An Event-Related fMRI Study of Overt and Covert Word Stem Completion

Palmer, Rosen, Ojemann, Buckner, Kelley, and Petersen

Neuroimage, 2001

Introduction

Spoken responses relied on for many neurological and cognitive studiese.g., picture naming, verbal fluency, verb generation,

word-stem completion

fMRI could benefit from the use of prior approaches to question of language processingPreexisting theory and data could help inform work

that uses imaging methods

Unfortunately, using these prior approaches lead us to a major problem

Possibility of motion artifacts and magnetic susceptibility artifacts due to jaw and mouth movement

Could obscure true neural signal changes and lead to misleading activation

Why not have subjects perform the task silently?

Difficult to know that subjects are doing what you have asked them to do

Reaction time and accuracy data cannot be collected

Most importantly, brain activity that underlies silent performance of a language task might differ from activity that occurs when the task is performed aloud

Due to these problems, very few fMRI studies have been done in which spoken verbal responses are used

Exceptions include Barch, Sabb, Carter, Braver, Noll, and Cohen (1999) and Birn, Bandettini, Cox, and Shaker (1999)

Barch et al. (1999)

Block-design fMRI used to make direct comparisons of patterns of activation, susceptibility artifacts, signal-to-noise ratios during tasks done silently or aloud

Obtained interpretable images, but did not image the whole brainRegions near the plane of the throat and mouth were

avoided

Birn et al. (1999)

Block-design fMRI and event-related fMRI were used

Subjects made various brief movements, including saying single words out loud

Region of interest: motor cortex

Birn et al. (1999)

Images contained some movement artifact, but it was possible to minimise this artifact in the event-related paradigm by taking advantage of the different temporal characteristics of the hemodynamic response and the motion-related signal change

Present Study

Uses event-related methods to compare overt and covert visual word stem completionWell studied using functional imaging and positron

emission tomography

Also evaluating the feasibility of obtaining artifact-free images through an analysis of head movement and noise across the time course of the hemodynamic response

Present Study

Within-subject comparisons of covert or overt response mode also allow us to address whether the processing involved in word stem completion differs for silent versus aloud performance

Also address the issue of presentation rate

Methods…Subjects:

5 males, 5 females (mean age = 27.3)

Right-handed

Native English speakers

Methods…Task:

3-letter word stems completed under COVERT instructions (i.e., say the word to yourself and do not move your lips) and OVERT instructions (i.e., say the word aloud) Instructed to minimise head movement while

speaking

Maintained fixation between word stem trials

Methods…Stimuli:

375 three-letter word stems, with at least five different completions

Frequency greater than one per million

Each word stem was presented for 150 ms

Methods…Experimental Design:

Three presentation ratesSlow: 16.8 s between stimulus onsets; 16 word stems

Moderate: average of 9.6 s between stimulus onsets (range of presentation rates = 4.8 s to 24.0 s); 28 word stems

Fast: average of 4.8 s between stimulus onsets (range of presentation rates = 2.4 s to 12.0 s); 56 word stems

Methods

Functional runs lasted approximately 5.5 min, with a 2 min delay between runs

Within each of the Moderate and Fast conditions, intervals between stimuli were generated such that the interval between stimulus n and stimulus n+1 could not be predicted from the interval between stimulus n-1 and stimulus n

Each subject completed 12 runs (two OVERT and two COVERT runs at each of the three presentation rates)

400 trials, 375 word stems; 25 word stems repeated (randomly selected, same word was not repeated in a single run)

Imaging Procedures:Thermoplastic mask1.5 Tesla scannerIn each run, sixteen 8 mm slices were taken at

once, 124-128 times, at a rate of 1 every 2364 ms

Voxel size: 3.75 X 3.75 X 8 mm

Analysis: Preprocessing of Raw Data.

Series of automated steps was used to preprocess the data

Analysis of head position was conducted to determine if there were any runs that contained excessive motion

Adjustments that were used to realign the images (step 3) were used as an index of head movementInspection of these data revealed very few

displacements greater than 0.5 mm in any direction, even for OVERT conditions

Functional data were analysed using an implementation of the general linear model that made no assumptions about the shape of the hemodynamic response

GLM included the 7 MR frames that followed the presentation of the stimulus

Thus, modeled over 16.5 s (7 frames, each lasting 2.36 s)

Analysis: Generation of Activation Images.

Time series was cross-correlated with a three parameter gamma function

Peak percent signal changeTime to response onsetTime to response peak

Z statistical maps based on this cross-correlation at each voxel were generated for each run, for each subject, and then transformed into Talaraich space

Analysis: Generation of Activation Images.

Results

Statistical Images

Z statistical images were created for Overt and Covert stem completion, separately, for individual subjects (6 runs per condition) and averaged across subjects (60 runs per condition)

Interpretable images, relatively free of artifact, were obtained for both types of images

Both contained regions of activation previously observed in PET and fMRI studies of visual word stem completion

Both: Bilateral 6/44, bilateral inferior frontal gyrus, anterior cingulate, bilateral inferior parietal lobe, left fusiform gyrus, right lateral cerebellum

Overt, additionally: bilateral primary motor cortex, medial cerebellum

Statistical images were averaged across subjects and runs

Peak activations with Z scores greater than 7.0 were selected for subsequent analysis

Cutoff was selected because it seemed to capture consistent activation across images of each condition (Overt, Covert, Slow, Moderate, Fast)

Analysis: Selection and Definition of Regions of Interest.

Used these images to define regions of interest by:Manually selecting active pixels surrounding each

peak

Judgements about the extent of each region were made by visual inspection of the image, in an effort to maintain the anatomical contours of the activated region

Analysis: Selection and Definition of Regions of Interest.

Note. BA, approximate Brodmann area; IFG, inferior frontal gyrus; SMA, supplementary motor area. *Values that pass a Bonferroni correction for multiplecomparisons at a significance level of P < 0.05

Regions of interest

Regions of decreased blood flow were also observed in “classic” regions of decreased activation

Now that we’ve defined regions of interest,

Time series from the regions selected were submitted to a 2 (Mode: Overt/Covert) X 3 (Presentation Rate: Slow/Moderate/Fast) X 7 (MR Frame: 1-7) ANOVA

Time X Mode (time course of response has different shape for Overt and Covert conditions)

Time X Presentation Rate (time course of response has different shape for different presentation rates)

Analysis: Regions-based Analysis.

Interactions between Time and Mode:For all regions in which the Mode X Time interaction

was significant (p<.05, uncorrected), magnitude of activation was greater for Overt than Covert respondingBilateral 6/44, anterior cingulate, SMA, bilateral

primary motor cortex, bilateral cerebellum, bilateral thalamus

FIG. 2. Representative time courses of overt and covert word stem completion for a motor-related region (left primary motor cortex) and a nonmotor region (left 6/44). Data were averaged across the three presentation rates. X-axis is time at end of each MR frame.

For the typically motor related regions, the time course was nearly flatfor the Covert condition and peaked for the Overt condition.In other regions, the response was peaked for both conditions, but of greater magnitude in the Overt condition.

Time X Presentation Rate: Response was evident at all presentation rates, but decreased in magnitude as presentation rate increased (representative area shown above)

Comparisons were conducted for regions that showed a significant Time X Presentation Rate interactionInteraction observed for anterior cingulate, right primary

cortex, left 6/44, right inferior frontal gyrus

Comparisons showed that the significant interactions were driven by changes in the overall magnitude of the response and not due to a change in the shape of the response function at different presentation rates

This difference in magnitude of response is consistent with other event-related fMRI studies

Miezin et al. (2000) examined the hemodynamic response in primary visual cortex and primary motor cortex for visual stimuli (with a button-press response) spaced at a range of intervals (20s to 2.5s) comparable to Slow and Fast conditions of the present

study

Miezin et al. observed a 20% reduced amplitude of the hemodynamic response peak in the fast condition compared to the widely spaced condition

Nevertheless, Miezin et al. showed that the properties and shape of the hemodynamic response were consistent across presentation rates

Suggested that the reduction in amplitude might be due to saturation of the hemodynamic response or a change in the underlying neural response

Given that the typical RT in a visual word stem completion task is less than one second, the verbal response should be complete before the onset of the hemodynamic response

Expect that head movement and noise should be greatest in the first MR frame (0-2.5 s following stimulus)

Three analyses carried out to examine Slow presentation condition during Overt and Covert conditions (slow because we don’t have to worry about overlapping hemodynamic responses)

Analysis: Analysis of Speech-related Movement and Noise.

Average head position in each of six dimensions (x, y, and z planes, in translation and rotation) was computed for the three subjects that had the most head movements This value was subtracted from the actual head

position at each of the seven MR frames

Absolute values of the residuals were averaged across runs and subjects for each of the seven MR frames, separately for each Mode condition

Subjected to a 2 (Mode: Overt/Covert) X 7 (MR Frame: 1-7) ANOVA

Analysis I

Head movement: Analysis of head position revealed very little for the six dimensions

No disproportionate movement in the first MR frame of the Overt condition relative to other MR frames

Brain regions that are not active during a task should produce a zero percent signal change in the hemodynamic response function

Any deviation from zero should be due to noise

Used deviations from zero to assess noise in the Overt compared to the Covert condition

Analysis II

Two brain regions were selected for this analysis

Relatively high in the brain, where susceptibility effects from mouth movement should be minimal and relatively low in the brain, where mouth movement should have the greatest effect

Both were nonactive regions of the anterior right frontal cortex (as determined by examination of time courses)

Regions were at the border between gray matter and white matter to maximise effects of movement

Analysis II

Significant main effects of Region (High/Low), Mode (Overt/Covert), and a significant interaction between Region and Mode

Mean deviation from zero was greater in the Overt condition in the low brain region than mean deviation from zero in any of the other mode or region conditions

For each of the 10 subjects, estimates of model fit were extracted from each of the regions used in the time course analysis

Residual values were computed separately for the Overt and Covert conditions at each of the MR frames following the stimulus

Absolute values were averaged across subjects and subjected to a 2 (Region: High/Low) X 2 (Mode: Overt/Covert) X 7 (MR Frame: 1-7) ANOVA

Analysis III

In the analysis of model fit residuals, there were significant main effects of Region and Mode and a significant interaction between Region and Mode

Similar to results of the time course analysis, mean residual values for the Overt condition in the low brain region were greater than residuals for any of the other three mode/region conditions

Discussion

Risk of motion artifacts and magnetic susceptibility artifacts in images obtained from block-design fMRI have prevented widespread use of fMRI for tasks that use overt speech

Yetkin et al. (1995) compared images from overt and covert performance of a verbal fluency task during a block-design fMRI experiment

Similar regions of activation were reported, but significantly more artifacts were obtained in the overt than in the covert condition

Phelps et al. (1997) tried to localise activation in the prefrontal cortex during an overt verbal fluency taskUsable images were obtained from only 5 of 11

subjects and images were usable only from the superior prefrontal cortex

Small et al. (1996) used a block-design fMRI to replicate activation in the left posterior superior temporal gyrus during word reading

A bite plate was required, so this type of procedure wouldn’t be useful for RT studies or for studies in which clear articulation is necessary

Discussion

Present study assessed the feasibility of using fMRI to study tasks with overt verbal responses

Patterns of activation observed in the present study correspond with those reported in previous studies

Results suggest that event-related methods are useful in minimising artifacts due to overt speech

In the present study, little movement-related artifact was observed (mainly in the low brain region)Subjects moved their heads only minimallyNoise was no greater in the first MR frame than in the

subsequent frames, suggesting that it was not the actual motor movements associated with saying a word that produced noise

Suggest that the noise might be due to changes in the vocal apparatus