This work was supported by EFRI-MC3: # 1137237 awarded to S.V.S. and J.T.G.

All tasks were performed according to an approved protocol submitted to the Institutional Review Board (IRB) of the Cleveland Clinic Foundation. An informed consent process was conducted with each patient prior to all research activities. In this example, a subject that meets study criterion that has had stereo-electroencephalography (SEEG) electrodes implanted for seizure is chosen. The project was discussed with the subject and they have consented to participate.
1. Patient Enrollment
<ol>
	<li>Evaluate patients with refractory epilepsy in consideration for intracranial electrode implantation. If the patient is a good candidate for the invasive surgery, analyze the patient&#8217;s MRI, PET and MEG along with the seizure pathology in order to optimize placement of the electrodes. A clinical team carries out all evaluations and no decisions are made for research purposes. .</li>
	<li>Identify eligible patients for the study subsequent to evaluation for implantation and verify the patients per the approved IRB protocol based on the inclusion/exclusion criteria. 
	NOTE: It is in the best interest of the patient to include subjects with an aura in the inclusion criteria. Patients with auras are able to notify the researchers that they are about to have a seizure; giving the researchers and patient time to take the necessary precautions (pressing the seizure alarm to notify the clinical staff and pulling all equipment out of the way). However, if subjects are recruited that do not have an aura, ensure that the patient input devices can be readily removed from the patient area and that the staff is aware of the research equipment and protocol.</li>
	<li>Obtain informed consent prior to any research activities in accordance with the IRB. During the informed consent, explain the research, emphasizing that participation is strictly voluntary and will in no way impact the patients clinical care. In most cases there is no direct benefit to the patient and their willingness to participate is altruistic.</li>
	<li>Maintain respect for the patient&#8217;s rights and privacy at all times. Remind the patients that their information will remain anonymous and confidential and they may cease participation in the study at any time under no consequence.</li>
	<li>Have the patient sign and date the informed consent if he or she understands and agrees to participate in the study. Leave one copy is left with the patient to review; should they have any questions or concerns encourage the patients to contact the PI.</li>
</ol>
2. Behavior System Set-up
<ol>
	<li>Before bringing the equipment into the room, ensure that there is sufficient space in the patient&#8217;s room, as well as access to the necessary outlets (2).</li>
	<li>Check that all equipment and wires are ready to expedite the set up. The behavioral system includes an FDA approved robotic arm (which allows the subject to control a cursor during the task), a laptop computer to control the behavioral program, a monitor for presenting the task stimuli, and a data acquisition system to store the electrophysiological and behavioral data. 
	NOTE: Make necessary modifications to meet specific needs of one&#8217;s research. For instance, use a button box for the patient interface instead of the robotic arm.</li>
	<li>If the patient is not presently positioned in a manner suitable to complete the task, assist the patient to a reclining chair (or bed) with arms, should they have a seizure. 
	NOTE: It is a good idea to discuss the study design, equipment, etc. with all the members of the monitoring unit to inform them of what is going on, how the group will be interacting with the patients, and any possible issues that may arise.</li>
	<li>When the patient is ready, bring the behavioral system into the room and begin booting up the behavioral system and robotic arm.</li>
	<li>Connect the digital event marker output from the behavioral computer to the DC channels of the electrophysiological acquisition system in order to time lock the recorded SEEG signals with behavioral event markers. 
	NOTE: At this center there is a separate electrophysiological acquisition system designated for research purposes, which does not interfere with the clinical acquisition system. However, it is possible to use the clinical acquisition system by working with the appropriate personnel. All efforts should be made not to disrupt the clinical acquisition.</li>
	<li>Calibrate the robotic arm and position it such that the range of motion is comfortable for the patient. If using another interface device, ensure that the equipment is operating correctly and is positioned comfortably for the subject to use.</li>
	<li>While using the robotic arm, ensure that the emergency stop buttons are easily accessible by the researchers throughout the behavioral task. In the event of a seizure, the emergency stop button is pressed and the equipment is pulled away from the patient so that they do not harm themselves. In addition, we do not use the velcro straps that come with the robot system to facilitate removal from the patient in case a seizure occurs. 
	NOTE: In this example, the parallel port of the behavior rig is connected to the digital input port of the acquisition system using a parallel port cable. Additional analog signals such as the x &#38; y position of the robotic arm are recorded simultaneously.</li>
</ol>
3. Behavioral Task
<ol>
	<li>Explain the task to the patient following the completion of the rig set up and calibration of the interface device.</li>
	<li>Use a behavioral task similar to the children&#8217;s card game of &#8220;war&#8221;. Ask the patient to make wagers as to whether their card is greater than the computer&#8217;s card. The choice of the wager is based on the patients&#8217; perception of the relative value of their card. Simplify the task for subsequent analysis, by only using cards of one suit and limiting the deck to the 2, 4, 6, 8, and 10 numbered cards.</li>
	<li>Show a fixation cue on the screen for 350 msec. Ensure the patient holds the cursor over the fixation mark to initiate the task.</li>
	<li>Show the stimulus for 1,000 msec. Allow the patient to see their card with the computer&#8217;s card next to it face down.</li>
	<li>Following the cards disappearance, show a go-cue (&#60;5,000 msec) displaying two options, asking the patient to bet either $5 or $20, based on their card. Ask the patient to place the bet by moving the cursor using the robotic arm, over their chosen wager. Randomize the wager position from trial to trial to ensure no bias based on position.</li>
	<li>After the wager has been selected, notice a 250 - 500 msec delay (blank screen), followed by the revelation of the computer&#8217;s card (1,000 - 1,250 msec). Observe the outcome (1,000 msec), whether the trial was a win, lose, or draw and how much was won or lost.</li>
	<li>Allow the patient to practice until they are confident in their performance and have no questions.</li>
</ol>
4. Data Acquisition
<ol>
	<li>Record the data when the patient is ready and verify that the settings on the research (or clinical) acquisition system are appropriately selected.</li>
	<li>Turn off the room lights and TV to keep the background noise to a minimum during the recording. Additionally, ask the patient to refrain from behaviors such as tapping their foot, talking or shaking their legs.</li>
	<li>Begin the task and record the patient performing the task. Ask the subject to perform the task for 30 min. The sampling rate of the robotic arm system is 1 KHz, and that of SEEG recording system is 2 KHz. 
	NOTE: This duration may be different for other paradigms.</li>
</ol>
5. Data Analysis
<ol>
	<li>First, de-identify the recorded SEEG data to ensure that the patient&#8217;s information remains confidential and that his/her data is submitted anonymously.</li>
	<li>Obtain the coordinates of the electrode locations from the postoperative CT and preoperative MRI.</li>
	<li>Align the neurophysiological recordings with the digital timestamps of interests from the behavioral task.</li>
	<li>Apply signal analysis methods to analyze the event dependent brain activity modulation. 
	NOTE: In this study, power spectral density (PSD) of the event related SEEG signals was calculated using Chronux multitaper toolbox26,27. Each trial data was aligned with respect to the relevant event (time zero), and the calculated PSD was normalized in each frequency bin with respect to the baseline PSD.</li>
</ol>

<ol>
	<li>Rosenow, F., Luders, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Presurgical+evaluation+of+epilepsy.">Presurgical evaluation of epilepsy.</a> Brain. 124, 1683-1700 (1093).</li><li>Adelson, P. D., 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=Use+of+subdural+grids+and+strip+electrodes+to+identify+a+seizure+focus+in+children.">Use of subdural grids and strip electrodes to identify a seizure focus in children.</a> Pediatr. Neurosurg. 22 (4), 174-180 (1995).</li><li>Jayakar, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Invasive+EEG+monitoring+in+children:+When,+where,+and+what.">Invasive EEG monitoring in children: When, where, and what.</a> J Clin Neurophysiol. 16, 408-418 (1999).</li><li>Almeida, A. N., Martinez, V., Feindel, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+first+case+of+invasive+EEG+monitoring+for+the+surgical+treatment+of+epilepsy:+Historical+significance+and+context.">The first case of invasive EEG monitoring for the surgical treatment of epilepsy: Historical significance and context.</a> Epilepsia. 46, 1082-1085 (2005).</li><li>Dinner, D. S., Luders, H. O., Klem, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+electrocorticography:+Cleveland+clinic+experience.">Chronic electrocorticography: Cleveland clinic experience.</a> Electroencephalogr Clin Neurophysiol. , 58-69 (1998).</li><li>Bancaud, J., 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=Functional+Stereotaxic+Exploration+(Seeg)+of+Epilepsy.">Functional Stereotaxic Exploration (Seeg) of Epilepsy.</a> Electroencephalogr Clin Neurophysiol. 28, 85 (1970).</li><li>Chassoux, F., 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=Intralesional+recordings+and+epileptogenic+zone+in+focal+polymicrogyria.">Intralesional recordings and epileptogenic zone in focal polymicrogyria.</a> Epilepsia. 49, 51-64 (2008).</li><li>Lo Russo, G., 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=Focal+cortical+resection+in+malformations+of+cortical+development.">Focal cortical resection in malformations of cortical development.</a> Epileptic Disord. 5, S115-S123 (2003).</li><li>Avanzini, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Discussion+of+stereoelectroencephalography.">Discussion of stereoelectroencephalography.</a> Acta neurologica Scandinavica Supplementum. , 152-170 (1994).</li><li>Cossu, 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=Stereo-EEG+in+children.">Stereo-EEG in children.</a> Child Nerv Syst. 22, 766-778 (2006).</li><li>Cossu, 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=Epilepsy+surgery+in+children:+Results+and+predictors+of+outcome+on+seizures.">Epilepsy surgery in children: Results and predictors of outcome on seizures.</a> Epilepsia. 49, 65-72 (2008).</li><li>Cossu, 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=Stereoelectroencephalography+in+the+presurgical+evaluation+of+focal+epilepsy+in+infancy+and+early+childhood+Clinical+article.">Stereoelectroencephalography in the presurgical evaluation of focal epilepsy in infancy and early childhood Clinical article.</a> J Neurosurg-Pediatr. 9, 290-300 (2012).</li><li>Gonzalez-Martinez, J., 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=Stereoelectroencephalography+in+the+&amp;#34;difficult+to+localize&amp;#34;+refractory+focal+epilepsy:+early+experience+from+a+North+American+epilepsy+center.">Stereoelectroencephalography in the &amp;#34;difficult to localize&amp;#34; refractory focal epilepsy: early experience from a North American epilepsy center.</a> Epilepsia. 54, 323-330 (2013).</li><li>Vadera, S., 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=Stereoelectroencephalography+following+subdural+grid+placement+for+difficult+to+localize+epilepsy.">Stereoelectroencephalography following subdural grid placement for difficult to localize epilepsy.</a> Neurosurgery. 72, 723-729 (2013).</li><li>Hill, N. 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P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+short-term+memory+and+related+amygdala+recordings+in+patients+with+temporal+lobe+epilepsy.">Olfactory short-term memory and related amygdala recordings in patients with temporal lobe epilepsy.</a> Brain. 126, 1851-1863 (2003).</li><li>Rektor, I., Bares, M., Kubova, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Movement-related+potentials+in+the+basal+ganglia:+a+SEEG+readiness+potential+study.">Movement-related potentials in the basal ganglia: a SEEG readiness potential study.</a> Clin Neurophysiol. 112, 2146-2153 (2001).</li><li>Rektor, I., Louvel, J., Lamarche, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracerebral+recording+of+potentials+accompanying+simple+limb+movements:+a+SEEG+study+in+epileptic+patients.">Intracerebral recording of potentials accompanying simple limb movements: a SEEG study in epileptic patients.</a> Electroencephalogr Clin Neurophysiol. 107, 277-286 (1998).</li><li>Mitra, P., Bokil, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Observed Brain Dynamics. , (2008).</li><li>Lachaux, J. 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D., 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=Choosing+between+small,+likely+rewards+and+large,+unlikely+rewards+activates+inferior+and+orbital+prefrontal+cortex.">Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.</a> The Journal of neuroscience : the official journal of the Society for Neuroscience. 19, 9029-9038 (1999).</li><li>Lachaux, J. -. P., Axmacher, N., Mormann, F., Halgren, E., Crone, N. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High-frequency+neural+activity+and+human+cognition:+Past,+present+and+possible+future+of+intracranial+EEG+research.">High-frequency neural activity and human cognition: Past, present and possible future of intracranial EEG research.</a> Prog. 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The authors have no conflicts to disclose.

Here we have presented a method for performing intracranial electrophysiological studies in humans as they engage in a behavioral task. This methodology and its simple permutations are important for studying human movement and cognition. While there inherently exists advantages and disadvantages to any technique, recording from intracranial electrodes has advantages over other electrophysiological and imaging techniques. Two of the major advantages are the ability to collect high quality data with better control and desi...

Epilepsy is one of the most common brain disorders, characterized by chronically recurrent seizures resulting from excessive electrical discharges from groups of neurons. Epilepsy affects about 50 million people worldwide and approximately 40% of all individuals with epilepsy have intractable seizures that cannot completely be controlled by medical therapy1. Surgery may result in seizure free status if the brain areas responsible for the generation of seizures (the epileptogenic zone - EZ) are localized and surgically removed or disconnected. In order to define the anatomical location of the EZ and its proximity with possible cortical and subcortical eloquent areas, an array of non-invasive tools are available: analysis of seizure semiology, video-scalp electroencephalographic recordings (ictal and interictal recordings), neuropsychological testing, magnetoencephalography (MEG) and MRI2. When the noninvasive data is insufficient to precisely define the location of the hypothetical EZ, when there is the suspicion of early involvement of eloquent cortical and subcortical areas or when there is the possibility for multi-focal seizures, chronic invasive monitoring may be required3,4.
Methods of chronic invasive monitoring for defining the location and boundaries of an EZ may include subdural grids and strips, with electrodes placed on the brain&#8217;s surface, and stereo-electroencephalography (SEEG), when multiple depth electrodes are placed in the brain in a three-dimensional fashion. Subdural intracranial recordings were initially reported in 1939 when Penfield and colleagues used epidural single contact electrodes in a patient with an old left temporal-parietal fracture and whose pneumoencephalography disclosed diffuse cerebral atrophy5 . Subsequently, the use of subdural grid arrays became more popular after multiple publications during the 1980&#39;s demonstrated their safety and efficacy6. The SEEG method was developed and popularized in France by Jean Tailarach and Jean Bancaud during the 50&#8217;s and has been mostly used in France and Italy as the method of choice for invasive mapping in refractory focal epilepsy7-9.
The principle of SEEG is based on anatomo-electro-clinical correlations, which takes as its main principle the 3-dimensional spatial-temporal organization of the epileptic discharge within the brain in correlation with seizure semiology. The implantation strategy is individualized, with electrode placement based on a preimplantation hypothesis that takes into consideration the primary organization of the epileptiform activity and the hypothetical epileptic network involved in the propagation of seizures. According to several European and recent North American reports, SEEG methodology enables precise recordings from deep cortical and subcortical structures, multiple noncontiguous lobes, and bilateral explorations while avoiding the need for large craniotomies10-15. Afterwards, postoperative images are taken to obtain the exact anatomical position of the implanted electrodes. Subsequently, a monitoring period starts in which patients remain in the hospital for a period of 1 to 4 weeks in order to record interictal and ictal activities from the implanted electrodes. This monitoring period is an opportune time for studying brain function using event-related SEEG analysis, as there is no added risk and the patient typically views the research study as a welcome reprieve from the mundane monitoring period. The recordings garnered from intracranial electrodes are not only vital to improved evaluation and care of epilepsy patients, but additionally provide the exceptional opportunity to study human brain activity during behavioral paradigms.
Several researchers have already realized the opportunity to study invasive recordings from epilepsy patients. Hill et al. reported on the methodology for recording electrocorticographic (ECoG) signals from patients for functional cortical mapping16. ECoG recordings have also provided insight to motor-language coupling17. Patients with implanted depth electrodes have performed navigational tasks to study brain oscillations in memory, learning18 and movement19. Depth electrode recordings were also used to study paradigms with otherwise unattainable temporal resolution such as hippocampal evoked activity20, neural activity in the default-mode network21, and the temporal course of emotional processing22. Hudry et al studied patients with temporal lobe epilepsy who had SEEG electrodes implanted into their amygdala for short-term olfactory stimuli matching23. Another group has studied simple limb movements such as hand flexion or unilateral movement of the hand or foot in healthy brain sites from epileptic patients with implanted SEEG24,25.
The studies described above are a small sampling of a very diverse collection of relevant literature. There exists an insurmountable potential to learn and understand how the human brain works using a combination of behavioral tasks and intracranial recordings. While there are other methods for achieving this goal, intracranial recordings possess several benefits including high temporal and spatial resolution as well as access to deeper structures. The authors aim to describe the general methodology for recording from patients with intracranial electrodes during behavioral tasks. However, there are several deterrents and barriers to successfully completing clinical research in patients receiving care. Limitations, confounding effects, and significance of this research will also be identified and explored.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
		</tr>
		<tr>
			<td>InMotion ARM</td>
			<td>Interactive Motion Technologies</td>
			<td>InMotion Arm</td>
			<td><a href="http://interactive-motion.com/inmotion-arm-the-new-standard-of-care/">http://interactive-motion.com/inmotion-arm-the-new-standard-of-care/</a> 
			Equipment our lab used, can use other equipment to collect data</td>
		</tr>
		<tr>
			<td>MATLAB</td>
			<td>Mathworks Inc</td>
			<td>MATLAB</td>
			<td><a href="http://www.mathworks.com/">http://www.mathworks.com/</a> 
			Need version r2007b or higher to run Monkeylogic</td>
		</tr>
		<tr>
			<td>Data Acquisition Toolbox</td>
			<td>Mathworks Inc</td>
			<td>Data Acquisition Toolbox</td>
			<td><a href="http://www.mathworks.com/products/daq/">http://www.mathworks.com/products/daq/</a> 
			Must have to run Monkeylogic</td>
		</tr>
		<tr>
			<td>Image Processing Toolbox</td>
			<td>Mathworks Inc</td>
			<td>Image Processing Toolbox</td>
			<td><a href="http://www.mathworks.com/products/image/">http://www.mathworks.com/products/image/</a> 
			Must have to run Monkeylogic</td>
		</tr>
		<tr>
			<td>Monkeylogic</td>
			<td>Wael Asaad and David Freedman</td>
			<td>Monkeylogic</td>
			<td><a href="http://www.brown.edu/Research/monkeylogic/">http://www.brown.edu/Research/monkeylogic/</a> 
			Free download, must have MATLAB to run</td>
		</tr>
		<tr>
			<td>Chronux&#160;</td>
			<td>Medametrics, LLC&#160;</td>
			<td>Data Processing Toolbox</td>
			<td><a href="http://www.chronux.org/">http://www.chronux.org/</a></td>
		</tr>
		<tr>
			<td>Brainstorm</td>
			<td></td>
			<td>MEG/EEG Analysis Application</td>
			<td><a href="http://neuroimage.usc.edu/brainstorm/">http://neuroimage.usc.edu/brainstorm/</a></td>
		</tr>
		<tr>
			<td>Laptop</td>
			<td>Dell</td>
			<td>Latitude E5530</td>
			<td><a href="http://www.dell.com/us/business/p/latitude-e5530/pd?ST=dell%20latitude%20e5530&amp;dgc=ST&amp;cid=263756&amp;lid=4781504&amp;acd=12309152537461010">http://www.dell.com/us/business/p/latitude-e5530/pd?ST=dell%20latitude%20e5530&#38;dgc=ST&#38;cid=263756&#38;lid=4781504&#38;acd=12309152537461010</a></td>
		</tr>
		<tr>
			<td>NI Card</td>
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performing behavioral tasks in subjects with intracranial electrodes

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in different areas of their brain for the localization of their seizure focus and eloquent areas. After implantation, the patient must remain in the hospital until the pathological area of brain is found and possibly resected. During this time, these patients offer a unique opportunity to the research community because any number of behavioral paradigms can be performed to uncover the neural correlates that guide behavior. Here we present a method for recording brain activity from intracranial implants as subjects perform a behavioral task designed to assess decision-making and reward encoding. All electrophysiological data from the intracranial electrodes are recorded during the behavioral task, allowing for the examination of the many brain areas involved in a single function at time scales relevant to behavior. Moreover, and unlike animal studies, human patients can learn a wide variety of behavioral tasks quickly, allowing for the ability to perform more than one task in the same subject or for performing controls. Despite the many advantages of this technique for understanding human brain function, there are also methodological limitations that we discuss, including environmental factors, analgesic effects, time constraints and recordings from diseased tissue. This method may be easily implemented by any institution that performs intracranial assessments; providing the opportunity to directly examine human brain function during behavior.

In these results we present the analysis of the SEEG data from the limbic system captured in one subject playing the War Task. We can demonstrate that various aspects of the War Task evoke significant gamma-band (40 - 150 Hz) modulation in the limbic system (Figure 1). As seen, in the visual cortex, the presentation of an object on the screen results in a fast latency (~200 msec) wide band response regardless of the task contingency. In addition, there appears to be differences in the duration of the res...

Watch this Scientific Journal Video about Performing Behavioral Tasks in Subjects with Intracranial Electrodes at JoVE.com

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

Patients implanted with intracranial electrodes provide a unique opportunity to record neurological data from multiple areas of the brain while the patient performs behavioral tasks. Here, we present a method of recording from implanted patients that can be reproducible at other institutions with access to this patient population.

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in ...

performing-behavioral-tasks-in-subjects-with-intracranial-electrodes

Research

JoVE Journal

Behavior

11.3K Views.  Cleveland Clinic Foundation. Patients implanted with intracranial electrodes provide a unique opportunity to record neurological data from multiple areas of the brain while the patient performs behavioral tasks. Here, we present a method of recording from implanted patients that can be reproducible at other institutions with access to this patient population. 

Video: Performing Behavioral Tasks in Subjects with Intracranial Electrodes

Study Motor Skill Learning by Single-pellet Reaching Tasks in Mice

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and retrieve food rewards positioned at a specific location, their motor performance (defined as accuracy and speed) improves progressively over time, and plateaus after persistent training. Once such reaching skill is mastered, its further maintenance does not require constant practice. Here we introduce a single-pellet reaching task to study the acquisition and maintenance of skilled forelimb movements in mice. In this video, we first describe the behaviors of mice that are commonly encountered in this learning and memory paradigm, and then discuss how to categorize these behaviors and quantify the observed results. Combined with mouse genetics, this paradigm can be utilized as a behavioral platform to explore the anatomical underpinnings, physiological properties, and molecular mechanisms of learning and memory.

Persistent practice improves the precision of coordinated movements.&#160;Here we introduce a single-pellet reaching task, which is designed to assess the learning and memory of forelimb skill in mice.&#160;

Reaching for and retrieving objects require precise and coordinated motor movements in the forelimb. When mice are repeatedly trained to grasp and ...

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station INBEST

Prolonged and comprehensive monitoring of mice in a home-cage environment provides a deeper understanding of aberrant behavior in murine models of brain diseases. This paper describes the Integrated Behavioral Station (INBEST) as the key component of contemporary behavioral analysis.

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of ...

Uncovering Beat Deafness: Detecting Rhythm Disorders with Synchronized Finger Tapping and Perceptual Timing Tasks

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson&#8217;s disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder).

Behavioral tasks that allow for the assessment of perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) are presented. Synchronization of finger tapping to the beat of an auditory stimuli and detecting rhythmic irregularities provides a means of uncovering rhythm disorders.

A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Measurement of Vibration Detection Threshold and Tactile Spatial Acuity in Human Subjects

Tests that allow the precise determination of psychophysical thresholds for vibration and grating orientation provide valuable information about mechanosensory function that are relevant for clinical diagnosis as well as for basic research. Here, we describe two psychophysical tests designed to determine the vibration detection threshold (automated system) and tactile spatial acuity (handheld device). Both procedures implement a two-interval forced-choice and a transformed-rule up and down experimental paradigm. These tests have been used to obtain mechanosensory profiles for individuals from distinct human cohorts such as twins or people with sensorineural deafness.

Here, we present protocols to determine vibration detection thresholds and tactile acuity using psychophysical methods in man.

Tests that allow the precise determination of psychophysical thresholds for vibration and grating orientation provide valuable information about ...

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

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 ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Behavioral Disturbances: An Innovative Approach to Monitor the Modulatory Effects of a Nutraceutical Diet

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, the traditional ways to monitor behavioral changes in dogs are complicated and not efficient. In the current clinical evaluation, a new, simple monitoring system was used to assess the effectiveness of a specific diet in positively modulating the intense and restless activity of 24 dogs of different ages and breeds. This protocol describes how to easily and rapidly evaluate improvement in a set of symptoms related to generalized anxiety by using a specific sensor, a mobile phone app, a wireless router, and a computer. The results showed that dogs treated with specific diets showed significant improvement in the times spent active and at rest after 10 days (p &lt; 0.01 and p &lt; 0.05, respectively). These dogs also showed an overall significant improvement in clinical and behavioral symptoms. A specific sensor, along with its related hardware, was demonstrated to successfully monitor behavioral changes relating to movement in dogs.

We report a simple approach to evaluate the effectiveness of a specific diet in positively modulating the daily activity and clinical and behavioral symptoms of dogs with evident behavioral disturbances.

In dogs, diets are often used to modulate behavioral disturbances related to chronic anxiety and stress caused by intense and restless activity. However, ...

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...