48o of information about the organization and anatomy o to experimental analysis.Withoutdir omhatcognlonis9oLni that there are tand the path from per mation-pro ample.the vi a Mountcastle on somatic sensatior id Hubel and om ent inaugurated the contnb mad eurons and to o tes ge popu specif tive processes Tounderstand the neural organization ion not onlyth e as p ork prop aking)a nd patt k pro the This dboth inp of indi pro sing in the dual ells are helpfu rCioentnihge led toa ns of syat the system is capable by Sa erties n lay at th NIH.Walle Nauta :9 ct of co s on the d to documen ly the rema kable ress tha omy and function led to the system learns ging te etic r vie d through the he first compon nt is concemned This is the em of r 2acineco in no By com mpor wit es an fmemory. tes of sens ry processing.motor actions,and cogni- 196 and 1970s he was also r wed inte uestior ory s stored mental proc o encor mpa e is the of hum stion Franz Jo eph Gall, who made twe for iveand issue ish mind brain asmFn hased on his s with brai e that natooicalstudies that the the organ of the and suct studi the t co ains d centers tha wn for lang hy Pie rre Pau d the idea of cortical localization.Gall assert h FoL eac ing Br a and We th even a bi was in etiveness,are local Hans all was not anexperimentalist.He ed the stud sequences of brain lesions proved to be a rich source experimental animals and instead attempted to locate Neuron 446 behavior, they had to come to grips with the fact that of information about the organization and anatomy of most mental processes were still largely inaccessible higher functions, including memory. Lesionstudies have to experimental analysis. Without direct access to the shown that cognition is not unitary but that there are neural substrates of internal representations it was diffi- several cognitive systems, each with independent infor￾cult, if not impossible, to understand the path from per- mation-processing modules. For example, the visual ception to action. At about this time, the work of Vernon system of primates, a prototypicalcognitive system, has Mountcastle on somatic sensation, David Hubel and specialized anatomical pathways for processing infor￾Torsten Wiesel on vision, and Edward Evarts on the mation about color, form, and movement. control of movement inaugurated the neuronal analysis Finally, computational science has made a distinctive of perception and voluntary action. Moreover, during contribution to cognitive neuroscience. Computers made the 1970s, Evarts and Mountcastle developed tech- it possible to model the activity of large populations of niques for studying the activity of single cells in the neurons and to begin to test ideas about how specific brains of awake, behaving monkeys. In their hands, and components of the brain contribute to particular cogni￾in work that followed by Robert Wurtz, Apostolos Geor- tive processes. To understand the neural organization gopoulos, William Newsome, and others, single-unit of a complex behavior like speech, we must understand studies in monkeys led to the first correlations between not only the properties of individual cells and pathways cognitive processes (such as perception, attention, and but also the network properties of functional circuits decision making) and patterns of firing of individual cells in the brain. While network properties arise from the in specific brain regions. This work changed the way properties of individual neurons in the network, they behavior was studied both in experimental animals and need not be explainable in terms of the behavior of in humans; the focus now was on the information pro- individual cells. Computational approaches are helpful cessing in the brain that leads to behavior. for characterizing the system as whole, for obtaining The need for greater anatomical knowledge led to a formal descriptions of what the system is capable of renaissance of neuroanatomy, evident in the develop- doing, and for determining how the interacting constit- ment of new techniques for tracing connections be- uent elements account for system properties. tween neurons by Sanford Palay at the NIH, Walle Nauta This review focuses on the topic of memory, but one at MIT, Matthew and Jennifer LaVail at Harvard, and aspect of cognitive neuroscience. We have not at- Max Cowan at Washington University. The search for tempted to document fully the remarkable progress that new neuroanatomical methods and the need to bridge has been achieved in our understanding of how the anatomy and function led to the application of neuro- nervous system learns and remembers. Rather, we fo- imaging techniques (positron emission tomography [PET] cus on two key components in the study of memory, as scanning and functional magnetic resonance imaging viewed through thework that the three of us have carried [MRI]) to cognitive problems. This major advance, pio- out with our colleagues during the past severaldecades. neered by Marcus Raichle and Michael Posner and by The first component is concerned with analyzing what Seiji Ogawa, Ken Kwong, and others, made it possible memory is, where it is stored, and what brain systems to relate changes in activity in large populations of neu- are involved. This is the systems problem of memory. rons to specific cognitive acts in living humans. By com- The second component of memory is concerned with paring the results of cellular recordings in nonhuman analyzing how memory is stored. This is the molecular primates and the results of neuroimaging in humans, it problem of memory. has become possible to study directly the neural corre￾lates of sensory processing, motor actions, and cogni￾tive processes. Where Are Memories Stored? In the 1960s and 1970s, there was also renewed inter- The question of where memory is stored emerged at est in the traditional discipline of neuropsychology. Early the beginning of the 19th century as part of the larger students of brain and behavior like Karl Lashley and question—to what degree can any mental process be Donald Hebb used the term neuropsychology broadly localized within the brain? The first person to address to encompass studies of experimental animals as well this question was Franz Joseph Gall, who made two as studies of humans. In this sense, cognitive neurosci- major conceptual contributions. First, Gall attempted to ence is the modern forum for the same topics and issues abolish mind–brain dualism. He argued, based on his that engaged Lashley and Hebb earlier in this century. Studies of patients with brain injury or disease that af- anatomical studies, that the brain is the organ of the mind. Second, he appreciated that the cerebral cortex fects mental function have always been a vital part of neuropsychology, and such studies formed one of the is not homogenous but contains distinctive centers that control specific mental functions. Gall therefore pro- foundations of cognitive neuroscience. As first clearly shown for language by Pierre Paul posed the idea of cortical localization. Gall asserted that Broca in 1863, patients with lesions of specific regions the brain does not act as a unitary organ but is divided of the brain exhibit quite specific cognitive deficits. Fol- into at least 27 faculties (others were added later), each lowing Broca and Wernicke, the neuropsychological at- corresponding to a specific mental faculty. He thought tempt at regional localization remained strong in Europe that even the most abstract and complex of human and in Canada but was in good part neglected in the traits, such as generosity and secretiveness, are local￾United States, with the exception of the work of Arthur ized to discrete areas of the brain. Benton, Hans-Lukas Teuber, and Norman Geschwind. Gall was not an experimentalist. He rejected the study As we shall see, continuing study of the behavioral con- of neurological lesions and the surgical manipulation of sequences of brain lesions proved to be a rich source experimental animals and instead attempted to locate