Performing Behavioral Tasks in Subjects with Intracranial Electrodes
October 2nd, 2014
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.
The overall goal of the following experiment is to assess how the brain encodes decisions by playing the card game war. This is achieved by having the patients play a decision-making game while recording brain activity from multiple intercranial electrodes that have been surgically implanted for clinical purposes. As a second step, the data is analyzed offline to interpret the findings.
Results are obtained that show significant gamma band modulation in the limbic system based on power spectrum analysis. The main advantage of this technique over others like it, such as FMRI, PET or MEG, is that it offers both high spatial and temporal resolution while others offer only one or the other. So this method can help answer some key questions in the neuroscience field involving cognitive e motor control, as well as some key questions in brain connectivity.
Well, it's important when conducting these experiments to be both flexible and patient. As the patients may need to eat meals, they may have clinical appointments where they could possibly have a seizure. This method is designed to provide insights into how the brain encodes the decisions.
It can be also applied to different brain functions such as language function or motor memory. The reason why we are doing this experience, because we have a large number of patients that we implant with throats and technique, that's also known as SEG. So we implant areas that were never implanted before in order to localize the seizures, and we can take the opportunity to study those areas.
Also, you doing this unique and very interesting research Begin by evaluating patients with refractory epilepsy in consideration for intracranial electrode implantation. If the patient is a good candidate for the invasive surgery, analyze the patient's existing MRI, PET and Meg, along with the seizure pathology in order to optimize placement of the electrodes. Next, identify eligible patients per the approved IRB protocol based on the inclusion and exclusion criteria.
Then meet with the patients in the clinic and obtain written and informed consent. Prior to any research activities. Explain the study to the subject and emphasize that participation is strictly voluntary and will in no way impact clinical care.
Also, inform the patient that their information will remain anonymous and confidential and that they may cease participation in the study at any time. Under no consequence, the behavioral system includes an FD, A approved robotic arm for patient interaction, a laptop computer to control the behavioral program, a monitor for presenting the task stimuli to the patient and a data acquisition system to store the electrophysiological and behavioral data before bringing the equipment into the patient's room first, ensure that there is sufficient space available as well as access to the necessary outlets. Also, check that all equipment and wires are ready to expedite the setup.
When the patient is ready, bring the behavioral system into the room and begin booting up the behavioral system and robotic arm. Connect the digital event marker output from the behavioral computer to the DC channels of the Electrophysiological acquisition system. This will time lock the recorded stereo electroencephalography signals with behavioral event markers.
It is best to use a separate electrophysiological acquisition system designated for research purposes as shown here. Next, calibrate the robotic arm and position it such that the range of motion is comfortable for the patient. Once all equipment is in place, take precautions so that the patients do not harm themselves in the event of a seizure.
During the task, ensure that the emergency stop buttons are easily accessible by the researchers throughout the behavioral task. After the completion of the rig setup and calibration of the interface device, explain the behavioral task to the patient and have the patient practice the task. We used a behavioral task similar to the children's game war.
Ask the patient to make wagers as to whether their card is greater than the computer's card. So we're gonna play the game before against the computer. So essentially in this task, it's like the kids game of war where you're trying to beat the computer.
But in this case, to make it easier, we use the two card, the four card six, the eight, and the 10 card instead of any face cards and the the way the game works. If you think you're gonna win, you bet a high wager. If you think you're gonna lose, you bet a low wager and you make your bet by moving this robotic arm to hit a target on the screen.
And if you win, you, if you win, you win the money. If you lose, you lose the money. The choice of the wager is based on the patient's perception of the relative value of their card.
We simplified the game by only using cards of one suit and limiting the deck to the 2, 4, 6, 8, and 10 numbered cards. During the task. Show a fixation queue on the screen for 350 milliseconds.
Ensure the patient holds the cursor over the fixation mark to initiate the task. Next, the stimulus should be presented for 1000 milliseconds. Allow the patient to see their card with the computer's card next to it face down.
Following the card's disappearance. Show a go queue 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.
Randomized the wager position from trial to trial to ensure that there is no bias based on position After the wager has been selected, there should be a delay followed by a revelation of the computer's card. Observe whether the trial was a win, lose, or draw and how much was won or lost. Allow the patient to practice until they're confident in their performance and have no questions about the task before recording.
First, verify that the settings on the acquisition system are appropriately selected and assured. If the patient is ready, then 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.
Now begin the task while recording the patient performing the task. We ask the patient to perform the task for 30 minutes. The sampling rate of the robotic arm system should be one kilohertz and that of the SEEG recording system two kilohertz.
After the acquisition session, analyze the data by first de-identifying the recorded SEEG data to ensure that the patient's information remains confidential and that data is submitted anonymously. Then obtain the coordinates of the electrode locations from the postoperative ct and preoperative MRI finally apply signal analysis methods to analyze the event dependent brain activity modulation. Here you can see a power spectrum of activity relative to three different epics in the war task.
The first row depicts the activity of the inferior frontal gyrus, and the second row depicts the activity of the visual cortex. The times zeros of the graphs in each column represents the appearance of bet options, the appearance of positive reward, and the appearance of negative reward. When the subject makes bet the inferior frontal gyrus does not significantly changed its activity.
In contrast, the associated visual cortex has a significant change in the 60 to 100 hertz frequency range, starting approximately 125 milliseconds after the instruction. When the subject wins a hand, there is a significant narrow band modulation in the 40 to 50 hertz frequency band in the inferior frontal gyrus. After about 250 milliseconds, again, the associate of visual cortex has a significant change in the 60 to 100 hertz frequency range, starting approximately 125 milliseconds.
After instruction. Here, the subject has lost the hand. Unlike the wind hand, the inferior frontal gyrus does not respond while the associative visual cortex, once again has a significant change.
So it's important to remember when trying to attempt this procedure that you should always maintain the patient's confidentiality, the comfort of the patient, and to respect the patient's wishes if they choose not to participate. At any time in this procedure Following the procedure, the data can be analyzed with multiple methods to investigate precise nature of the brain communication. Therefore, the data can be used to test many different hypothesis.
The data we've collected in these experiments can be used by a variety of different scientists, for instance, neuroscientists as well as behavioral and computational scientists. After watching this video, you should be able to perform behavioral tasks in patients implanted with SEEG electrodes In the Epilepsy Monitoring Unit, the task design can be modified to study many different modes of human behavior and disease. Initially, it was a little difficult to set up everything, select the patients, get the correct task, but at the end, it was a very productive day.
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Overview
This study investigates how the brain encodes decisions through a card game while recording brain activity from implanted electrodes. The method allows for high spatial and temporal resolution, providing insights into cognitive and motor control.
Key Study Components
Area of Science
- Neuroscience
- Electrophysiology
- Behavioral Analysis
Background
- Intracranial electrodes enable direct recording of brain activity.
- Patients perform behavioral tasks during data collection.
- High spatial and temporal resolution is crucial for understanding brain function.
- This method surpasses traditional imaging techniques like FMRI and PET.
Purpose of Study
- To assess decision-making processes in the brain.
- To analyze brain activity during a card game.
- To explore brain connectivity and cognitive control mechanisms.
Methods Used
- Patients played the card game war while brain activity was recorded.
- Data was collected from multiple intracranial electrodes.
- Offline analysis was conducted to interpret the findings.
- Power spectrum analysis was used to assess gamma band modulation.
Main Results
- Significant gamma band modulation was observed in the limbic system.
- The technique provided insights into decision-making processes.
- High-resolution data revealed important aspects of brain connectivity.
- Results contribute to understanding cognitive and motor control.
Conclusions
- This method enhances our understanding of brain function during decision-making.
- It offers a reproducible approach for future research in neuroscience.
- Findings may inform clinical practices and further studies in brain connectivity.
Frequently Asked Questions
Executive Industry Relevance
Intracranial electrode recordings in human patients provide a unique opportunity to directly link neural activity with complex decision-making behaviors, offering high spatiotemporal resolution that bridges the gap between invasive animal studies and non-invasive human imaging. This approach enables mechanistic de-risking of target validation by revealing real-time brain network dynamics during cognitive tasks, supporting predictive confidence in early discovery stages. The method’s applicability to reward encoding and cognitive control pathways aligns with therapeutic areas involving neuropsychiatric and neurodegenerative disorders, enhancing translational continuity from discovery to preclinical validation.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by correlating intracranial electrophysiological signals with behavioral outputs in reward-based decision-making tasks.
- Operational Value: Provides direct human neural readouts that reduce reliance on surrogate biomarkers and improve target engagement assessment.
- Predictive Value: Supports biological de-risking through observation of gamma band modulation in limbic and frontal circuits during cognitive processing.
Screening & Assay Development
- Assay Readiness: Establishes standardized behavioral paradigms (e.g., card game war) synchronized with electrophysiological acquisition for reproducible neural response measurement.
- Quantitative Outputs: Enables power spectrum analysis of gamma band activity (40–100 Hz) as a quantifiable readout of cognitive engagement and reward processing.
- Scalability: Allows multiple behavioral tasks to be performed in the same subject, increasing data yield per implantation window and supporting cross-task comparisons.
Translational & Preclinical Research
- Disease Relevance: Leverages patients with refractory epilepsy to study neural circuits involved in decision-making, which are often disrupted in addiction, OCD, and frontotemporal dementia.
- Translational Continuity: Facilitates direct comparison of human intracranial data with preclinical models, strengthening target validation and mechanistic insight.
- Risk-Adjusted Advancement: Identifies conserved neural signatures of reward prediction error that can inform biomarker selection for early-phase clinical trials.
Pipeline & Workflow Integration
The method integrates into the discovery continuum by providing early-phase mechanistic insights into cognitive circuits, informing target selection before lead identification and enabling preclinical models to be benchmarked against human neural dynamics.
- Discovery Biology: Supports hypothesis testing of neural substrates involved in value-based decision-making and cognitive control through time-locked electrophysiological recording.
- Screening: Delivers assay-ready, standardized behavioral-electrophysiological paradigms with quantifiable spectral outputs suitable for high-content neural screening.
- Analytics: Generates power spectrum and event-related potential metrics that allow comparison of brain activation patterns across task phases (e.g., bet selection, reward, penalty).
- Translational Research: Connects findings to disease-relevant circuits (e.g., limbic-prefrontal interactions) with implications for neuropsychiatric drug development.
- Enterprise Reuse: Establishes a reusable platform for probing multiple behavioral domains (language, motor memory, decision-making) within the same patient cohort.
Operational & Enterprise Impact
- Scientific Value: Delivers mechanistic insight into human brain function during behavior, reducing ambiguity in target validation and pathway elucidation.
- Operational Value: Enables reproducible, time-synchronized recording of neural and behavioral data using standardized equipment setups (robotic arm, event marking, dual-sampling acquisition).
- Strategic Value: Improves go/no-go decisions by providing direct evidence of target engagement in distributed neural networks during cognitive tasks.
- Portfolio Impact: Supports risk-adjusted prioritization of targets modulating fronto-limbic circuits involved in reward processing and impulse control.
Implementation Considerations
- Requires expertise in electrophysiology, behavioral neuroscience, and clinical coordination with epilepsy monitoring units.
- Dependent on access to intracranial electrode implants and synchronized data acquisition systems capable of dual-kilohertz sampling.
- Necessitates cross-team standardization for task design, event marking, and offline signal processing pipelines.
- Must account for environmental noise, analgesic effects, time constraints, and recordings from epileptogenic tissue as practical limitations.
- Depends on IRB-approved protocols and informed consent processes that prioritize patient safety and voluntary participation.
