1. Age Group Comparisons in Category Member Generation Tasks: Effect of Stimulus Design Age Group Comparisons in Category Member Generation Tasks: Effect of Stimulus Design Keith M. McGregor 1,3, Michelle L. Benjamin 1,2, Yu-Ling Chang 1,2, Zvinka Zlatar 1,2, Colin Rackelman 1,2,4, Megan Gaiefsky 1,2, Ilana Levy 1,2, Keith D. White 1,3,4, and Bruce Crosson 1,2,4 Department of Veterans Affairs Rehabilitation Research and Development Brain Rehabilitation Research Center at the Malcom Randall VA Medical Center 1 University of Florida Departments of Clinical and Health Psychology 2, and Psychology 3,and McKnight Brain Institute 4, Gainesville, Florida Presented at the February 2008 International Neuropsychological Society Conference, Waikoloa, Hawaii This poster is available on the Web at http://www.BIRC.phhp.ufl.edu Acknowledging methodological differences in response production (i.e. – overt versus covert), the data indicate that block paradigms with covert response may provide greater sensitivity to lateral frontal and basal ganglia activation in healthy adults during category member generation tasks. However, event-related FMRI paradigms will continue to have relevance in studying certain patient populations in which on-line task performance needs to be carefully monitored (e.g., language production in nonfluent aphasia; Crosson et al, 2007). On-line task performance may be beneficial for neurologically normal populations, since different subsets of healthy individuals may show different patterns of neural activation to complete a task. E.g., Wierenga et al (2007): “high- functioning” old subjects showed a positive correlation between naming accuracy and right inferior frontal cortex (IFC), whereas “low-functioning” old subjects and young subjects showed a negative correction in right IFC; all groups showed positive correlations between accuracy and left IFC activity. Additionally, overt response monitoring within an event-related imaging paradigm may provide fruitful secondary analysis strategies for a better understanding of language functions’ complex interactions and delineated task-related contributions of specific brain areas (e.g., correct vs. error response comparisons). (Meinzer et al., 2006) INTRODUCTION METHODS CONCLUSIONS RESULTS REFERENCES Acknowledgements of support: VA RR&D Center of Excellence Grant #F2182C and Research Career Scientist Award (Crosson); McKnight Brain Institute of University of Florida E. F. McKnight Grants. Subjects: Twenty-two neurologically normal older adults at least 65 years of age and 22 young adults between 18-35 years of age were recruited from the community and participated in two fMRI category exemplar tasks (BLOCK & EVENT). Older subjects were given a short mental status screening (MMSE) to screen for possible dementia and Mild Cognitive Impairment; all older subjects scored > 27 on the MMSE. See Table 1 for descriptive demographics. Table 1. Group Demographics fMRI Experimental Procedures: Baseline visual fixation task with simultaneous audio and visual presentation of category exemplars and stop cue during active trials in both fMRI paradigms. 60 total categories presented only once across BLOCK and EVENT conditions. EVENT Condition: Overt, single-item response, event-related fMRI of category-member generation for 44 categories across 4 fMRI runs (e.g., “eagle” for “birds”). 3.4 seconds/category for each active exemplar generation event. Resting blocks of 15.3, 17, 18.7, and 20.4 secs between active trials. BLOCK Condition: Covert, multiple-response, block paradigm fMRI of category-member generation for 16 total categories across 2 fMRI runs. 17 seconds/category for each active exemplar generation block. Resting blocks of 10.2, 11.9, and 15.3 seconds between active blocks. fMRI Acquisition: 3 T Siemens Allegra instrument, gradient echo planar images. Functional images: 240mm FOV, 64x64 matrix, 3.8mm x 3.8mm in-plane resolution, TR=1700 ms, TE=25 ms, flip angle=70 °. Whole-brain slice coverage using 32 5mm thick slices (BLOCK=axial acquisition ; EVENT=sagittal acqusition). High-resolution T1-weighted 3D MP-RAGE axial scan (TE = 4.13 ms; TR = 2000 ms; FOV = 240 mm; FA = 8 ° ; matrix size = 256x192; 128 1.3mm slices). fMRI Analyses: AFNI FWHM spatial-smoothing at 4mm. 3dDeconvolve: Deconvolution analysis with response estimate (maxlag) of: EVENT: 12 images omitting the first two responses (minlag) BLOCK: 20 images Optimal stimulus presentation paradigms in functional magnetic resonance imaging (fMRI) continues to be vital to experimental design particularly in the study of language processes. Category member generation tasks have indicated a relationship between activation between lateral inferior and medial frontal areas and the basal ganglia (Crosson et al., 2003; Crosson et al., 2005), a finding with particular relevance to the imaging studies of aging and stroke rehabilitation. The imaging of such word generation tasks for between group comparisons has been reported using both block (Crosson et al., 2003) and event-related paradigms (Crosson et al., 2005; Wierenga 2007), but we are not aware of research comparing the sensitivity of different paradigm designs on group activation comparisons, particularly in inferior frontal and subcortical areas. The present study compares age related differences in activation across event related and block design fMRI during word retrieval (category member generation) tasks. Subject Group (age range) Mean Age (SD) Sex (F:M) Years Education Mean (SD) MMSE total Mean (SD) OLD71.3 (6.2)9:1316.3 (3.2)29.4 (0.9) YOUNG25.5 (4.5)12:1016.4 (2.3)---- Block Event-related L RL R Age Group Comparison Word Generation Comparison to Baseline LeftRight Inferior Frontal Gyrus (BA 47/11)Dorsal Medial Thalamus Precentral Sulcus (BA 6)Anterior Thalamus Precentral Gyrus (BA 4)Putamen Middle Frontal Gyrus (BA 10) Middle Frontal Gyrus (BA 47/11)Supramarginal Gyrus (BA 40) Capular projection of striatumAngular Gyrus (BA 39) Anterior Thalamus LeftRight Superior Temporal Gyrus (BA 42)Superior Parietal Lobule (BA 7) Lingual/Fusiform Area (BA 19/37)Lingual Gyrus (BA 19) CerebellumPrecentral gyrus (BA 4) Anterior Thalamus Talairach montage of task-to- baseline activation comparisons: conjunction analysis of Age at Block (top) and Event- related (bottom) comparisons @ p<.0001: Blue indicates Older activation; Yellow indicates Younger activation; Green indicates Both Older and Younger activation L R L R Block Event- related Crosson, B., Benefield, H., Cato, M. A., Sadek, J. R., Moore, A. B., Wierenga, C. E., Gopinath, K., Soltysik, D., Bauer, R. M., Auerbach, E. J., Gokcay, D., Leonard, C. M., & Briggs, R. W. (2003). Left and right basal ganglia and frontal activity during language generation: Contributions to lexical, semantic, and phonological processes. Journal of the International Neuropsychological Society, 9, 1061-1077. Crosson B, Moore AB, Gopinath K, White KD, Wierenga CE, Gaiefsky ME, Fabrizio KS, Peck KK, Soltysik D, Milsted C, Briggs RW, Conway TW, Gonzalez Rothi LJ.(2005) Role of the right and left hemispheres in recovery of function during treatment of intention in aphasia. J Cogn Neurosci. 17(3):392-406. Crosson,B, McGregor, K. Gopinath. K. Conway. T,. Benjamin, M, Chang, YL, Moore, A.B., Raymer, A.,. Briggs, RW., Sherod, M., Wierenga, C and. White, KD. (2007) "Functional MRI of Language in Aphasia: A Review" Neuropsychol. Rev., 17:157-177, 2007 Meinzer, M., Flaisch, T., Obleser, J., Assadollahi, R., Djundja, D., Barthel, G., & Rockstroh, B. (2006). Brain regions essential for improved lexical access in an aged aphasic patient: a case report. BMC Neurology, 6, 1-10 Wierenga, C. E., Benjamin, M., Gopinath, K., Perlstein, W. M., Leonard, C. M., Rothi, L. G., Conway, T., Cato, M. A., Briggs, R., & Crosson, B. (2007). Age-related changes in word retrieval: Role of bilateral frontal and subcortical networks. Neurobiology of Aging,. Talairach montage showing group activation comparisons @ p Younger; Orange indicates Younger > Older