Hemispheric Asymmetry Reductions in Older Adults during Category Exemplar Generation Michelle L. Benjamin1,2, Keith M. McGregor1,3, Yu-Ling Chang1,2, Keith D. White1,3,4, Colin Rackelman1,2,4, Megan Sherod 1,2, Ilana Levy 1,2, and Bruce Crosson 1,2,5 Department of Veterans Affairs Rehabilitation Research and Development Brain Rehabilitation Research Center at the Malcom Randall VA Medical Center1 University of Florida Departments of Clinical and Health Psychology2, and Psychology3,and McKnight Brain Institute4, 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 METHODS RESULTS ABSTRACT Subjects: Twenty-two older neurologically normal 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 a block design fMRI covert category exemplar generation task. 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 Objective: Old adults demonstrate frontal hemispheric asymmetry reduction during fMRI of picture naming compared to young adults (Wierenga et al., 2007); this finding results from increased right frontal activity for old adults. Although Wierenga et al. (2007) found small reductions in right basal ganglia activity in old persons, her event-related paradigm appeared less sensitive to basal ganglia differences. Block category exemplar generation has demonstrated sensitivity to left and right basal ganglia activity in young adults during word generation (Crosson et al., 2003). The current study examined the functional anatomy of aging and category exemplar generation with a block design during FMRI. Participants and Methods: Twenty-two old (>65 years old) and 22 young (18-35 years old ) participants completed a block fMRI paradigm, silently generating exemplars for 17 seconds/category for 16 categories. FMRI data was analyzed using AFNI 3dANOVA and subsequent t-tests (p<.005). Results: Old participants demonstrated greater functional activity than young adults in several cortical and subcortical areas. Left hemisphere differences included inferior frontal (BA47/11), precentral (BA6), sensorimotor (BA4, BA3/1/2) and medial frontal (BA6) cortices, as well as striatocapsular gray matter. Right hemisphere differences were found in middle frontal (BA10) and posterior perisylvian areas (supramarginal and angular gyri), as well as dorsomedial thalamus. Bilateral differences included the putamen, anterior thalamus, precuneus, and posterior cingulate. Conclusions: Compared to young adults, old adults exhibited greater activation for several cortical and subcortical areas, including regions implicated in intentional aspects of language. However, changes were distributed across the hemispheres rather than concentrated in one hemisphere. LEFT & RIGHT BASAL GANGLIA RIGHT THALAMUS Subject Group (age range) Mean Age (SD) Sex (F:M) Years Education Mean (SD) MMSE total OLD 71.3 (6.2) 9:13 16.3 (3.2) 29.4 (0.9) YOUNG 25.5 (4.5) 12:10 16.4 (2.3) ---- fMRI Experimental Procedures: Baseline visual fixation task with simultaneous audio and visual presentation of category exemplars and stop cue during active fMRI trials. Covert, multiple-response, block paradigm fMRI category exemplar generation (e.g., silent generation of “eagle, robin, cardinal…” for category “birds”). 16 total categories across 2 fMRI epi 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: 3T 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=70o. Axial acquisition whole-brain imaging using 32 5mm thick slices. High-resolution T1-weighted 3D MP-RAGE axial scan (TE = 4.13 ms; TR = 2000 ms; FOV = 240 mm; FA = 8o; matrix size = 256x192; 128 1.3mm slices). fMRI Analyses: FWHM spatial-smoothing at 4mm. AFNI 3dDeconvolution and 3dANOVA. RESULTS SUMMARY: Age-related functional activity differences were found in both hemispheres and in several brain regions for this task. Old participants demonstrated greater age-related functional activity than young adults in several cortical and subcortical areas: LEFT: inferior frontal (BA 47/11); precentral (BA6); sensorimotor (BA4, BA3/1/2); medial frontal (BA6); striatocapsular gray matter. RIGHT: middle frontal (BA10); supramarginal gyrus; angular gyrus; dorsomedial thalamus. BILATERAL: putamen; anterior thalamus; precuneus; posterior cingulate. Notably, young adults did not show any areas of greater activity as compared to old adults. INTRODUCTION HEMISPHERIC ASYMMETRY REDUCTION IN OLDER ADULTS (HAROLD): Compared to young adults, healthy old adults tend to recruit neural resources differently to complete tasks, showing an age-related hemispheric asymmetry reduction in neural recruitment. Cabeza (2002) coined this observation as hemispheric asymmetry reduction in older adults (HAROLD), summarizing findings on memory tasks of episodic and semantic retrieval, as well as working memory, perception, and inhibitory control within the HAROLD framework. Age-related neural recruitment differences appear to be task-dependent and can include either additional or reduced recruitment within the task-dominant hemisphere and associated neural regions as well as contralateral hemisphere activity increases. HAROLD & LANGUAGE FUNCTION: HAROLD functional imaging investigations within the context of language functions: Picture naming: old adults demonstrate frontal hemispheric asymmetry reductions compared to young adults, resulting from increased right frontal activity in old adults (Wierenga et al., 2007). Verb generation: Persson et al (2004) demonstrated differential recruitment in old (versus young) adults during verb generation for noun associates: less left inferior frontal, left inferior temporal, and anterior cingulate cortex greater activation in right inferior frontal cortex. CATEGORY EXEMPLAR GENERATION: FMRI word generation research by Crosson et al (2003) in young adults suggests: Left pre-SMA—dorsal caudate nucleus—ventral anterior thalamic loop activity during word generation. Right basal ganglia activity in the absence of right frontal activity indicative of right frontal suppression during word generation. CURRENT STUDY AIMS: Age-related differences in the neural network for word generation have not been evaluated. Thus, the current study aimed to examine functional imaging differences between young and old subjects during category exemplar generation using fMRI and a block paradigm covert word generation paradigm similar to that used in healthy young adults (Crosson et al, 2003). Increased right frontal activity was expected for old adults in this paradigm as an indicator of reduced right basal ganglia suppression of the language-nondominant right hemisphere during this task. CONCLUSIONS RESULTS Compared to young adults, old adults exhibited greater activation for several cortical and subcortical areas. These areas included medial frontal regions implicated in intentional aspects of language and several subcortical areas. Age-related differences were distributed across the hemispheres rather than concentrated in one hemisphere or cortical region. Age-related differences were not seen in right inferior frontal cortex as have been previously seen in other language FMRI paradigms (e.g., Wierenga et al, 2007). Future directions include examining age-related differences in fMRI activation and behavioral performance outside of the scanner (i.e., verbal fluency). OLD VERSUS YOUNG ANOVA RESULTS (p<.005) OLD > YOUNG ACTIVITY = Blue NO significant areas of YOUNG>OLD LEFT FRONTAL RIGHT FRONTAL REFERENCES Cabeza, R. (2002). Hemispheric asymmetry reduction in older adults: The HAROLD model. Psychology and Aging, 17, 85-100. 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. Persson, J., Sylvester, C.-Y. C., Nelson, J. K., Welsh, K. M., Jonides, J., & Reuter-Lorenz, P. A. (2004). Selection requirements during verb generation: differential recruitment in older and younger adults. NeuroImage, 23, 1382-1390. 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, epub ahead of print. 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