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7. Description of project

(A) Research Description

Objectives and expected outcomes. The proposed experiments extend our studies of the neural mechanisms responsible for speech production performed during the previous 10 years of this grant, R01 DC02852 (BU IRB protocol #918E). These experiments involve the same aims and general methods as our previous experiments under this protocol. The new application includes 7 new fMRI studies and 7 new psychophysical studies.

The primary goal of this research project is the continued development, testing, and refinement of a computational model describing the neural processes underlying speech. We believe this model, called the DIVA model, provides the most comprehensive current account of the neural computations underlying speech articulation, including treatment of acoustic, kinematic, and neuroimaging data. In the upcoming budget period, we propose to focus on the neural circuitry involved in auditory feedback-based control of speech movements. The project involves 3 closely related subprojects aimed at key issues concerning auditory feed-back control of speech:

(1) Control of prosodic aspects of the speech signal. This subproject combines neural modeling with psychophysical and functional magnetic resonance imaging (fMRI) experiments to investigate the neural mechanisms responsible for the control of word- and phrase-level prosody. The psychophysical experiments are designed to identify the degree to which prosodic cues are controlled independently vs. in an integrated fashion. The fMRI experiments are designed to identify the neural circuitry responsible for feedback-based control of prosodic cues. The modeling project involves modification of the DIVA model to incorporate mechanisms for controlling prosody. Simulations of the model performing the same speech tasks used in the experiments will be compared to the experimental results to test the model’s account of the neural circuitry responsible for prosodic control.

(2) Representation of speech sounds in auditory cortical areas. In this subproject, we propose fMRI experiments and modeling work designed to further our understanding of the representation of speech sounds in the auditory cortical areas. This issue is central to the DIVA model, which utilizes an auditory reference frame to store speech sound targets for production. The modeling work will extend our model of auditory cortical maps (currently distinct from the DIVA model) and integrate it with the DIVA model. The modeling work will be guided by two fMRI experiments investigating important aspects of the neural representation of speech sounds: phonemic vs. auditory representations and talker-specific vs. talker-independent representations.

(3) Integration of feedforward and feedback commands in different speaking conditions. In this subproject, we propose to investigate the hypothesis that decreased use of auditory feedback control in fast speech and increased use in clear (carefully articulated) and stressed (emphasized) speech are responsible for differences in articulatory and auditory variability in the different speaking conditions. We propose an fMRI experiment to investigate fast, normal, clear, and stressed speech to test two model-based hypotheses regarding brain activity in the different conditions: (i) fast speech will lead to increased inhibition of auditory and somatosensory areas (indicative of less use of feedback control) when compared to normal speech, and (ii) clear and stressed speech will lead to more activation in the auditory and somatosensory cortical areas than normal speech due to increased reliance on feedback control.

The modeling work proposed in the three subprojects will be integrated into a single, improved version of the DIVA model, thus insuring that they provide a unified account of the neural bases of auditory feedback control of speech. We believe the resulting model will be useful to researchers studying communication disorders by providing a much more detailed description of the functional and neuroanatomical underpinnings of normal speech than currently exists, and by providing a functional description of what to expect when part of the neural circuitry malfunctions. We believe this improved understanding will ultimately help guide improvements to diagnostic tools and treatments for speech disorders.

Experimental design. We anticipate the need for a total of approximately 245 subjects for the 7 fMRI and 7 psychophysical experiments described in our research proposal. All experiments involve the subject speaking a word or short list of words, either with normal auditory feedback or perturbed auditory feedback. The 7 fMRI experiments each involve a single fMRI imaging session per subject. One fMRI experiment (Experiment 1 in Section D.2 in the application) requires a psychophysical session prior to the imaging session for each subject in order to generate the appropriate stimuli for the fMRI experiment.

MRI sessions. fMRI is a technique for detecting changes in brain activation during perceptual, cognitive, or motor tasks by measuring changes in local blood flow. Each session starts with the subject lying on the table of the MRI scanner. Blankets and pillows are used to help insure the comfort of the subject, which is very important for preventing unwanted movements during the 2-hour scanning session. The subject’s head is immobilized using foam pads inserted between the subject’s head and the head carriage of the scanner. The table is then slid into a large magnet with a bore of approximately 1 meter. During the first fifteen minutes or so of scanning, a conventional high-resolution anatomical scan is obtained to allow localization of brain structures. After these localizing images are obtained, functional images are obtained using the high-speech function of the MRI scanner, which is capable of measuring changes in blood flow that correlate with brain function. High-speed images are collected during 4 to 8 experimental runs, each lasting approximately 6 to 12 minutes. During these runs, subjects will be asked to attend to auditory stimuli, attend to visual stimuli, produce speech, and/or lie silently in the scanner. Auditory stimuli are presented via a stereo headset at a volume deemed comfortable by the subject. Visual stimuli are projected onto a screen that the subject views through a mirror. The flashing pattern displayed by the video projector does not present any health hazards to normal volunteers. Subjects with a history of epilepsy or other seizure disorder will be excluded from studies involving visual stimuli. Subjects with corrected-to-normal vision who participate in experiments with visual stimuli will be provided with non-magnetic corrective glasses, available at the MGH MRI facility. After the high-speed imaging runs are completed, a few additional conventional images are collected to help with registering the functional data with the anatomical data. The entire imaging session lasts approximately 2 hours. IRB approval from the Massachusetts General Hospital IRB (Partners) is being sought in parallel with this application, and the Partners approval letter will be forwarded to the BU IRB when it is available. This protocol will be an amendment to our existing, currently active Partners protocol that covered the first 10 years of the grant.

Psychophysical sessions. The 7 psychophysical experiments proposed in Section D.1 of the application involve a sensorimotor adaptation paradigm in which subjects repeatedly pronounce a list of words while their auditory feedback is gradually perturbed (by shifting either the pitch or loudness of their own speech as heard through headphones). Stimuli will be presented orthographically on a computer display. These psychophysical studies will be run at Northeastern University under the supervision of Dr. Rupal Patel. Northeastern University human subjects approval is being sought in parallel with the current application; the Northeastern University approval letter will be forwarded to the BU IRB when it is available.

In addition, fMRI experiment 1 in Section D.2 involves a psychophysical session prior to the fMRI session for each subject that will be performed at Boston University. During this session the subject will first produce a small number of words presented on the screen visually. Recordings of these words will then be manipulated to produce speech sound continua that are then presented to the subject in an auditory identification task. The purpose of this session is to determine the auditory stimuli that will be used in the subsequent fMRI session.

An entire psychophysical session is expected to last between 0.5 and 1.5 hours. Each subject will participate in only one session. Subjects will be required to wear headphones during the psychophysical sessions. 1.5 hours. The psychophysical sessions involve no known or expected risks.

Materials and procedures. For the MRI sessions, we will use a 3 Tesla Siemens scanner at the Massachusetts General Hospital Charlestown location (Building 149, 13th Street, Charlestown, MA). Electronic data will be transferred from MGH to the Boston University Department of Cognitive and Neural Systems password-protected computer facilities, where all data analysis will take place. Psychophysical sessions will be performed at the Department of Cognitive and Neural Systems (677 Beacon Street, Boston, MA). Computer workstations will be used to present the visual stimuli and/or auditory stimuli. These workstations will also be used to record the subjects’ verbal responses. Auditory stimuli will either be played over a computer speaker or through headphones at a comfortable listening level.

(B) Subjects will be healthy individuals with no history of speech or hearing disorders. All subjects will be native speakers of American English between the ages of 18 and 55, with no form of implant that involves magnetic or electric parts. Because brain lateralization for different speech tasks is among the issues being studied, we will use right-handed subjects to maximize the likelihood that the subject has left hemisphere dominance for language. A total of approximately 245 subjects will be needed for the experiments proposed in our research plan: 20 subjects (including pilot subjects) in each of 7 fMRI experiments, and 15 subjects (including pilot subjects) in each of 7 psychophysical experiments. In experiments involving visually presented stimuli, subjects will be required to have normal or corrected-to-normal vision (corrected using non-magnetic glasses available at the MGH NMR Center). To the extent possible, subjects will represent the gender and racial/ethnic composition of the general population.

(C) Subjects will be told that the experiment concerns the brain processes involved in speech production. Subjects will be recruited by advertising in the form of posters and electronic mail messages. When an individual volunteers to be a subject, the experimental protocol will be explained in detail verbally and she/he will be given a copy of the consent form to read and sign. The subject will be told that the experimenters will answer any questions about the procedure (except about aspects of the design or hypotheses that might influence their performance).

(D) Informed consent will be obtained prior to each experimental session by the experimenter (Professor Guenther, a postdoc or graduate research assistant).

(E) Subjects derive no benefit from the procedures except payment. However, risk is negligible and their participation will contribute very useful information concerning the mechanisms of speech production. Thus the risk/benefit ratio is negligible. Subjects for fMRI experiments will be paid $100 for an experimental session lasting approximately 2 hours. Subjects will be paid $10 per hour for participation in the psychophysical portions of the study.

(F) The planned procedures involve unlikely and negligible risk. Magnetic resonance imaging with a 3 Tesla magnet is a commonly employed clinical technique with no known adverse effects. Subjects will be screened to insure that they do not have any intracerebral vascular clips or any electrically, magnetically, or mechanically activated implants such as cardiac pacemakers, and they will be warned about bringing any magnetic materials into the imaging room. Subjects will also be excluded if they suffer from severe claustrophobia. It is possible that subjects may suffer from physical discomfort due to lying still in the scanner for as long as two hours. This risk will be minimized by attending to the subject’s comfort with pillows and blankets before the subject is slid into the magnet. Subjects will also be notified that they can signal the experimenter to remove them from the scanner if they are experiencing discomfort of any kind (the experimenter can see the subject through a glass partition throughout the experimental session).

(G) Subject confidentiality will be protected by not using names or initials in published reports. All data will be stored on password-protected computers or on CDROMs that will be marked with an identification number rather than the subject’s name. The CDROMs will be kept in a locked room.

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