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1.4. Alternative Techniques for Functional MRI during Speech

Fortunately the existence of a sizable delay between changes in the recorded BOLD-contrast local signal change and its antecedent neural activity allow experimental strategiesin which the auditory stimulus can be presented, or the speech response recorded, afterthe gradients have fallen silent. While usually said to limit temporal resolution in func-tional neuroimaging studies, it is the existence of hemodynamic delay and dispersion thatallow the interleaving of data acquisition and behavior, permitting task performanceunder relatively quiet experimental conditions with little acoustic interference. Becausethe hemodynamic response builds as the neuronal activity associated with task perform-ance continues, eight second task performance periods are sufficiently long to yieldexcellent single-subject activity maps. Many acquisition types are based on this lagbetween stimulus presentation or task performance and the associated hemodynamicresponse that is the source of the BOLD-contrast signal (Buckner et al., 1996; Kwonget al., 1992). The onset of the BOLD-contrast response occurs approximately 2–5 s after stimulus presentation, peaks around 5–6 s, and returns to baseline about 10–12 safter stimulus offset (Belliveau et al., 1991). Several approaches to data acquisition takeadvantage of the delay in BOLD-contrast response to avoid contaminating head motionand acoustic noise: clustered volume acquisition (Edmister, Talavage, Ledden, &Weisskoff, 1999), sparse temporal sampling (Hall et al., 1999), event-related (single-trial)designs (Birn et al., 1999; Huang et al., 2002), and the Behavior Interleaved Gradients(BIG) technique (Eden, Joseph, Brown, Brown, & Zeffiro, 1999). All of these techniquesemploy temporal separation of task performance and image acquisition and rely on thefact that the neural activity evoked by acoustic gradient noise is separable from thatrelated to perception of the intended stimulus (Talavage, Edmister, Ledden, & Weisskoff,1999). On the other hand, these methods also have their drawbacks. The primary disad-vantage being that, when compared to the more conventional continuous acquisitionmethods, fewer images are acquired per unit time, which, all other conditions beingequal, means reduced statistical power.

Recently, Birn et al. (2004) systematically examined how acquisition of functionalimaging data can be optimized by taking into account the temporal delay between theimmediate motion-induced signal change and the more slowly generated hemodynamicsignal change. Results from their simulations and experiments involving reading alouddemonstrate some advantages in discarding the images acquired during speech in brainregions prone to exhibit the effects of jaw motion artifact. However, removing segmentsof the time series in this way also results in an overall decrease in detection sensitivityover the entire brain volume, so the respective contributions of these competing effectsmust be kept in mind when selecting the details of the analysis procedure.

A different approach involves acquisition techniques in which task performance andimage acquisition are interleaved in time. In order to mitigate the effects of gradientnoise, these techniques employ an approach in which the gradients are switched off dur-ing periods of task execution and then immediately switched back on to allow samplingof the resulting hemodynamic activity. Detection of the task-related signal change relies

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on the presence of a neurovascular coupling lag of 4–8 s between stimulus onset andthe resulting BOLD-contrast response. In response to neuronal activity, there is an increase of blood flow and oxygen delivery (Kwong et al., 1992; Ogawa et al., 1992).Because the oxygen utilization increase is far less than the blood flow increase in rela-tion to neural activity, there is a net deoxyhemoglobin decrease, resulting in a decreasein local spin dephasing and therefore an increase in the MRI signal, the BOLD-contrastresponse. However, this signal modulation is shifted in time by 4–8 s, with the MRIsignal modulation exhibiting both delay and dispersion relative to its antecedent neural activity. These effects result in a loss of temporal information in the resultingmeasurements. However, because the general time of the delay is known, it is possibleto use this information to capture the resulting BOLD signal excursion in a specifictemporal interval.

Interleaved acquisition is a member of the larger class of evoked hemodynamicresponse techniques, also referred to as event-related fMRI techniques, that combine relatively brief stimulus presentation or task performance times with sufficient tempo-ral sampling to capture the shape of the evoked hemodynamic response. In comparisonwith other event-related approaches, the interleaved techniques tend to employ longerrepetition times (TR), allowing maximal longitudinal relaxation and therefore providinggreater MRI signal contrast and potentially greater sensitivity to small task-related sig-nal changes. While conventional methods of fMRI data acquisition data usually operatecontinuously, in the interleaved techniques the gradients are off during periods of taskexecution and subsequently activated to acquire data after the task interval has com-pleted. These interleaved techniques utilize the same basic pulse sequence parametersas those used in conventional continuous fMRI acquisitions, differing only in the addi-tion of a 9–12 s gap between the onsets of successive acquisitions. By interleaving task

CHAPTER 5. FUNCTIONAL NEUROIMAGING OF SPEECH PRODUCTION 135

w = real words p = pseudowords+ = fixation

TR=12 s

w p w p

4.05 0.2

Experimental Run (12 min):

Epoch:

2.45

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bird + plan + sun + +

scan

scan

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Figure 3. Timing diagram of an interleaved data acquistion experiment.



performance and data acquisition, the interleaved techniques allow the subject to per-form the tasks under relatively quiet experimental conditions. The details of the eventtiming are shown in Figure 3.

1.5. Advantages and Disadvantages of Interleaved Acquisition Techniques

Acoustic gradient noise during task performance causes measurable BOLD-contrastsignal modulations in both cortical and subcortical structures (Bandettini et al., 1998). Inconventional continuous data acquisition procedures, the gradient noise occurs equally inthe control and task conditions. Assuming that the signal changes due to gradient noiseare linearly additive with other sources of signal change (e.g. task-related changes), inprinciple it should be possible to subtract the noise effects. In this way categorical dataanalysis approaches based on image subtraction, such as Student’s t-test, can be used toidentify regions that exhibit task-related activity. Although it is reasonable to assume thatlinear additivity for gradient noise might hold for many cortical regions, it is less likelythat this assumption is reasonable for cortical areas known to be responsive to auditorystimuli (Talavage & Edmister, 2004). Non-linear effects and interference are particularlyto be expected at frequencies near those generated by the gradients.

By employing a longer TR than customarily used in conventional continuous imaging,interleaved acquisition techniques have potential increased sensitivity to small signalchanges, resulting from the improved contrast-to-noise that occurs with longer TR inter-vals as a result of more fully recovered longitudinal relaxation. However, the loss of sig-nal due to incomplete recovery of the longitudinal magnetization with shorter TRs hasbeen shown to be outweighed by the increased statistical power gained by the larger num-ber of samples collected in that situation (Constable & Spencer, 2001).

When using interleaved approaches, the proportion of time spent in performance of thetarget task is reduced, resulting in a situation in which the subject makes relatively fewerresponses during the imaging session than during a continuous acquisition experimentutilizing the same overall run length. Therefore, interleaved techniques may be less sen-sitive because of the smaller number of samples collected in the same acquisition period.However, the reduced power related to the smaller sample size may be balanced by thefact that, when using interleaved gradients, the subjects alternate more frequentlybetween target and control tasks, with an attendant reduction in response habituation andtherefore greater task-related signal modulation.

Also with interleaved acquisition techniques, susceptibility artifacts resulting from jawand tongue motion can be greatly reduced. Experiments involving verbal responses arenecessarily associated with orofacial movement that can induce significant susceptibilityartifacts in medial temporal and orbitofrontal cortical regions. As these areas are involvedin language production and understanding, it is obvious that tasks involving orofacialmovement could be associated with signal drop-out or image distortion in the veryregions that would be the principal objects of study. Speech is also likely to be associated



with periodic head motion, resulting from the mechanical coupling of the jaw and skullsuch that relatively small jaw movements can result in large rotational movements of theskull. Since even small amounts of uncorrected interscan motion can result in both false-positive and false-negative effects in statistical maps, even when using interleavedtechniques it is advisable to take precautions to minimize head motion using comfortablerestraints that allow unfettered jaw motion.

To illustrate the application of this method, Figure 4 shows an example of interleavedacquisition used to detect activity related to single word reading. An interleaved designwas used to reduce the problem of susceptibility artifacts resulting from head and jawmovements. This is an important issue in understanding the brain mechanisms responsi-ble for language processing, because evidence from PET studies, that are uncontaminatedby motion related susceptibility artifacts, indicates that covert and overt namingresponses engage different neural processing systems (Bookheimer et al., 1995). Resultsfrom a single subject are shown for the comparison of reading words silently versus fix-ation (bottom) and reading words aloud versus fixation (top).

Figure 4. Interleaved and continuous acquisition compared.


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Table 1 fMRI studies employing speech responses.

Continuous Block vs. vs.

Reference Speech task event-related interleaved Comments

Abrahams et al. Verbal fluency, Block Interleaved(2003) confrontation naming

Abrahams et al. Verbal fluency, Block Interleaved(2004) confrontation naming

Aldenkamp et al. Naming task Block Interleaved(2003)

Baciu, Rubin, Word fluency Block Continuous Soft articulation requested;Decorps, and comparison of aloud and silentSegebarth (1999) word fluency

Barch et al. Stroop task, verb Block Continuous Avoid scanning at throat and (1999) generation, noun mouth, discard data acquired

reading during speech; comparison ofaloud and silent Stroop task and noun reading

Barch Brover, Sabb, Verb generation Event-related Continuousand Noll (2000)

Barrett, Pike, and Paus (2004) Reading before and Event-related Interleavedafter mood induction

Birn, Bandettini, Cox, and Speech production Block and ContinuousShaker (1999) event-related


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Birn, Cox, and Bandettini (2004) Word reading Block and Continuous Discard images acquired event-related during speech

Burgund, Lugar, Miezin, Object naming Event-related Continuousand Peterson (2003)

Burton, Noll, Word repetition Block Continuousand Small (2001)

de Zubicaray, Wilson, Picture-word task Event-related InterleavedMcMahon, and Muthiah (2001)

de Zubicaray, McMahon, Picture-word task Event-related InterleavedEastburn, and Wilson (2002)

Dietz, Jones, Gareau, Word reading Block Interleaved Comparison of aloud and silentZeffiro, and Eden (2005) word reading

Dietz, Jones, Word reading Block Interleaved and Comparison of aloud and silentTwomey, Zeffro, continuous word readingand Eden, (in press)

Eden et al. (2004) Word reading Block Interleaved

Frenck-Mestre, Word and sentence Block ContinuousAnton, Roth, Vaid, readingand Viallet (2005)

Grabowski et al. Object naming Event-related Continuous Adaptive pacing(2006) algorithm

Haller, Radue, Sentence generation, Event-related ContinuousErb, Grodd, and word and sentence Kircher (2005) reading

Hashimoto and Sentence reading Block InterleavedSakai (2003)

(Continued)


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Table 1(Continued)



He et al. (2003) Chinese word and Block Continuous Comparison of aloud and silentpinyin reading Chinese word and pinyin reading

Heim, Opitz, and Picture naming, Event-related ContinuousFriederici (2002) grammatical gender

Huang, Carr, and Cao Letter naming, animal Event-related Continuous Comparison of aloud and silent(2002) name generation letter naming and animal

name generation

Jung, Prasad, Qin and Name repetition Event-related Continuous Active noise cancellationAnderson (2005) (in new order)

Kan & Thompson- Picture naming Block Interleaved Comparison of aloud andSchill (2004) silent picture naming

Kemeny et al. (2006) Sentence generation Block Continuous

Kemeny,Ye, Birn, and Object and action naming Event-related ContinuousBraun (2005)

Kircher, Brammer, Levelt, Continuous speech Event-related ContinuousBartels, and McGuire (2004) production

Leger et al. Picture naming and Block Continuous(2002) picture/word rhyming


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Liegeois et al. Verb generation, Block Interleaved Comparison of aloud and silent (2003) word repetition verb generation

Martin et al. (2005) Picture naming Block Continuous

McCarthy, Blamire, Word generation, Block Continuous Comparison of aloud and silent Rothman, Gruetter, word repetition word generationand Shulman (1993)

Naeser et al. (2004) Speech production Block Continuous Dynamic susceptibility contrast fMRI technique

Nelles et al. (2003) Read and Event-related Continuousgenerate words

Neumann et al. (2003) Sentence reading Event-related Continuous

Neumann et al. (2005) Sentence reading Event-related Continuous

Owen, Borowsky, Word naming Block Continuousand Sarty (2004)

Palmer et al. Word stem Event-related Continuous Comparison of aloud and silent (2001) completion word stem completion

Peck et al. (2004) Word generation Event-related Continuous

Phelps, Hyder, Blamirc, Word repetition, antonym Block Continuousand Shulman (1997) generation, word generation

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Table 1(Continued)



Preibisch et al. (2003a) Sentence reading Event-related Continuous

Preibisch et al. (2003b) Word and sentence reading Event-related Continuous

Riecker, Ackermann, Speech and melody Event-related Continuous Comparison of aloud and silentWildgruber, Dogil, and production speech and melody productionGrodd (2000)

Rosen, Ojemann, Oilinger, Word stem completion Event-related Continuous Comparison of aloud and silent and Petersen (2000) word stem completion

Shuster and Word reading Event-related Continuous Comparison of aloud and silent Lemieux (2005) word reading

Small et al. (1996) Word reading Block Continuous

Turkeltaub, Eden, Jones, Word reading Block Interleavedand Zeffiro (2002)

Viswanath, Karmonik, King, Speech production Event-related ContinuousRosenfield, and Mawad (2003)

Yetkin et al. Word generation Block Continuous Comparison of aloud and silent (1995) word generation



With the interleaved acquisition mechanism, jaw movement does not occur during dataacquisition, resulting in reduced signal drop-out and geometric distortion effects in thederived statistical maps. The data show that reading aloud and reading silently make dif-ferent demands on the inferior frontal gyrus (IFG).

Because of their lengthy TR intervals, interleaved techniques have limited temporalresolution and are optimal for experimental designs requiring imaging of the entire brainat the relatively low sampling rates of six times per minute or less. Two to four secondsare required to image the entire brain utilizing echo-planar imaging. As the hemodynamicresponse to a brief movement takes ten seconds to complete, it is possible to image theentire cerebrum during the peak of the hemodynamic modulation.

Because of their relative insensitivity to acoustic and motion artifacts, the interleavedtechniques produce activity maps that are comparable to or better than those derivedusing continuous acquisition, possibly because the reduced inter-scan head motion wouldresult in less temporal image misregistration and therefore higher resulting levels of statistical significance. In addition, interleaved techniques employ a longer TR that can result in increased sensitivity to small signal changes due to the improved contrast-to-noise. In Table 1 we present a guide to some of the recent fMRI work using speechresponses to study the neural mechanisms of cognitive processing. Both continuous andinterleaved techniques are employed using both block and event-related timing arrange-ments.

1.6. Summary of Recommendations

The proscription against the use of speech responses in functional MRI experiments isnot warranted, even though jaw motion can be associated with dramatic artifacts instatistical maps. The use of event-related and interleaved data acquisition techniques cangreatly reduce the effects of acoustic gradient noise on detection and estimation of spatialand temporal patterns of task-related activity. Very soon, improvements in MR imagingequipment will include both better acoustic isolation of the subject and active noise-cancellation capabilities, allowing ecologically valid communication studies in muchquieter experimental environments.

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