Introduction Working memory refers to a brain system that provides temporary storage and manipulation of the information necessary for such complex cogni- tive tasks as language comprehension and learning. This brain system requires the simultaneous storage and processing of information. The function of the phonological loop, which stores and rehearses speech-based information 1 is one of the working memory systems. Broca’s area (Brodmann 44/45 in the left inferior frontal lobe) was found to be involved in the phonological loop in studies using positron emission tomography (PET) 2 and in the covert speech tasks using functional magnetic resonance imaging (fMRI). 3–5 Recently, in the spatial working memory task, the sustained activity after the visual presentation was detected in Broca’s area using fMRI. 6 The activation in Broca’s area in the spatial task may have been due to verbalization that the subjects may have used in the spatial memory task. Unless this component can be controlled or excluded one cannot conclude that Broca’s area is involved in spatial memory. In psychology it is difficult to define the termination of a ‘sustained’ phonological process. In particular, in working memory studies using multiple-task trials during an experiment, 6 it is possible to alter naturally responses of the memory processing. Animal studies involving hippocampal lesions suggested that the hippocampal formation is involved in spatial working memory. 7,8 The hippocampal formation is located in the medial part of the temporal lobe of the human brain. The hippocampus is connected directly and indirectly, in both afferent and efferent directions, with various other parts of the brain, and thus can be considered the center of a more extended system. 9 Clinical lesion studies and neuropathological examinations have shown that the human hippocampal formation is involved in learning and memory function. 10,11 Human functional imaging studies showed activation in the hippocampal formation during memory task period. 12,13 However, a sustained response in human hippocampus has not been observed in any studies. We investigated the hypothesis that human hippocampus is involved in working memory. The sensitivity of fMRI, espe- cially at high fields, 14–17 has advanced sufficiently to permit the examination of this hypothesis. In the present study, blood oxygen level depen- dent (BOLD) 17 based fMRI at 4 Tesla was performed in conjunction with a word memory task on seven healthy right-handed volunteers. The echo planar imaging (EPI) time courses of cerebral responses during and after a single task period were monitored. Cognitive Neuroscience and Neuropsychology 1111 2 3 4 5 6 7 8 9 10111 1 2 3 4 5 6 7 8 9 20111 1 2 3 4 5 6 7 8 9 30111 1 2 3 4 5 6 7 8 9 40111 1 2 3 4 5 6 7 8 9 50111 1 2 3 4 5 6111p © Rapid Science Ltd Vol 9 No 6 20 April 1998 1041 TEMPORAL behavior of activation associated with the neural substrate of human memory function was inves- tigated during and after an auditorily instructed word memory task using multislice functional magnetic reso- nance imaging. The hippocampal formation, which is involved in human memory function, displayed a long- term sustained response that persisted significantly (~90 s) beyond the duration of the memory task. This sustained period was ~two-fold longer than the dura- tion of the post-task activation observed in auditory areas and Broca’s area, which are involved in the phono- logical loop of the verbal working memory. These obser- vations suggest that the hippocampal memory processing involves sustained activation in the transi- tional function for the long-term memory over the working memory period. NeuroReport 9: 1041–1047 © 1998 Rapid Science Ltd. Key words: Brain; Cerebral multiphasic sustained response; Echo-planar imaging (EPI); Functional magnetic resonance imaging (fMRI); Hippocampus; Humans; Long-term sustained response; Memory; Network Human hippocampal long-term sustained response during word memory processing Toshinori Kato, CA Peter Erhard, Yoshihiro Takayama, John Strupp, Tuong Huu Le, Seiji Ogawa 1 and Kamil Ugurbil Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, 385 East River Road, Minneapolis, MN 55455, USA; 1 Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974, USA CA Corresponding Author Website publication 27 March 1998 NeuroReport 9, 1041–1047 (1998)