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

1. An Event-Related fMRI Study of Overt and Covert Word Stem Completion Palmer, Rosen, Ojemann, Buckner, Kelley, and Petersen Neuroimage, 2001

2. Introduction • Spoken responses relied on for many neurological and cognitive studies • e.g., picture naming, verbal fluency, verb generation, word-stem completion • fMRI could benefit from the use of prior approaches to question of language processing • Preexisting theory and data could help inform work that uses imaging methods

3. 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

4. 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

5. 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)

6. 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 brain • Regions near the plane of the throat and mouth were avoided

7. 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

8. 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

9. Present Study • Uses event-related methods to compare overt and covert visual word stem completion • Well 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

10. 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

11. Methods…Subjects: • 5 males, 5 females (mean age = 27.3) • Right-handed • Native English speakers

12. 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

13. 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

14. Methods…Experimental Design: • Three presentation rates • Slow: 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

15. 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

16. 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)

17. Imaging Procedures: • Thermoplastic mask • 1.5 Tesla scanner • In 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

18. 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 movement • Inspection of these data revealed very few displacements greater than 0.5 mm in any direction, even for OVERT conditions

19. Analysis: Generation of Activation Images. • 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)

20. Analysis: Generation of Activation Images. • Time series was cross-correlated with a three parameter gamma function • Peak percent signal change • Time to response onset • Time 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

21. 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

22. 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

23. Analysis: Selection and Definition of Regions of Interest. • 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)

24. 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

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

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

27. Analysis: Regions-based Analysis. • 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)

28. 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 responding • Bilateral 6/44, anterior cingulate, SMA, bilateral primary motor cortex, bilateral cerebellum, bilateral thalamus

29. 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 flat for 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.

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

31. Comparisons were conducted for regions that showed a significant Time X Presentation Rate interaction • Interaction 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

32. 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

33. 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

34. Analysis: Analysis of Speech-related Movement and Noise. • 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)

35. Analysis I • 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

36. 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

37. Analysis II • 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

38. 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

39. 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

40. Analysis III • 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

41. 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

42. 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

43. 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 task • Usable images were obtained from only 5 of 11 subjects and images were usable only from the superior prefrontal cortex

44. 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

45. 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

46. In the present study, little movement-related artifact was observed (mainly in the low brain region) • Subjects moved their heads only minimally • Noise 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