‘‘What’’ and ‘‘Where’’ in Visual Working Memory: A Computational Neurodynamical Perspective for Integrating fMRI and Single-Neuron Data Gustavo Deco 1 , Edmund T. Rolls 2 , and Barry Horwitz 3 Abstract & Single-neuron recordings, functional magnetic resonance imaging (f MRI) data, and the effects of lesions indicate that the prefrontal cortex (PFC) is involved in some types of working memory and related cognitive processes. Based on these data, two different models of the topographical and functional organization of the PFC have been proposed: organization-by-stimulus-domain, and organization-by-process. In this article, we utilize an integrate-and-fire network to model both single-neuron and fMRI data on short-term memory in order to understand data obtained in topologi- cally different parts of the PFC during working memory tasks. We explicitly model the mechanisms that underlie working- memory-related activity during the execution of delay tasks that have a ‘‘what’’-then-‘‘where’’ design (with both object and spatial delayed responses within the same trial). The model contains different populations of neurons (as found experimentally) in attractor networks that respond in the delay period to the stimulus object, the stimulus position, and to combinations of both object and position information. The pools are arranged hierarchically and have global inhi- bition through inhibitory interneurons to implement competi- tion. It is shown that a biasing attentional input to define the current relevant information (object or location) enables the system to select the correct neuronal populations during the delay period in what is a biased competition model of attention. The processes occurring at the AMPA and NMDA synapses are dynamically modeled in the integrate-and-fire implementation to produce realistic spiking dynamics. It is shown that the f MRI data characteristic of the dorsal PFC and linked to spatial processing and manipulation of items can be reproduced in the model by a high level of inhibition, whereas the fMRI data characteristic of the ventral PFC and linked to object processing can be produced by a lower level of inhibition, even though the network is itself topographically homogeneous with no spatial topology of the neurons. This article, thus, not only presents a model for how spatial versus object short-term memory could be implemented in the PFC, but also shows that the fMRI BOLD signal measured during such tasks from different parts of the PFC could reflect a higher level of inhibition dorsally, without this dorsal region necessarily being primarily spatial and the ventral region object-related. & INTRODUCTION The aim of this article is to integrate, via a large-scale neuronal network model that generates the dynamics and synaptic processing of neurons in an integrate-and- fire implementation, single-neuron and functional mag- netic resonance imaging (fMRI) measurements of the prefrontal cortex (PFC) associated with visual working memory processing. One of the aims of this integration is to help interpret the f MRI signals recorded in topograph- ically separate parts of the PFC and, more generally, to provide a fundamental approach to understanding fMRI signals. The PFC is involved in at least some types of working memory and related processes such as planning (Fuster, 2000; Goel & Grafman, 1995; Goldman-Rakic, 1995; Goldman-Rakic, 1996), as shown by single-neuron (Fu- nahashi, Bruce, & Goldman-Rakic, 1989), neuroimaging (Ungerleider, Courtney, & Haxby, 1998), and lesion studies (Levy & Goldman-Rakic, 1999; Goldman-Rakic, 1987). Working memory refers to an active system for maintaining and manipulating information in mind, held during a short period of time (usually seconds) (Badde- ley, 1986). Two models of the topographical and functional organization of the PFC have been proposed (see Miller, 2000, for a review). The first model proposes organization-by-stimulus-domain, with spatial (‘‘where’’) working memory supported by the dorsolateral PFC in the neighborhood of the principal sulcus (Brodmann’s area [BA] 46/9 in the middle frontal gyrus [MFG]); and object (‘‘what’’) working memory supported by the ventrolateral PFC on the lateral convexity (BA 45 in the inferior frontal gyrus [IFG]). Some, but not all, fMRI studies in humans and single-cell data in primates 1 Institucion Catalana de Recerca; Estudis Avanc¸ats (ICREA)and Universitat Pompeu Fabra, 2 University of Oxford, 3 National Institutes of Health © 2004 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 16:4, pp. 683–701