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The Journal of Neuroscience, December 7, 2005, 25(49):11340-11348; doi:10.1523/JNEUROSCI.2736-05.2005

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Behavioral/Systems/Cognitive
Neural Mechanisms Underlying Probabilistic Category Learning in Normal Aging

Francesco Fera,^1,2 * Thomas W. Weickert,^1 * Terry E. Goldberg,¹ Alessandro Tessitore,^1,3 Ahmad Hariri,^1,4 Sumitra Das,¹ Sam Lee,¹ Brad Zoltick,¹ Martijn Meeter,⁵ Catherine E. Myers,⁶ Mark A. Gluck,⁷ Daniel R. Weinberger,¹ and Venkata S. Mattay¹

¹Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, ²Neuroimaging Laboratory, Neurological Sciences Institute, National Research Council, 87050 Cosenza, Italy, ³Second Division of Neurology, Department of Neuroscience, Second University of Naples, 80131 Naples, Italy, ⁴Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, ⁵Department of Cognitive Psychology, Vrije Universiteit Amsterdam, NL 1081 BT Amsterdam, The Netherlands, and ⁶Department of Psychology and ⁷Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102

Probabilistic category learning engages neural circuitry that includes the prefrontal cortex and caudate nucleus, two regions that show prominent changes with normal aging. However, the specific contributions of these brain regions are uncertain, and the effects of normal aging have not been examined previously in probabilistic category learning. In the present study, using a blood oxygenation level-dependent functional magnetic resonance imaging block design, 18 healthy young adults (mean age, 25.5 ± 2.6 years) and 15 older adults (mean age, 67.1 ± 5.3 years) were assessed on the probabilistic category learning "weather prediction" test. Whole-brain functional images acquired using a 1.5T scanner (General Electric, Milwaukee, WI) with gradient echo, echo planar imaging (3/1 mm; repetition time, 3000 ms; echo time, 50 ms) were analyzed using second-level random-effects procedures [SPM99 (Statistical Parametric Mapping)]. Young and older adults displayed equivalent probabilistic category learning curves, used similar strategies, and activated analogous neural networks, including the prefrontal and parietal cortices and the caudate nucleus. However, the extent of caudate and prefrontal activation was less and parietal activation was greater in older participants. The percentage correct and reaction time were mainly positively correlated with caudate and prefrontal activation in young individuals but positively correlated with prefrontal and parietal cortices in older individuals. Differential activation within a circumscribed neural network in the context of equivalent learning suggests that some brain regions, such as the parietal cortices, may provide a compensatory mechanism for healthy older adults in the context of deficient prefrontal cortex and caudate nuclei responses.

Key words: prefrontal cortex; parietal cortex; caudate nucleus; aging; category learning; compensation

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Received July 1, 2005; revised October 20, 2005; accepted October 23, 2005.

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