The outcome of fmri language mapping is affected by patient fatigue

Transcription

1 The outcome of fmri language mapping is affected by patient fatigue Poster No.: C-2314 Congress: ECR 2016 Type: Scientific Exhibit Authors: M. Kiss, G. Rudas, L. R. Kozak; Budapest/HU Keywords: Neuroradiology brain, CNS, MR-Functional imaging, MR, Outcomes analysis, Image verification DOI: /ecr2016/C-2314 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 22

2 Aims and objectives Mapping the eloquent areas and/or determining language lateralization is very important for presurgical mapping, hence mapping the language/speech network is one of the most important usage of clinical functional MRI (fmri) [1-3]. Choosing the optimal paradigm is challenging because of the variability in activation among different paradigms, the differential contribution of cognitive processes to the resulting activations and the difficulties of monitoring patient performance [4, 5]. There are several fmri paradigms for mapping the eloquent areas [1-3], and it is important to underline that none of these methods yield results exclusive for language related areas as there are other cognitive processes involved in their execution, i.e. attention, decision-making, working memory, and fatigue. Most of the applied paradigms are designed to require a steady level of attention throughout the imaging session, however lapses of attention and fatigue may still influence the outcome and the activation patterns [4]. In this study we aimed to investigate the possible effects of fatigue and/or loss of interest during long acquisition times in four [1, 3] fmri language mapping paradigms. Based on our previous experience we expected paradigm-dependent differences in the resulting activation maps [1-5]. Moreover, we hypothesized that there will be differences between the activation patterns obtained from the first-, and the second half; indeed we expected smaller extent of task-specific activations and an increased activation of the default mode network (DMN) for the second half of the data acquisition due to the fatigue and/or loss in interest during stimulus presentation [6, 7]. Methods and materials Participants Nineteen healthy volunteers participated in the experiment (14 females). None of them suffered from psychiatric or neurological disorders and they have never suffered head injury. We had to exclude two participants' data due to claustrophobic attack during data acquisition, hence the analysis includes data of 17 participants (14 females). Data acquisition Structural and functional data were collected with a 3T MRI scanner, with 8-channel head coil. For BOLD-fMRI, T2* weighted echoplanar images were acquired with 3 mm isotropic voxels (80x80 image matrix, with a field of view (FOV) of 240x240 mm, TR: 3000 ms). During the fmri experiment visual stimuli were projected onto a translucent screen located at the back of the scanner before using a DLP projector at a refresh rate of 75 Page 2 of 22

3 Hz. A high resolution 3D volumetric T1 weighted turbo field echo series (1x1x1 mm, 180 consecutive slices, without gap) was also acquired for each participant for anatomical reference. fmri paradigms The experiments consisted of 4 language mapping paradigms (Fig 1.). Each of them was block-design with 12 active and 12 passive 24-second-long blocks (192 volumes), with odd numbered blocks providing the language/speech tasks and even numbered blocks providing the baseline conditions [1, 3]. Fig. 1: Fig 1. Schematic representation of the fmri language paradigms Picture Naming: active condition (24s): covert naming of images presented in every 3s, and decision whether the image shows a living entity or an object; baseline condition Page 3 of 22

4 (24s): Fourier-scrambled version of images are shown, the patient is instructed to rest, but mark the direction of arrows overlaid on the images. Synonym task: active condition (24s): synonym decision making on word pairs; baseline condition (24s): similarity decision making on 5-letter consonant string pairs. Speech comprehension: active condition (24s): listening to pre-recorded speech; baseline condition (24s): listening to pre-recorded reverse speech. Sentence generation: active condition (24s): sentence generation based on presented words; baseline condition (24s): fixation baseline. Data processing Off-line data analysis was performed using Statistical Parametric Mapping (Version 8) software (SPM8, Wellcome Department of Cognitive Neurology, London, UK), with MATLAB 2013a (The MathWorks Inc., Natick, MA). We applied the standard SPM's pipeline: realignment, coregistration (between the mean functional and the structural volume), spatial segmentation (of the structural volume) with normalization (of the structural and functional volumes) to MNI space, and smoothing with a 6 mm full-with half-maximum Gaussian Kernel. Data/Statistical analysis Statistical parametric maps of task-related activations were calculated using the general linear model (GLM) approach, applying SPM's canonical hemodynamic response function (HRF) without spatial or temporal derivatives. Head movements during data acquisition were also included in the model as nuisance regressors, and we applied an AR(1) autocorrelation model for the analysis. In an additional step we performed functional connectivity analysis using the CONN functional connectivity toolbox (15.a). In addition to the above described preprocessing, automated artifact detection and censoring was applied using the artifact detection tool (ART). For building the functional connectivity model the mean signal of the white matter and CSF compartment and the task/rest effect covariates were regressed out of the data, and the resulting BOLD signal was also passed through a temporal high-pass filter at Hz. Functional connectivity was measured between predefined atlas ROIs by calculating Fisher r-to-z transformed between ROI correlation coefficients, and then applying parametric statistics (ANCOVA model) on the resulting Gaussianized correlation matrices. Page 4 of 22

5 For both analysis methods we compared the first and second halves of each run to investigate the effects of fatigue, both on the single subject and on the group level using parametric statistics (one sample t-test and paired t-test). Images for this section: Fig. 1: Fig 1. Schematic representation of the fmri language paradigms Page 5 of 22

6 Results Basically, for simple activation mapping (group statistics with one sample t-test) all paradigms yielded the expected task activations [3], both for the first and second half of the experiment, but there were some prominent differences between the first and second halves' results involving the DMN and the parietal attention networks [6, 7]. Group-level activation in the first and second halves of the experiment paradigms To assess overall activation maps in the first and second halves of each paradigm run on the group level, we applied second-level one sample t-test for the first-level activations contrast obtained on the first and second halves of each experimental run analyzed in separate GLMs. Picture Naming We found visual activations both in the first and second half of the acquisition (Fig 2.), which was expected given the visual stimulation, and the relatively stable level of attention required for identifying the pictures. We also managed to identify task-relevant activations in the Broca's area (left inferior frontal gyrus), both in the first and second halves of the task. Fig. 2: Fig 2. Picture Naming paradigm results. Both relevant activations have bigger extent in the second half of the experiment. First Part-red, Second Part-blue, Both Parts-purple. Synonym task There was a prominent change in activation patterns between the two halves (Fig 3.). We could only map Broca's region in the first half of the scanning session, while Wernicke's Page 6 of 22

7 area in the left temporo-parietal region was present in both halves of the session. Widespread activations involving the hippocampi bilaterally, and the right temporoparietal regions and right insula were observed only for the second half. Fig. 3: Fig 3. Synonym paradigm results. Activation pattern changes between the first and second half. The Broca's region was activated in the first part of the experiment, but some Wernicke activations were present during the whole session. First Part-red, Second Part-blue, Both Parts-purple. Speech comprehension Significant activations appeared during the whole scan regarding to the primary auditory cortex and Wernicke's area (Fig 4.). These activations had bigger extension in the second half. Fig. 4: Fig 4. Speech paradigm results. Activations have bigger extent in the second half. The primary auditory cortex and Wernicke's were activated the whole experiment. First Part-red, Second Part-blue, Both Parts-purple. Auditory Decision Page 7 of 22

8 Activations were present with bigger extent in the first halves of the scan (Fig 5.). Broca's area was activated in the first half, but Wernicke activations appeared during the whole measurement. Fig. 5: Fig 5. Auditory decision paradigm results. The Broca activation is more prominent in the first part, albeit the Wernicke was activated during the whole scan. First Part-red, Second Part-blue, Both Parts-purple. As we seen we found different activation maps depending on the paradigms used, and we found differential activation in the Broca and Wernicke areas, with Broca's region appearing predominantly in the first halves of the paradigm session, while Wernicke's area activation during the whole session for at least three paradigms. Group-level activation differences between the first and second halves of the experimental paradigms To assess differences between the activation maps obtained on the first and second halves of each paradigm run we applied second-level paired t-tests comparing the firstlevel activation contrasts obtained on the first and second halves of each experimental run. For this analysis we hypothesized that language related areas may have more dominant activations in the first half of the paradigm runs and DMN may show more significant activation in the second parts, because of the participants' fatigue, decrease of attention or boredom. Picture naming Language related and visual areas were more active in the first half compared to the second half, while the DMN was more active in the second half of the paradigm run (Fig. 6.). This shift of relative activations towards the DMN is consistent with some loss of attention during the second half of the task. Page 8 of 22

9 Fig. 6: Fig 6. Picture Naming paired t-test results. Direct comparison shows relatively higher activations in the language and visual areas in the first half, and relatively higher DMN activation in the second half. Higher relative activations in the first part(red) vs. second part(blue). Synonym paradigm Similar to the picture naming task, language areas were more active during the first halves, while the parietal attentional network had higher relative activations during the second half of the paradigm runs (Fig 7.). This might be due to the increased recruitment of the attention network needed to keep the level of attention steady for the whole run. Fig. 7: Fig 7. Synonym paired t-test results. We observer higher relative activations in the first halves, and higher relative activations in the bilateral attention networks Page 9 of 22

10 during the second halves. Higher relative activations in the first part(red) vs. second part(blue). Speech comprehension Similarly to the picture naming task language-related areas were more active in the first half compared to the second half, while the DMN was more active in the second half of the paradigm run (Fig. 8.). This shift of relative activations towards the DMN is consistent with some loss of attention during the second half of the task. Fig. 8: Fig 8. Speech comprehension paired t-test results. Higher relative activations are present in the first part, in the Broca-, and Wernicke areas, while the default mode network has higher relative activation during the second half. Higher relative activations in the first part(red) vs. second part(blue). Auditory Decision Similarly to the picture naming and the speech comprehension tasks language-related areas were more active in the first half compared to the second half, while the DMN was more active in the second half of the paradigm run (Fig. 9.). This shift of relative activations towards the DMN is also consistent with some loss of attention during the second half of the task. Page 10 of 22

11 Fig. 9: Fig 9. Auditory decision paired t-test results. Higher relative activations are present in the first part in the Broca-, and Wernicke areas, while the default mode network has higher relative activations during the second half. Higher relative activations in the first Part(red) vs. second Part(blue). Task related connectivity analysis In a separate step we did whole brain functional connectivity analysis to describe fatigueinduced changes in task-related functional connectivity. Here we present results focusing on the ventromedial prefrontal cortex and the orbitofrontal cortex, because these two areas play major role in decision making and reward processing. The analysis strategy is similar: we investigated task-related connectivity in the first and the second halves of the paradigm runs in separate connectivity models, hence these results are related to the first set of results presented in this poster, i.e. the group-level activations in the first and second halves of the experimental paradigms. The following trends are shown in Figures Both in the picture naming, speech comprehension and auditory decision task: there is an increase in the number of significant connections in the second halves of the paradigm runs, with prominent connectivity between the medial prefrontal areas and the supramarginal gyrus. This change of task-related connectivity is not present for the speech comprehension task. The speech comprehension task is the only task in our panel that does not require decision masking during task performance. Therefore this observation of ventromedial prefrontal connectivity changes may be consistent with the possible recruitment of additional cortical areas for providing similar task performance over the whole paradigm runs. Page 11 of 22

12 Fig. 10: Fig. 10. Auditory decision paradigm functional connectivity analysis. Increased connectivity of the ventromedial prefrontal cortex in the second halves of the paradigm runs may represent recruitment of additional cortical areas for providing stable task performance. Fig. 11: Fig. 11. Picture naming paradigm functional connectivity analysis. Increased connectivity of the ventromedial prefrontal cortex in the second halves of the paradigm runs may represent recruitment of additional cortical areas for providing stable task performance. Page 12 of 22

13 Fig. 12: Fig. 12. Synonym paradigm functional connectivity analysis. Increased connectivity of the ventromedial prefrontal cortex in the second halves of the paradigm runs may represent recruitment of additional cortical areas for providing stable task performance. Page 13 of 22

14 Fig. 13: Fig. 13. Speech comprehension paradigm functional connectivity analysis. This is the only paradigm in our panel that does not involve decision making, this may explain the different pattern of connectivity compared to the other tasks. Images for this section: Fig. 2: Fig 2. Picture Naming paradigm results. Both relevant activations have bigger extent in the second half of the experiment. First Part-red, Second Part-blue, Both Partspurple. Fig. 3: Fig 3. Synonym paradigm results. Activation pattern changes between the first and second half. The Broca's region was activated in the first part of the experiment, but some Wernicke activations were present during the whole session. First Part-red, Second Part-blue, Both Parts-purple. Page 14 of 22

15 Fig. 4: Fig 4. Speech paradigm results. Activations have bigger extent in the second half. The primary auditory cortex and Wernicke's were activated the whole experiment. First Part-red, Second Part-blue, Both Parts-purple. Fig. 5: Fig 5. Auditory decision paradigm results. The Broca activation is more prominent in the first part, albeit the Wernicke was activated during the whole scan. First Part-red, Second Part-blue, Both Parts-purple. Fig. 6: Fig 6. Picture Naming paired t-test results. Direct comparison shows relatively higher activations in the language and visual areas in the first half, and relatively higher Page 15 of 22

16 DMN activation in the second half. Higher relative activations in the first part(red) vs. second part(blue). Fig. 7: Fig 7. Synonym paired t-test results. We observer higher relative activations in the first halves, and higher relative activations in the bilateral attention networks during the second halves. Higher relative activations in the first part(red) vs. second part(blue). Fig. 8: Fig 8. Speech comprehension paired t-test results. Higher relative activations are present in the first part, in the Broca-, and Wernicke areas, while the default mode network has higher relative activation during the second half. Higher relative activations in the first part(red) vs. second part(blue). Page 16 of 22

17 Fig. 9: Fig 9. Auditory decision paired t-test results. Higher relative activations are present in the first part in the Broca-, and Wernicke areas, while the default mode network has higher relative activations during the second half. Higher relative activations in the first Part(red) vs. second Part(blue). Fig. 10: Fig. 10. Auditory decision paradigm functional connectivity analysis. Increased connectivity of the ventromedial prefrontal cortex in the second halves of the paradigm runs may represent recruitment of additional cortical areas for providing stable task performance. Page 17 of 22

18 Fig. 11: Fig. 11. Picture naming paradigm functional connectivity analysis. Increased connectivity of the ventromedial prefrontal cortex in the second halves of the paradigm runs may represent recruitment of additional cortical areas for providing stable task performance. Fig. 12: Fig. 12. Synonym paradigm functional connectivity analysis. Increased connectivity of the ventromedial prefrontal cortex in the second halves of the paradigm runs may represent recruitment of additional cortical areas for providing stable task performance. Page 18 of 22

19 Fig. 13: Fig. 13. Speech comprehension paradigm functional connectivity analysis. This is the only paradigm in our panel that does not involve decision making, this may explain the different pattern of connectivity compared to the other tasks. Page 19 of 22

20 Conclusion Based on our previous experience we expected paradigm-dependent differences in the resulting activation maps [1-5], and we found the expected differences. Moreover, we hypothesized that there will be differences between the activation patterns obtained from the first-, and the second half; indeed we expected smaller extent of taskspecific activations and an increased activation of the DMN for the second half of the data acquisition due to the fatigue and/or loss in interest during stimulus presentation [6, 7]. We found differences between the first and second halves of paradigm runs on the group levels that are consistent either with the effects of fatigue or decrease of attention/interest. Moreover we found activation patterns that may be consistent with the additional recruitment of cortical processing areas to provide stable attention and/or task performance during the mapping runs. The difference in the behavior of the Broca and Wernicke areas is visible on the standard activation maps (Fig. 2-5.) except for the picture naming task, i.e. Broca activation are much less prominent or non-observable on the maps obtained from the second halves of the paradigms, while Wernicke activations are present throughout the paradigm runs. This difference may point out differential attentional modulation of the two areas, or different sensitivity to fatigue/boredom, but determining the underlying cause requires further investigative efforts. The relative activation maps show that language areas have higher relative activations during the first halves of the experiment, while the DMN (for picture naming, speech comprehension and auditory decision) and the parietal attentional networks (for the synonym task) have higher relative activations for the second halves of the paradigm runs. This observation is consistent with possible loss of attention and/or daydreaming during performing the task (for picture naming, speech comprehension and auditory decision) and a possible recruitment of additional attentional areas for steady task performance in case of the synonym task. This difference may also suggest that the attentional demand of the picture naming, speech comprehension and auditory decision paradigms is relatively low compared to the synonym task, but determining attentional demand was not the goal of this study. Nevertheless we monitored task performance (except for the speech comprehension task) and it was above 80% in all participants for all runs. For the speech comprehension task all participants could correctly tell details of the story heard during task presentation when asked upon leaving the scanner. The connectivity analysis results presented here may show a separation between the attentional demand, and the cognitive processing involved in decision making as we see recruitment of additional cortical areas (especially supramarginal regions) in the second halves of the paradigm runs in cases where active decision making is part of the paradigms. Further functional connectivity results (not shown) yielded results consistent with the observations presented on the activation maps and relative activation maps. Page 20 of 22

21 The 9.6 minute session length may limit the power of our observation, i.e. fatigue- and boredom-related changes, or recruitment of additional processing power may be more prominent if the sessions are even longer. This could be considered as a limitation of our study, however we wanted to investigate effects on a timescale that is compatible with clinical fmri mapping. The prominence of these effects on such a short time-scale show a possible additional pitfall in fmri mapping that may require further investigation. Taken together, fatigue, boredom and/or decrease of attention may affect the outcome of fmri mapping even on relatively short time-scales, but this effect may possibly be dependent on the attentional demand of the mapping paradigm itself. Personal information L.R.K. was supported by the Bolyai Research Fellowship Program of the Hungarian Academy of Sciences, and by the Hungarian National Brain Research Program grant KTIA/NAP_ References 1. Kozak L.R., et al., [Functional magnetic resonance imaging for cortical mapping in epilepsy]. Ideggyogy Sz, (9-10): p Bookheimer, S., Pre-surgical language mapping with functional magnetic resosnance imaging. Neuropsychol Rev, (2): p Kozak, L.R., et al., Functional MRI for neurosurgical planning: retrospective analysis of our task panel with respect to language dominance. Neuroradiology, (Suppl 1): p. S Haller, S. and A.J. Bartsch, Pitfalls in FMRI. Eur Radiol, (11): p Zaca, D., S. Jarso, and J.J. Pillai, Role of semantic paradigms for optimization of language mapping in clinical FMRI studies. AJNR Am J Neuroradiol, (10): p Page 21 of 22

22 6. Fox, M.D., et al., The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A, (27): p Smith, S.M., et al., Correspondence of the brain's functional architecture during activation and rest. Proc Natl Acad Sci U S A, (31): p Page 22 of 22