Scott Small, M.D.Professor, Neurology
Member, The Kavli Institute for Brain Science
Tel +1 212-305-9194
Area of Research
Cognitive neuroscience of working memory and control and of category learning and conceptual representations.
The hippocampal formation functions as a three-dimensional network. We have been developing MRI approaches that allow us to interrogate the hippocampus as a circuit in humans and, most recently, in mice. Our interests are split between using these imaging approaches to understand how the hippocampus functions during normal associative memory, and how the hippocampus fails during aging and Alzheimer’s disease. We have focused on the longitudinal axis of the hippocampus in our studies of normal memory where we have human subjects process auditory and visual stimuli, in isolation or paired in time. Results from these studies suggest specific circuit mechanisms for how the hippocampus encodes and combines information during associative memory. We are currently extending this area of investigation into mice, which will allow us to uncover potential cellular and molecular mechanisms that underlie these circuit mechanisms.
We have focused on the transverse axis of the hippocampal formation in our efforts to understand how the hippocampus fails in aging and Alzheimer’s disease. Toward this goal, we have developed novel imaging approaches that measure hippocampal function with microscopic resolution. These approaches allow us to assess the multiple hippocampal subregions that make up the transverse circuit-- individually to pinpoint the site of dysfunction, and simultaneously to correct for circuit-wide effects. We have used this approach to generate patterns of hippocampal dysfunction in humans with Alzheimer’s disease and normal aging, as well as in mouse models with Alzheimer’s disease and normal aging. Taken together, the results suggest that MRI maps of hippocampal dysfunction can dissociate causes of memory decline. We are currently testing whether these MRI approaches can be used as a diagnostic tool for early Alzheimer’s disease, and whether these MRI approaches can be exploited for drug development.
Small, S.A. (2002). The longitudinal axis of the hippocampal formation: Its anatomy, circuitry and role in cognitive function. Rev. Neurosci., 13: 183-194
Small, S.A., Tsai, W.Y., DeLaPaz, R., Mayeux, R., Stern, Y. (2002). Imaging hippocampal function across the human life span: Is memory decline normal or not? Ann. Neurol., 51: 290-295.
Small, S.A., Nava, A.S., Tsai, W.Y., DeLaPaz, R., Mayeux, R., Stern, Y. (2001). Circuit mechanisms underlying memory encoding and retrieval in the long axis of the hippocampal formation. Nature Neuro., 442-449.
Small, S.A., Wu, E.X., Bartsch, D., Perera, G.M., Lacefield, C.O., DeLaPaz, R., Mayeux, R., Stern, Y., and Kandel, E.R. (2000). Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice. Neuron, 28: 653-664.
Small, S.A., Perera, G.M., DeLaPaz, R., Mayeux, R., and Stern, Y. (1999). Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer’s disease. Ann. Neurol., 45: 466-472.