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
Hemispheric Asymmetry Reductions in Older Adults
during Category Exemplar GenerationMichelle 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 1,2,5Department of
Veterans Affairs Rehabilitation Research and
Development Brain Rehabilitation Research Center
at the Malcom Randall VA Medical
Center1University of Florida Departments of
Clinical and Health Psychology2, and
Psychology3,and McKnight Brain Institute4,
Gainesville, FloridaPresented at the February
2008 International Neuropsychological Society
Conference, Waikoloa, HawaiiThis poster is
available on the Web at http//www.BIRC.phhp.ufl.e
du
RESULTS
METHODS
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 gt 27 on the MMSE. See Table 1
for descriptive demographics. Table 1. Group
Demographics
LEFT RIGHT BASAL GANGLIA
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 (gt65 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 (plt.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.
RIGHT THALAMUS
Subject Group (age range) Mean Age (SD) Sex (FM) Years Education Mean (SD) MMSE total Mean (SD)
OLD 71.3 (6.2) 913 16.3 (3.2) 29.4 (0.9)
YOUNG 25.5 (4.5) 1210 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, TR1700 ms, TE25
  ms, flip angle70o. 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-SMAdorsal caudate nucleusventral
  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).

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 (plt.005) OLD gt
YOUNG ACTIVITY Blue NO significant areas of
YOUNGgtOLD
RIGHT FRONTAL
LEFT 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 RRD Center of
Excellence Grant F2182C and Research Career
Scientist Award (Crosson) McKnight Brain
Institute of University of Florida E. F. McKnight
Grants