjects with low schizotypy. In the medication condition however, fronto-central N400s were smaller, but only in the individuals with high schizotypy. Thus, the medication was seen to decrease these large fronto-central N400s in high schizotypal individuals, which confirms previous research illustrating smaller anterior N400s in schizophrenic patients treated with antipsychotic medication, relative to patients receiving a placebo11,12. In individuals with low schizotypy, there was no effect of medication. These findings were obtained with the proper implementation of the protocol, and speak to the importance of collecting clear and precise data.
To ensure accurate and valid results, there are a few critical points to keep in mind. To get a good signal, it is crucial that the cap is snugly fit and placed so that the sagittal electrodes are exactly in the middle and that impedance is adjusted. A cap that is too large can reduce the recording quality, as it will be much harder to reduce impedances13. It is also important that the participants understand that they must avoid excessive movement, blinking, or flexing their face and jaw muscles, as these actions will introduce changes in the EEG traces and potentially make data interpretation very difficult14. After the experiment, the equipment must be properly cleaned to ensure that the electrodes are not blocked with gel residue, which could affect future signal collection.

If there are problems in the signal, such as noise or flat lines, check to make sure that both the ground and reference electrodes are properly connected. Reducing the impedance of these electrodes can reduce noise, so if there are problems in the connectivity, reapply the gel and re-scratch the scalp underneath the electrodes. If there are myograms, allow the subject to relax before proceeding. In designing the experiment, it is relevant for ERP recording that the experimental design accounts for timing aspects, such as the duration of stimulus presentation and brief time periods that allow the participant to blink.

Before beginning an EEG experiment, it is important to understand the associated limitations. The relatively poor spatial resolution may be something to consider, as well as the difficulty of using EEG to elucidate subcortical activity. The noise introduced by blinks and muscle activity is also disadvantageous, and the neural signals obtained are smudged as they pass through the cerebrospinal fluid, meninges, and skull. These limitations may be addressed with alternative neuroimaging methods independently&#8211; such as fMRI, NIRS &#8211; or by combining EEG with these alternate approaches. However, as previously mentioned, these approaches also carry their own limitations. The requisite contrast conditions and the lack of baseline and polarity in fMRI are notable examples. With respect to alternative brain imaging techniques, ERP recording has many advantages- most particularly its remarkable temporal resolution, which is at the level of milliseconds. It is also non-invasive and minimally uncomfortable for the participant, and is not associated with any significant risks or dangers. ERP recording is economically sound, especially when compared to other neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) 15. It offers a look into the neural events that occur in cognitive, sensory, and motor processes, and in the future, could be applied to explore preconscious processes.

While neuroimaging advances have undeniably augmented our understanding of the functions of the brain, these advances have a largely static emphasis on elucidating the structures of the brain. This subsequently leaves the dynamic temporal features of brain networks relatively shrouded in obscurity, as neuroimaging methods that do address these temporal aspects, such as fMRI and near-infrared spectroscopy (NIRS), produce temporal resolutions that are inadequate compared to that of EEG. It is thus pertinent to better understand and employ the use of ERP recording, which is able to produce vast amounts of meaningful information that otherwise would be unknown. ERP recording is a non-invasive analytical tool that allows cognitive neuroscientists to track the rapid temporal modulations of neural activity that are elicited by cognitive, sensory, and motor processes. It involves placing electrodes on the scalp to capture the electrical postsynaptic responses of large neuronal populations2 to specific events or stimuli. ERPs are electroencephalographic changes that are time-locked to sensory, motor, or cognitive events, and are believed to represent the summation of postsynaptic potentials produced during information processing3. These ERP waveforms are characterized by their latency, amplitude, polarity, and scalp distribution, providing a rich array of neurological data that may stimulate further insight into the neural connections that contribute to cognition.

The goal of ERP recording and electroencephalography (EEG) is to obtain information about the foundational neural processes involved in higher-order, complex cognitive operations4. ERPs are defined by their negative or positive fluctuation, as well as their location on the scalp and the time in which they appear after the onset of the stimulus. Various ERPs have been associated with different aspects of cognitive processing. For example, we have been looking at the N400 event-related brain potential5, a negative waveform that is elicited 400 ms after the onset of meaningful stimuli such as words6, and whose distribution on the scalp is known to depend on the semantic category of these stimuli. The N400 is an index of semantic activations, and studies have shown that it has a larger amplitude for words which activate more representations, such as concrete words (e.g., banana) that activate both visual and verbal representations, than for abstract words (e.g., idea), which activate only verbal representations7,8. Research also supports the idea that even mild symptoms of schizophrenia, as measured by schizotypy scales, are associated with abnormally excessive semantic activation of the N4009. As such, we are exploring whether antipsychotic medication, which decreases schizophrenic symptom presentation, normalizes abnormal semantic activations of the N400 in healthy individuals with high levels of schizotypy. Here, the use of ERPs in a semantic categorization paradigm is advantageous for studying the effects of antipsychotics on the N400.

As ERP recording is a non-invasive and relatively economical method to assess neural functioning, it can be applied in a wide range of domains, as evidenced by the substantial number of ERP studies in cognitive neuroscience, neurology, neuropsychology, psycholinguistics, and cognitive psychology. Its versatility enables investigators to ask pertinent research questions about the relative timing of neural events in a large variety of domains, including language, cognition, and the study of various psychiatric disorders10 such as schizophrenia, bipolar affective disorder, depression, and alcohol dependence disorder, and it offers substantial advantages over alternative methods of neuroimaging, such as functional magnetic resonance imaging (fMRI). Some of these include its excellent temporal resolution, which elucidates brain activity down to the millisecond. ERP recording also directly indexes excitatory post-synaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs) through which many brain computations are performed, something that fMRI does not do. Another advantage of ERP recording is that it offers the possibility of distinguishing inhibitory activity (neuronal hyperpolarizations) from excitatory activity (neuronal depolarization), whereas in fMRI, greater signals are not clearly differentiated between these two. Further, the ERP method does not require a contrast condition: raw ERPs can be examined for just one experimental condition, a distinction from fMRI where control conditions must be subtracted from the experimental condition, leading to uncertainty in associating observations with experimental or contrast conditions. ERP recordings&#8217; utility, relative cost-effectiveness and associated advantages offer strong rationale for the use of ERPs in cognitive neuroscience as a way to track rapid temporal changes in neural activity. Followed is a step-by-step guide to the basics of running an EEG experiment and recording event-related potentials.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>EEG acquisition software (Scan 4.5)</td>
			<td>Neuroscan</td>
			<td>http://www.neuroscan.com/scan.cfm</td>
			<td></td>
		</tr>
		<tr>
			<td>Digital EEG Amplifier (NuAmp)</td>
			<td>Neuro Scan Labs</td>
			<td><a href="http://www.neuroscan.com/documents/AF573-01%20CURRY%20NuAmpsExpressPRESSD4.pdf">http://www.neuroscan.com/documents/AF573-01%20CURRY%20NuAmpsExpressPRESSD4.pdf</a></td>
			<td></td>
		</tr>
		<tr>
			<td>2 computers</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Matlab</td>
			<td>The MathWorks, Inc</td>
			<td><a href="http://www.mathworks.com/products/matlab/">http://www.mathworks.com/products/matlab/</a></td>
			<td></td>
		</tr>
		<tr>
			<td>EEGLab Matlab toolbox</td>
			<td></td>
			<td>http://sccn.ucsd.edu/eeglab/</td>
			<td></td>
		</tr>
		<tr>
			<td>ERPLAB Toolbox</td>
			<td></td>
			<td><a href="http://erpinfo.org/erplab">http://erpinfo.org/erplab</a></td>
			<td></td>
		</tr>
		<tr>
			<td>Stimulus generation software</td>
			<td>E-Prime</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>ECI Electrode cap</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/caps/</td>
			<td></td>
		</tr>
		<tr>
			<td>Special Head Measuring Tape (4 Colour ribbon)</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/supplies/</td>
			<td></td>
		</tr>
		<tr>
			<td>Disposable Sponge Disks</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/supplies/</td>
			<td></td>
		</tr>
		<tr>
			<td>EEG Abrasive Skin Prepping Gel (Nuprep)</td>
			<td>Weaver and Company</td>
			<td>http://www.weaverandcompany.com/nuprep.html</td>
			<td></td>
		</tr>
		<tr>
			<td>Body harness</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/supplies/</td>
			<td></td>
		</tr>
		<tr>
			<td>Cap straps</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/supplies/</td>
			<td></td>
		</tr>
		<tr>
			<td>Electro-gel</td>
			<td>Electro-cap International, Inc</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Blunt needle (BD Vacutainer PrecisionGlide Multiple Sample Needle)</td>
			<td>Becton, Dickinson and Company</td>
			<td>367211; see http://www.bd.com/resource.aspx?IDX=7559</td>
			<td></td>
		</tr>
		<tr>
			<td>Syringe</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/supplies/</td>
			<td></td>
		</tr>
		<tr>
			<td>2 Ear Electrodes</td>
			<td>Electro-cap International, Inc</td>
			<td>http://www.electro-cap.com/index.cfm/supplies/</td>
			<td></td>
		</tr>
		<tr>
			<td>Alcohol wipes</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Red pencil</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton swabs</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Facilities and supplies for participants to wash their hair after the experiment- sink, shampoo, comb, towels, hair dryer</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

investigating the effects of antipsychotics and schizotypy on the n400 using event-related potentials and semantic categorization

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in part because of its excellent spatial resolution, which allows researchers to identify brain areas associated with specific cognitive processes. However, in the quest to localize brain functions, it is relevant to note that many cognitive, sensory, and motor processes have temporal distinctions that are imperative to capture, an aspect that is left unfulfilled by fMRI&#8217;s suboptimal temporal resolution. To better understand cognitive processes, it is thus advantageous to utilize event-related potential (ERP) recording as a method of gathering information about the brain. Some of its advantages include its fantastic temporal resolution, which gives researchers the ability to follow the activity of the brain down to the millisecond. It also directly indexes both excitatory and inhibitory post-synaptic potentials by which most brain computations are performed. This sits in contrast to fMRI, which captures an index of metabolic activity. Further, the non-invasive ERP method does not require a contrast condition: raw ERPs can be examined for just one experimental condition, a distinction from fMRI where control conditions must be subtracted from the experimental condition, leading to uncertainty in associating observations with experimental or contrast conditions. While it is limited by its poor spatial and subcortical activity resolution, ERP recordings&#8217; utility, relative cost-effectiveness, and associated advantages offer strong rationale for its use in cognitive neuroscience to track rapid temporal changes in neural activity. In an effort to foster increase in its use as a research imaging method, and to ensure proper and accurate data collection, the present article will outline &#8211; in the framework of a paradigm using semantic categorization to examine the effects of antipsychotics and schizotypy on the N400 &#8211; the procedure and key aspects associated with ERP data acquisition.

Five figures have been included to aid researchers in obtaining optimal ERP recording. Figure 1 depicts ERP waveforms obtained following successful completion of this protocol; it constitutes a &#8220;good&#8221; result due to its accurate recording. Figure 2 on the other hand, illustrates ERP waveforms that would characterize a poor execution of the protocol, resulting in &#8220;bad&#8221; results, which are most notably identified in excessively noisy signals. Figure 3 shows the common problems that may arise in ERP recording that can impede proper data collection. High activity can be interpreted in the high frequency and large amplitudes in the waves. In contrast, a &#8220;flatline&#8221; indicates a lack of activity or improper connectivity. Figures 4 and 5 show the grand averages for the main results of our investigation into the effects of antipsychotics and schizotypy on the N400, as measured using a semantic categorization paradigm.
<img alt="Figure 1" src="/files/ftp_upload/52082/52082fig1highres.jpg" /> 
Figure 1.&#160;Good Result. This figure depicts the averaged ERP waveforms of one subject over all trials following successful execution of the technique, resulting in no flat lines or excessive noise. Note that the waves will look slightly different depending on the experimental paradigm used- tasks that rely heavily on different processes (cognitive, sensory, and motor) will produce different waveforms depending on the content of the task and the skills required by the task. <a href="https://www.jove.com/files/ftp_upload/52082/52082fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" src="/files/ftp_upload/52082/52082fig2highres.jpg" /> 
Figure 2.&#160;Poor Result. This figure depicts the averaged ERP waveforms of one subject over all trials following inadequate execution of the technique. The waveforms shown here are poor due to the noise, as well as the flat line in FP2. Note also the lack of recognizable ERP components in the EEG. <a href="https://www.jove.com/files/ftp_upload/52082/52082fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" src="/files/ftp_upload/52082/52082fig3highres.jpg" /> 
Figure 3. Common Problems. This figure depicts the common problems that arise with this technique; namely, eye movement, muscle movement, or saturation. Note that these problems can occur in any of the channels, so be sure to check all of them. <a href="https://www.jove.com/files/ftp_upload/52082/52082fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" src="/files/ftp_upload/52082/52082fig4highres.jpg" /> 
Figure 4. Effect of Schizotypy. This figure depicts the grand average ERPs in the placebo condition. Red lines correspond to participants with high scores on the schizotypal personality questionnaire. Black lines correspond to participants with low schizotypy as determined by the questionnaire.
<img alt="Figure 5" src="/files/ftp_upload/52082/52082fig5highres.jpg" /> 
Figure 5. Effects of medication in high schizotypy individuals. This figure depicts the grand average ERPs, where red corresponds to medication (Olanzapine), and black corresponds to placebo. <a href="https://www.jove.com/files/ftp_upload/52082/EEGLab_Tutorial.mp4" target="_blank">Please click here to view a larger version of this figure.</a>
Animated Figure 1. This figure can be used as a guide for processing the data and obtaining ERPs.

Watch this Scientific Journal Video about Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization at JoVE.com

Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization

Using event-related EEG potentials (ERPs), we investigate the effects of antipsychotic medications on abnormal semantic brain activations in healthy individuals with schizotypal traits. We use ERPs to track distinct changes in brain activity, shedding insight into the cognitive processes associated with semantic categorization.

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in ...

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Research

JoVE Journal

Behavior

Measuring Neural and Behavioral Activity During Ongoing Computerized Social Interactions: An Examination of Event-Related Brain Potentials

Social exclusion is a complex social phenomenon with powerful negative consequences. Given the impact of social exclusion on mental and emotional health, an understanding of how perceptions of social exclusion develop over the course of a social interaction is important for advancing treatments aimed at lessening the harmful costs of being excluded. To date, most scientific examinations of social exclusion have looked at exclusion after a social interaction has been completed. While this has been very helpful in developing an understanding of what happens to a person following exclusion, it has not helped to clarify the moment-to-moment dynamics of the process of social exclusion. Accordingly, the current protocol was developed to obtain an improved understanding of social exclusion by examining the patterns of event-related brain activation that are present during social interactions. This protocol allows greater precision and sensitivity in detailing the social processes that lead people to feel as though they have been excluded from a social interaction. Importantly, the current protocol can be adapted to include research projects that vary the nature of exclusionary social interactions by altering how frequently participants are included, how long the periods of exclusion will last in each interaction, and when exclusion will take place during the social interactions. Further, the current protocol can be used to examine variables and constructs beyond those related to social exclusion. This capability to address a variety of applications across psychology by obtaining both neural and behavioral data during ongoing social interactions suggests the present protocol could be at the core of a developing area of scientific inquiry related to social interactions.

Research on social exclusion has grown tremendously in recent years. As the field expands, it is imperative to develop sophisticated methodologies allowing for the simultaneous measurement of neural and behavioral outcomes during social exclusion. This protocol utilizes event-related brain potentials to record ongoing neural activity during computerized social interactions.

Social exclusion is a complex social phenomenon with powerful negative consequences. Given the impact of social exclusion on mental and emotional health, ...

Infant Auditory Processing and Event-related Brain Oscillations

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral and temporal changes that are characteristic of human language. These abilities lay the foundation for effective language acquisition; allowing infants to hone in on the sounds of their native language. Invasive procedures in animals and scalp-recorded potentials from human adults suggest that simultaneous, rhythmic activity (oscillations) between and within brain regions are fundamental to sensory development; determining the resolution with which incoming stimuli are parsed. At this time, little is known about oscillatory dynamics in human infant development. However, animal neurophysiology and adult EEG data provide the basis for a strong hypothesis that rapid auditory processing in infants is mediated by oscillatory synchrony in discrete frequency bands. In order to investigate this, 128-channel, high-density EEG responses of 4-month old infants to frequency change in tone pairs, presented in two rate conditions (Rapid: 70 msec ISI and Control: 300 msec ISI) were examined. To determine the frequency band and magnitude of activity, auditory evoked response averages were first co-registered with age-appropriate brain templates. Next, the principal components of the response were identified and localized using a two-dipole model of brain activity. Single-trial analysis of oscillatory power showed a robust index of frequency change processing in bursts of Theta band (3 - 8 Hz) activity in both right and left auditory cortices, with left activation more prominent in the Rapid condition. These methods have produced data that are not only some of the first reported evoked oscillations analyses in infants, but are also, importantly, the product of a well-established method of recording and analyzing clean, meticulously collected, infant EEG and ERPs. In this article, we describe our method for infant EEG net application, recording, dynamic brain response analysis, and representative results.

High-density electroencephalography (dEEG) is being used increasingly to study brain development and plasticity in the early years of life. Here we present an application of sophisticated analysis techniques that builds on traditional EEG recording to understand the oscillatory dynamics of rapid auditory processing in the infant brain.

Rapid auditory processing and acoustic change detection abilities play a critical role in allowing human infants to efficiently process the fine spectral ...

Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown gene expression in a relatively focused region without significant damage to the brain tissue. After recovery, the injected mouse can be tested on various behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice by measuring the amount of time that a mouse spends in the center of a novel open field. A more anxious mouse will spend significantly less time in the center of the novel field compared to controls. The FST assesses the anti-depressive phenotype by quantifying the amount of time that mice spend immobile when placed into a bucket of water. A mouse with an anti-depressive phenotype will spend significantly less time immobile compared to control animals. The goal of this protocol is to use the stereotactic injection of a lentivirus in conjunction with behavioral tests to assess how genetic factors modulate animal behaviors.

Stereotactic injection of lentiviruses expressing cDNAs or shRNAs can modulate gene expression in specific brain areas of mice. Here, we present a protocol to combine stereotactic injections with behavioral tasks, such as the Open Field Test (OFT) and the Forced Swim Test (FST).

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or ...

Event-related Potentials During Target-response Tasks to Study Cognitive Processes of Upper Limb Use in Children with Unilateral Cerebral Palsy

Unilateral Cerebral Palsy (CP) is a neurodevelopmental disorder that is a very common cause of disability in childhood. It is characterized by unilateral motor impairments that are frequently dominated in the upper limb. In addition to a reduced movement capacity of the affected upper limb, several children with unilateral CP show a reduced awareness of the remaining movement capacity of that limb. This phenomenon of disregarding the preserved capacity of the affected upper limb is regularly referred to as Developmental Disregard (DD). Different theories have been postulated to explain DD, each suggesting slightly different guidelines for therapy. Still, cognitive processes that might additionally contribute to DD in children with unilateral CP have never been directly studied. The current protocol was developed to study cognitive aspects involved in upper limb control in children with unilateral CP with and without DD. This was done by recording event-related potentials (ERPs) extracted from the ongoing EEG during target-response tasks asking for a hand-movement response. ERPs consist of several components, each of them associated with a well-defined cognitive process (e.g., the N1 with early attention processes, the N2 with cognitive control and the P3 with cognitive load and mental effort). Due to its excellent temporal resolution, the ERP technique enables to study several covert cognitive processes preceding overt motor responses and thus allows insight into the cognitive processes that might contribute to the phenomenon of DD. Using this protocol adds a new level of explanation to existing behavioral studies and opens new avenues to the broader implementation of research on cognitive aspects of developmental movement restrictions in children.

Several children with unilateral Cerebral Palsy seem to disregard the preserved capacity of their affected upper limb. This Developmental Disregard is extensively described in the literature but the involved cognitive processes have not been studied. To study underlying cognitive factors of upper limb control, an event-related potential protocol was developed.

Unilateral Cerebral Palsy (CP) is a neurodevelopmental disorder that is a very common cause of disability in childhood. It is characterized by unilateral ...

A Within-subjects Experimental Protocol to Assess the Effects of Social Input on Infant EEG

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants socially interact. Electroencephalography (EEG) power is an advantageous technique to assess infant functional neural activation. However, many studies record infant EEG only during one baseline condition. This protocol describes a paradigm that is designed to comprehensively assess infant EEG activity in both social and nonsocial contexts as well as tease apart how different types of social inputs differentially relate to infant EEG. The within-subjects paradigm includes four controlled conditions. In the nonsocial condition, infants view objects on computer screens. The joint attention condition involves an experimenter directing the infant's attention to pictures. The joint attention condition includes three types of social input: language, face-to-face interaction, and the presence of joint attention. Differences in infant EEG between the nonsocial and joint attention conditions could be due to any of these three types of input. Therefore, two additional conditions (one with language input while the experimenter is hidden behind a screen and one with face-to-face interaction) were included to assess the driving contextual factors in patterns of infant neural activation. Representative results demonstrate that infant EEG power varied by condition, both overall and differentially by brain region, supporting the functional nature of infant EEG power. This technique is advantageous in that it includes conditions that are clearly social or nonsocial and allows for examination of how specific types of social input relate to EEG power. This paradigm can be used to assess how individual differences in age, affect, socioeconomic status, and parent-infant interaction quality relate to the development of the social brain. Based on the demonstrated functional nature of infant EEG power, future studies should consider the role of EEG recording context and design conditions that are clearly social or nonsocial.

This novel protocol is designed to assess the neural bases of social interaction in infants. The paradigm is designed to tease apart how various social inputs such as language, joint attention, and face-to-face interaction relate to infant neural activation. Infant EEG power is recorded during both social and nonsocial conditions.

Despite the importance of social interactions for infant brain development, little research has assessed functional neural activation while infants ...

Using Gold-standard Gait Analysis Methods to Assess Experience Effects on Lower-limb Mechanics During Moderate High-heeled Jogging and Running

A limited number of studies have explored lower-limb biomechanics during high-heeled jogging and running, and most studies have failed to clarify the wearing experience of subjects. This protocol describes the differences in lower-limb kinematics and ground reaction force (GRF) between experienced wearers (EW) and inexperienced wearers (IEW) during moderate high-heeled jogging and running. A three-dimensional (3D) motion analysis system with a configured force platform was used to synchronously capture lower-limb joint movements and GRF. 36 young females volunteered to participate in this study and were asked about high-heeled shoe-wearing experience, including frequency, duration, heel types, and heel heights. Eleven who had the experience of 3 to 6 cm heels for a minimum of three days per week (6 h per day) for at least two years and eleven who wore high heels less than twice per month participated. Subjects performed jogging and running at comfortable low and high speeds, respectively, with the right foot completely stepping onto a force platform when passing by along a 10 m walkway. EW and IEW adopted different biomechanical adaptations while jogging and running. IEW exhibited a generally larger range of joint movement, while EW showed a dramatically larger loading rate of GRF during running. Hence, further studies on the lower-limb biomechanics of high-heeled gait should strictly control the wearing experience of the subjects.

This study investigated lower-limb kinematics and ground reaction force (GRF) during moderate high-heeled jogging and running. Subjects were divided into groups of experienced wearers and inexperienced wearers. A three-dimensional motion analysis system with a configured force platform captured lower-limb joint movements and GRF.

A limited number of studies have explored lower-limb biomechanics during high-heeled jogging and running, and most studies have failed to clarify the ...

A Semantic Priming Event-related Potential (ERP) Task to Study Lexico-semantic and Visuo-semantic Processing in Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) have characteristic deficits in understanding the meaning of language, or semantic processing. However, some evidence indicates that semantic processing of non-linguistic stimuli is intact, suggesting that semantic deficits may be language-specific. To appropriately characterize semantic processing deficits in individuals with ASD, comparison of within-modality linguistic (e.g., written words) and non-linguistic (e.g., pictures) stimuli is required. This paper describes such a methodology that makes use of a semantic priming paradigm during concurrent recording of electroencephalographic (EEG) data. EEG provides a dynamic measure of brain activity that is well-suited to characterize subtle differences in semantic processing that may not be observable at the behavioral level. The semantic priming paradigm presents a prime picture or word (e.g., dog) followed by a target picture or word that is either related (e.g., cat) or unrelated (e.g., pencil) to the prime. This paradigm can thus be used to evaluate semantic processing across different modalities, and to compare lexico-semantic and visuo-semantic processing abilities in individuals with ASD and how they might differ from TD individuals. The specific steps involved in creating the stimuli, performing the EEG testing, and analyzing the EEG data are discussed. Representative results illustrate how the N400 component of the event-related potential (ERP) is reduced following semantically-related prime-target pairs compared to unrelated pairs. Comparisons of the N400 between conditions, modalities, and groups can provide estimates of the success of semantic processing, and can thereby be used to characterize semantic deficits in individuals with ASD or other clinical populations.

A Semantic Priming Event-related Potential ERP Task to Study Lexico-semantic and Visuo-semantic Processing in Autism Spectrum Disorder

This paper describes a semantic priming ERP task using within-modality pairs of pictures and words to investigate semantic processing in individuals with autism spectrum disorder (ASD).

Individuals with autism spectrum disorder (ASD) have characteristic deficits in understanding the meaning of language, or semantic processing. However, ...

Using a Classroom-Based Deese Roediger McDermott Paradigm to Assess the Effects of Imagery on False Memories

Associated word list procedures can elicit false memories in predictable ways by inducing associative processing, thus making it harder to monitor the accuracy of memories. The purpose of the method presented here was to induce false memories using lists of either semantically or phonologically related words and to assess the effects of imagery instructions on the recall and recognition of those false memories. To do this, we used a modified version of the Deese Roediger McDermott (DRM) paradigm. We adapted word lists from previous DRM studies to suit imagery procedures and created an automated presentation to present the word lists in classroom settings. We then recruited undergraduate classes and instructed some of the classes to create mental images of the list words as they were being presented, while instructing the other classes to simply remember the words. The automated presentation presented word lists to participants, one word at a time, alternating between phonologically and semantically related lists. Participants used paper-pencil recall packets to immediately recall list items, complete a distractor activity, and take a subsequent final recognition test. Often, participants immediately recalled and later recognized words that were related to the list items but were not actually presented; these are known as critical lures and indicate a false memory. The protocol detailed here describes a four-step procedure - list presentation, immediate recall, distractor phase, and final recognition - that can assess the effects of list type and imagery instruction within the DRM paradigm on memory. The automated nature of the list presentation provides the ability to systematically vary variables of interest, and the paper and pencil method of data collection affords an easily accessible method for collecting data in classroom settings. The protocol also offers options to modify the procedure to a more traditional DRM paradigm without imagery and/or list type manipulations. The use of this protocol can provide results relevant to both classroom learning and cognitive science principles.

The method presented here induced false memories using lists of related words and also assessed the effects of imagery instructions on the recall and recognition of those false memories. This protocol details a modified version of the Deese Roediger McDermott (DRM) paradigm.

Associated word list procedures can elicit false memories in predictable ways by inducing associative processing, thus making it harder to monitor the ...

Defining the Role Of Language in Infants' Object Categorization with Eye-tracking Paradigms

Assessing infant category learning is a challenging but vital aspect of studying infant cognition. By employing a familiarization-test paradigm, we straightforwardly measure infants&#8217; success in learning a novel category while relying only on their looking behavior. Moreover, the paradigm can directly measure the impact of different auditory signals on the infant categorization across a range of ages. For instance, we assessed how 2-year-olds learn categories in a variety of labeling environments: in our task, 2-year-olds successfully learned categories when all exemplars were labeled&#160;or the first two exemplars were labeled, but they failed to categorize when no exemplars were labeled or only the final two exemplars were labeled. To determine infants&#8217; success in such tasks, researchers can examine both the overall preference displayed by infants in each condition and infants&#8217; pattern of looking over the course of the test phase, using an eye-tracker to provide fine-grained time-course data. Thus, we present a powerful paradigm for identifying the role of language, or any auditory signal, in infants&#8217; object category learning.

Here we present a protocol for familiarization-test paradigms which provide a direct test of infant categorization and help to define the role of language in early category learning.

Assessing infant category learning is a challenging but vital aspect of studying infant cognition. By employing a familiarization-test paradigm, we ...

Dissociation of the Confounding Influences of Expectancy and Integrative Difficulty Residing in Anomalous Sentences in Event-related Potential Studies

The confounding factors of unexpectedness and semantic integration difficulty naturally residing in anomalous sentences in language studies make it difficult to determine the underlying processing mechanism of ERP components. Unlike the traditional static approach of manipulating expectancy through corpus frequency or cloze probability, this protocol proposes a dynamic method to enhance participants&#39; expectancy for rarely-met anomalous sentences by multiple repetitions while maintaining their semantic integration difficulties. To address the time cost increase resulting from multiple repetitions, this protocol proposes to repeat only the strictly simplified core structure extracted from the anomalous sentence before presenting the semantically enriched, much more informative complete anomalous sentence containing the anomalous core structure to reinitiate the semantic integration processing. The complete anomalous sentence elicited a P600 effect. It suggests that the participants did not give up processing the anomalous information after repetitions and the same semantic integration difficulty was successfully reinitiated. Importantly, the representative experimental results reveal that the greatly attenuated N400 effect caused by multiple repetitions was not recovered by the follow-up reinitiated semantic integration difficulty. It suggests that the attenuated N400 effect should be mainly attributed to the enhancement of expectancy for anomalous information by multiple repetitions. The experimental results show that this method can effectively enhance participants&#39; expectancy for anomalous sentences while retaining the semantic integration difficulty.

We present a protocol to dissociate the intertwining factors of integrative difficulty and unexpectedness in semantically anomalous sentences by applying multiple repetitions to enhance participant&#39;s expectancy for anomalous sentences. The dissociation helps to investigate the major contributor of elicited event-related potentials (ERP) effects such as N400 in language studies.

The confounding factors of unexpectedness and semantic integration difficulty naturally residing in anomalous sentences in language studies make it ...