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Sperling R, Greve D, Dale A, Killiany R, Holmes J, Rosas HD, Cocchiarella A, Firth P, Rosen B, Lake S, Lange N, Routledge C, Albert M. Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):455-60. PubMed.
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Sperling and colleagues demonstrate how functional brain imaging, behavioral analyses, and pharmacological manipulations can be integrated within an interdisciplinary study of the pharmacology of memory and memory impairments. Their important contribution lays the foundation for future studies which might address several important questions. For example, given the lack of difference in MR effects to the two drugs--despite their very different pharmacological mechanisms—one wonders what the MR data is telling us about the pharmacology of memory, and its neural substrates? Although both drugs appear in these tasks to cause similar memory impairements at the behavior level, presumably they are doing this through very different mechanisms.
The authors note this concern and suggest future work is needed to relate dosages to memory impairments and brain activity. Another route might be to consider a broader range of memory tasks, seeking those for which there are both behavioral and MR differences between the two drugs. Another approach would be to work in parallel with animal studies, where electrophysiological analyses of relevant brain regions might yield greater anatomical and physiological specificity of our understanding of how these two very different drugs affect memory and brain function.
Additional insights into the mechanisms of these pharmacological interventions, and their effects on memory, might also be gained through computational models of neuromodulators and memory. For example, computational models from our lab have already shown how the behavioral effects of scopolamine on learning in classical conditioning can be understood within a computational model of septo-hippocampal cholinergic function (Myers et al. 1996; Myers et al, 1998; see also Gluck & Myers, 2001). Although we know of no analogous computational models of lorazepam, perhaps the Sperling et al. studies might help motivate such work in the future. Neurocomputational modeling provides a methodology both for interpreting existing studies of the neuropharmaracology of memory, as well as for motivating and informing future behavioral, imaging, and neuroimaging research on memory.
See also:
Gluck MA, Myers CE. 2001. Gateway to memory: An introduction to neural network models of the hippocampus and learning. Cambridge, Massachusetts: MIT Press.
References:
Myers CE, Ermita BR, Harris K, Hasselmo M, Solomon P, Gluck MA. A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning. Neurobiol Learn Mem. 1996 Jul;66(1):51-66. PubMed.
Myers C, Ermita B, Hasselmo M, Gluck M. Further implications of a computational model of septohippocampal cholinergic modulation in eyeblink conditioning. . Psychobiology 1998 Mar;26(1):1-20.
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