Neurophysiological Mechanisms of Language Comprehension

Study Overview
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Brief Summary
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First, in a recording-only self-paced reading experiment, patients with epilepsy undergoing intracranial monitoring for clinical purposes will read or listen to sentences presented to them one word at time while the investigators simultaneously record neural activity through intracranial electrodes that are implanted for clinical purposes (see subject populations). At the end of the sentence, the subjects have to indicate how they comprehended the sentence by selecting which of several pictures matches the sentence they just read. Behavioral measures that the investigators record and analyze are their response times to advance to each next word in the sentence, and which picture they chose for each sentence. These behavioral measures are compared against the neural activity simultaneously recorded as they are made. Then, in a later session, the same participants will participate in a task-related stimulation experiment. This follows the exact same design as the recording-only reading experiment, the only difference is that on some trials, at controlled moments during the sentence presentation intracranial electrical stimulation is delivered through adjacent intracranial electrode contacts. The investigators will examine the effect of this stimulation on the subjects comprehension of the sentences measured by their behavior, and on the simultaneously recorded neural activity.

Detailed Description
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All experiments and recordings will take place in the University of Alabama at Birmingham (UAB) Epilepsy Monitoring Unit (EMU). All electrodes being used to gather data are in place through standard of care to treat the patient's epilepsy by monitoring neural activity to guide an upcoming respective surgery. In all experiments, neural activity will be recorded from the standard of care electrodes using either a high-fidelity, FDA-approved Neuralynx Atlas amplifier system (Bozeman, MT) or a standard-of-care recording system (Natus Quantum Recording System, Pleasanton, CA) that is used normally to monitor seizure activity for clinical purposes during the patient's hospital stay. In the task-related stimulation experiment, stimulation will be delivered with a standard of care electrically isolated stimulator (Nicolet Cortical Stimulator, Natus, Pleasanton, CA). Recording-only word-by-word task. Participants are asked to read and comprehend sentences presented one word at a time. Participants advance through the sentence at their own pace by pressing a button to advance to each next word of the sentence. At the end of each sentence, participants are presented with 4 pictures, and their task is to choose which of the 4 pictures corresponds to the sentence they just read. Three sentence types are presented: Object relative sentences (e.g. The cat that the dog chased was brown), Subject relative sentences (The cat that chased the dog was brown) and control sentences (The brown cat chased the dog). The 4 pictures simultaneously probe patient/agent assignment (i.e. who chased whom?) and complement-noun assignment (was the cat or the dog brown?). 1 of the 4 pictures is correct, 1 picture reflects a patient-agent error, 1 reflects a complement-noun error, and 1 reflects both errors simultaneously. Stimulation task. Subjects will perform a word-by-word sentence-reading task as before, only for this task on some object relative sentence trials intracranial stimulation is applied at the phrase boundary in the middle of the sentence. For example, this would be the word chased in the object relative sentence The cat that the dog chased was brown. Stimulation parameters. Intracranial stimulation is delivered at 50 Hz for 1 second. This stimulation parameters are designed to interrupt local processing when delivered to areas outside of primary motor and sensory cortices. The investigators will choose which electrodes to stimulate based on the anatomical locations of recording sites for that patient and based on preliminary analyses of recorded activity in recording-only sessions before the stimulation session. Intracranial stimulation will be performed with simultaneous intracranial recording. Stimulation sessions need to be minimized in length to avoid patient fatigue and other effects from too much stimulation. In our preliminary data the investigators have found that the investigators can acquire 8 stimulation trials in 2 different stimulation locations for a given patient. The investigators ideally will choose one left Inferior Frontal Gyrus (IFG) and one left Superior Temporal Sulcus (STS) electrode to stimulate to the extent that one or both are available for a subject. The investigators stimulate the most difficult sentences, object-relative sentences, to maximize the chances of observing an effect. The investigators will pair this with an equal number (8) of non-stimulated object-relative sentences. When possible, the investigators will include 8 subject-relative and 8 control sentences, both without stimulation to include variety in the types of sentences given in the stimulation session. The stimulation task will be performed either with a constant rate of word presentation (500 ms per word) through-out all of the sentences, or performed in a self-paced manner as described above for the recording-only word-by-word task. All participants will complete the same procedures. Participants will perform any recording only tasks first, which will occur when they are able and willing to after they have recovered from the surgery, typically 2 days after the implantation surgery. Participants will perform the stimulation task in co-ordination with the epileptologists at the EMU in the same sessions when stimulation mapping occurs for clinical purposes. This typically occurs at the end of the patient's stay in the EMU when the patients are on full doses of anti-seizure medication.

Official Title
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Neurophysiological Mechanisms of Language Comprehension

Conditions
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Language Disorders

Intervention / Treatment
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* Behavioral: Sentence Type
* Other: Direct brain stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 and older Undergoing standard of care stereo Electro Encephalogram (sEEG) or Electro-Corticogram (ECoG) monitoring Able to competently perform control trials of the task Exclusion Criteria: Age less than 18 years Unable to competently perform control trials of the task

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intracranial patients<br>All participants with epilepsy undergoing intracranial monitoring for clinical purposes will be approached to participate in an experiment that is recording-only and an experiment that involves stimulation with simultaneous recording. | Behavioral: Sentence Type<br>* Subjects read different types of sentences (object-relative, subject -relative and control sentences) to observe how that sentence affects their intracranially recorded neural activity.<br>Other: Direct brain stimulation<br>* On some trials the investigators will apply intracranial electrical current through the electrodes implanted in the participants and observe the effect this has on their behavior (which picture they choose at the end of the trial) and the effect this has on their neural activity that the investigators record simultaneously through-out the experiment.<br>* Other names: Intracranial stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral Response- Picture Choice | The investigators will observe which picture the participant chooses at the end of each trial. The participant's choice will be measured by a touch screen that the patient touches to make their choice. The unit of measurement is the percentage of trials per condition studied in which participants choose the correct picture, versus the percentage of trials per condition studied in which participants choose the picture that reflects a patient-agent error (which reflects incorrect assignment of the patient versus agent roles of the nouns in the sentence), versus the percentage of trials per condition studied in which participants choose the picture that reflects a complement error (which reflects that the subjects mistakenly applied an adjective to the wrong noun in the sentence), versus the percentage of trials per condition studied in which participants choose the picture that reflects both a patient-agent and a complement error. | Measured immediately after the intervention | 
| Behavioral Response - Self-paced word response time for words presented before electrical stimulation | While subjects perform self-paced reading experiments, this is the amount of time they spend on each word of the sentence before moving on to the next word of the sentence. | Outcomes will be measured immediately before the intervention | 
| Behavioral Response - Self-paced word response time for words presented concomitant with electrical stimulation | While subjects perform self-paced reading experiments, this is the amount of time they spend on each word of the sentence before moving on to the next word of the sentence. | Outcomes will be measured concomitant with the intervention | 
| Behavioral Response - Self-paced word response time for words presented after electrical stimulation | While subjects perform self-paced reading experiments, this is the amount of time they spend on each word of the sentence before moving on to the next word of the sentence, for words presented after electrical stimulation | Outcomes will be measured immediately after the intervention | 
| Neural activation before electrical stimulation | With the electrodes implanted in the patient as a standard of care, the investigators will measure the neural activation at each electrode as assessed by the high gamma power present in that recorded channel | Outcomes will be measured immediately before the intervention | 
| Neural activation concomitant with electrical stimulation | With the electrodes implanted in the patient as a standard of care, the investigators will measure the neural activation at each electrode as assessed by the high gamma power present in that recorded channel | Outcomes will be measured concomitant with the intervention | 
| Neural activation after electrical stimulation | With the electrodes implanted in the patient as a standard of care, the investigators will measure the neural activation at each electrode as assessed by the high gamma power present in that recorded channel | Outcomes will be measured immediately after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurophysiological, Language Comprehension, Direct brain stimulation, Self-paced reading