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Methods 44 (2008) 287–288

Guest Editor’s Introduction

Models in memory research

The notion that the mind and cognitive abilities includ-ing memory are present in different areas of the brain andalso other organs has a long tradition; it first was consid-ered by pre-Socratic philosophers like Demokrit (460–371BC) and Plato (428–347 BC). Demokrit presented thehypothesis that soul, psyche, and vitality together formthe mind, which is composed of great atoms that are con-centrated in the brain, the heart, and the liver. On the basisof Demokrit’s theory, Plato assumed that the brain is theruler over the rest of the body. Galen (129–199) furtherexpanded on the old Greek hypotheses and proposed theconcept of different cells being responsible for the mind.The first cell was called the sensus communis (the conflu-ence of all sensorial information) and was localized in thefrontal lateral ventricles, since at this time the cortex wasconsidered a protective shell. The content of the first cellwas then combined with phantasm and imagination andsupported by motivation and rational thinking. Thesesequential processes finally resulted in the planning andexecution of action accomplished by the posterior hornsof the lateral ventricles. This action sequence could be seenas the first proposal of a neuronal network, which eventu-ally became the basis for the current memory theories thatevolved from intermediary hypotheses of brain functionand organization (e.g., Franz Josef Gall (1758–1828)). Inaddition to these theoretical approaches, understandingthe physiological background of neuronal activation andthe interaction of blood supply and energy metabolism inthe brain [1] was a major step towards the meanwhile devel-oped knowledge of brain and specifically memory function.Numerous molecular mechanisms form the basis for theability to memorize states or things, among which theNF-jB transcription factor as a direct signaling mechanismin the regulation of gene expression involved in long-termmemory seems to have a pivotal role [2]. Another exampleis the concept of long-term potentiation that is most effec-tively induced by high-frequency stimuli, synaptic facilita-tion, and molecular mechanisms such as N-methyl-D-aspartate (NMDA) receptor-induced calcium cascade andprotein synthesis (e.g., [3]). The neurobiological substrateof memories resides in activity-driven modifications of syn-aptic strength and structural remodeling of neural net-works activated during learning [4].

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In addition to the molecular basis of memory functionsstudied in cell cultures or alterations of diseases that causesmemory decline in different animal models of neurodegen-erative diseases (e.g., [5]), cognitive neuroscience includingneuropsychology has been the leader in establishing theo-retical models of memory [6]. To facilitate the theoreticalunderstanding of human memory, the taxonomy of mem-ory and the suggested models of interaction between thesetheoretically distinct functions have been major steps [7].

It is impossible to give an overview of the large varietyof memory models and descriptions in a single issue. Thereare several historical ways to approach the understandingof memory, which basically comprises the ability to store,retain, and subsequently retrieve information. One way isto look into the ‘‘microscopic” basis of memory by study-ing the molecular basis of memory in a neuronal microen-vironment in vitro or in vivo (e.g., [8,9]). Another approachis to look into the brains from those with neurodegenera-tive diseases and compare molecular [10,11] and functionalchanges [12] with normal brains. This will be the focus ofthe first part of this issue. During the last century, lesionstudies in humans [13] and non-human primates [14], whichmight in contrast be seen as a ‘‘macroscopic approach”, re-sulted in the current understanding of the brain as a dy-namic neuronal network with multiple specialized nodes,an understanding that established the basis for the defini-tion of theoretical memory models nowadays [15]. The ra-pid development of non-invasive functional imaging in thelast two decades made it possible to further delineate differ-ent functions and thereby generate new, much more sophis-ticated memory models. In this issue the second part willfocus on these functional imaging techniques, includingcorrelative methods (i.e., EEG, fMRI, PET [16]) and inter-ference methods (TMS and direct current electrical stimu-lation [17]) and will be completed with an overview oflarge-scale modeling of memory processes [18].

References

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Neurosci. 24 (2006) 1507–1516.[3] V.R. Rao, S. Finkbeiner, Trends Neurosci. 30 (2007) 284–291.

288 Guest Editor’s Introduction / Methods 44 (2008) 287–288

[4] E. Bruel-Jungerman, S. Davis, S. Laroche, Neuroscientist 13 (2007)492–505.

[5] A. Parachikova, K.E. Nichol, C.W. Cotman, Short-term exercise inaged Tg2576 mice alters neuroinflammation and improves cognition,Neurobiol. Dis., in press.

[6] A. Baddeley, Trends. Cogn. Sci. 4 (2000) 417–423.[7] E. Tulving, Hum. Neurobiol. 6 (1987) 67–80.[8] D. Makhracheva-Stepochkina, S. Frey, J.U. Frey, V. Korz, Spatial

learning in the holeboard impairs an early phase of long-termpotentiation in the rat hippocampal CA1-region, Neurobiol. Learn.Mem., in press.

[9] J.M. Pedraza, J. Paulsson, Science 319 (2008) 339–343.[10] M. Otto, P. Lewczuk, J. Wiltfang, Neurochemical approaches of

cerebrospinal fluid diagnostics in neurodegenerative diseases, Meth-ods 44 (2008) 289–298.

[11] A.V. Thomas, O. Beresovska, B.T. Hyman, C.A.F. von Arnim,Visualizing interaction of proteins relevant to Alzheimer’s disease inintact cells, Methods 44 (2008) 299–303.

[12] A. Drzezga, Concept of functional imaging of memory decline in AD,Methods 44 (2008) 304–314.

[13] P. Broca, Bull. Soc. Anat. Paris 36 (1861) 330–357.[14] P. Goldman-Rakic, NeuroImage 11 (2000) 451–457.[15] F.M. Mottaghy, Neuroscience 139 (2006) 85–90.[16] T.D. Poeppel, B.J. Krause, Functional imaging of memory processes

in humans: positron emission tomography and functional magneticresonance tomography, Methods 44 (2008) 315–328.

[17] R. Sparing, F.M. Mottaghy, Noninvasive brain stimulation withtranscranial magnetic or direct current stimulation (TMS/tDCS)—from insights into human memory to therapy of its dysfunction,Methods 44 (2008) 329–337.

[18] B. Horwitz, J.F. Smith, A link between neuroscience and informatics:large scale modeling of memory processes, Methods 44 (2008) 338–347.

Felix M. MottaghyDepartment of Nuclear Medicine,

University Hospital KU Leuven, Herestraat 49,

B-3000 Leuven, Belgium

E-mail address: felix.mottaghy@uz.kuleuven.ac.be