Neurophysiological Mechanisms of Language Comprehension

Overview

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.

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 will be asked to perform language tasks that require them to comprehend and respond to stimuli by pressing a button or touching the screen on a laptop, or by saying their response out loud with their voice recorded. Stimuli will be presented auditorily or visually in the form of words or pictures. For example, in a word-by-word reading task, patients will be asked to read and comprehend sentences or sentence fragments presented one word at a time. Each word will be presented visually or auditorily. Participants may perform this version of the task either with self-pacing- where the participant presses a button to determine when each word in the sentence appears- or computer-pacing- where the timing of words presented are pre-determined and controlled by a computer administering the task. In another task, participants will be asked to listen to and comprehend stories. At the end of some or all sentences, sentence fragments, or stories, participants will be asked questions about the stimuli to ascertain their understanding of the stimuli, for example by presenting different pictures to the participant and asking them to choose which of them matches the sentence they just read. Patient volunteers will perform this task while we record intracranial neural activity from the language network. As another example, in a picture naming task patients will be shown pictures at a fixed speed and asked to say the name of each picture out loud into a microphone as soon as they can. Stimulation pulse connectivity test. Stimulus pulses at precise time intervals will be delivered across adjacent electrode contacts at a series of electrode sites while simultaneously passively recording neural activity at all other electrodes. Pulse timings will be single pulses at randomly jittered times, or pairs of pulses delivered across a range of time intervals between pulses in a pair that vary in a controlled fashion from very fast (\< 1 msec) to long (\~100 msec) time intervals. No task is required of the participant while this takes place, and the participant will typically be resting or engaging in other activities while this happens. The simulation pulse connectivity test will be performed during their hospital stay post-surgery, typically 2 days or longer after the implantation surgery. Stimulation task. In this task, participants perform the word-by-word language task as described above , however on some trials we apply disruptive stimulation at controlled moments during the stimulus (for example at phrase boundaries) to electrode contacts of interest. This task will be administered by a computer. Participants may perform this version of the task either with self-pacing- where the participant presses a button to determine when each word in the sentence appears- or computer-pacing- where the timing of words presented are pre-determined and controlled by a computer. Stimulation will be delivered concomitant with the presentation of certain pre-determined words on certain pre-determined sentences for a pre-determined duration. All stimulation is applied in a safe setting within safe limits. First a threshold amplitude is established at a current strength at which after-discharges do not occur, all under the supervision of a trained epileptologist. If after-discharges occur, the current is lowered. Stimulation uses 50 Hz pulse trains for a maximum of 2 seconds at a time, following the same procedure used in the standard-of-care stimulation mapping procedure. For additional safety, stimulation will only be applied at one moment during a given sentence. All participants will complete the same procedures. Participants with epilepsy 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. Before or after completing the standard 1 hour block of the recording-only language tasks, participants will be informed that they can conduct additional recording-only research sessions during the length of their stay if they are interested to do so. Participants will be informed that as with any research, the existence, timing and duration of any supplemental research blocks will be performed entirely at their discretion. Participants will be informed that during any research block, participants will be free to pause, postpone or end any supplemental block should they choose to. Participants will perform the tasks involving stimulation (the stimulation pulse connectivity test and the task-related stimulation experiment) in coordination with the epileptologists at the EMU in the same sessions when stimulation mapping occurs for clinical purposes or in a separate session shortly following the clinical stimulation after the patient takes a break, which typically occurs at the end of the patient's stay in the Epilepsy Monitoring Unit (EMU) when the patients are on full doses of anti-seizure medication. The duration of all experimental sessions are always at the participant's discretion, which will be communicated to the participant during the consenting process. The target duration of a session is 1 hour, which will likewise be communicated to the participant during the consenting process. Most experimental sessions run will be that length. In the final day before the explantation surgery when future sessions during the participants stay are not possible and further recording will be beneficial to the study, at the participant's discretion the experimental session may be extended beyond that length, so long as the participant agrees to participate, with appropriate breaks between experimental task blocks offered to the participant at a minimum of every 30 minutes. This session duration refers to the cumulative length of all of the experimental tasks described in this protocol (e.g. task-related stimulation experiment, recording-only language task, etc.).