We report a computer simulation of the visuospatial delayed-response experiments of Funahashi et al. (1989), using a firing-rate model that combines intrinsic cellular bistability with the recurrent local network architecture of the neocortex. In our model, the visuospatial working memory is stored in the form of a continuum of network activity profiles that coexist with a spontaneous activity state. These neuronal firing patterns provide a population code for the cue position in a graded manner. We show that neuronal persistent activity and tuning curves of delay-period activity (memory fields) can be generated by an excitatory feedback circuit and recurrent synaptic inhibition. However, if the memory fields are constructed solely by network mechanisms, noise may induce a random drift over time in the encoded cue position, so that the working memory storage becomes unreliable. Furthermore, a "distraction" stimulus presented during the delay period produces a systematic shift in the encoded cue position. We found that the working memory performance can be rendered robust against noise and distraction stimuli if single neurons are endowed with cellular bistability (presumably due to intrinsic ion channel mechanisms) that is conditional and realized only with sustained synaptic inputs from the recurrent network. We discuss how cellular bistability at the single cell level may be detected by analysis of spike trains recorded during delay-period activity and how local modulation of intrinsic cell properties and/or synaptic transmission can alter the memory fields of individual neurons in the prefrontal cortex.

Neuroimaging studies have suggested the involvement of ventrolateral, dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working (WM) and long-term memory (LTM). The current study used functional magnetic resonance imaging (fMRI) to directly compare whether these PFC regions show selective activation associated with one memory domain. In a within-subjects design, subjects performed the n-back WM task (two-back condition) as well as LTM encoding (intentional memorization) and retrieval (yes–no recognition) tasks. Additionally, each task was performed with two different types of stimulus materials (familiar words, unfamiliar faces) in order to determine the influence of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA 46/9)

We apply nine analytic methods employed currently in imaging neuroscience to simulated and actual BOLD fMRI signals and compare their performances under each signal type. Starting with baseline time series generated by a resting subject during a null hypothesis study, we compare method performance with embedded focal activity in these series of three different types whose magnitudes and time courses are simple, convolved with spatially varying hemodynamic responses, and highly spatially interactive. We then apply these same nine methods to BOLD fMRI time series from contralateral primary motor cortex and ipsilateral cerebellum collected during a sequential finger opposition study. Paired comparisons of results across methods include a voxel-specific concordance correlation

This experiment used functional Magnetic Resonance Imaging to examine the relation between individual differences in cognitive skill and the amount of cortical activation engendered by two strategies (linguistic vs. visual–spatial) in a sentence– picture verification task. The verbal strategy produced more activation in languagerelated cortical regions (e.g., Broca’s area), whereas the visual–spatial strategy produced more activation in regions that have been implicated in visual–spatial reasoning (e.g., parietal cortex). These relations were also modulated by individual differences in cognitive skill: Individuals with better verbal skills (as measured by the reading span test) had less activation in Broca’s area when they used the verbal strategy. Similarly, individuals with better visual–spatial skills (as measured by the Vandenberg, 1971, mental rotation test) had less activation in the left parietal cortex when they used the visual-spatial strategy. These results indicate that language and visual–spatial processing are supported by partially separable networks of cortical regions and suggests one basis for strategy selection: the minimization of cognitive workload. © 2000 Academic Press

Visual short-term memory in humans and animals is frequently assessed using delayed matching to sample (DMTS) and delayed nonmatching to sample (DNMTS) tasks across variable delay intervals. Although these tasks depend on certain common mechanisms, there are behavioral differences between them, and neuroimaging provides a means of assessing explicitly whether this is underpinned by differences at a neural level. Findings of delay-dependent deficits, after lesions in humans and animals, suggest that the neural implementation of these tasks may also critically depend on the delay interval. In this study we determined whether there were differential neural responses associated with DMTS and DNMTS tasks at two different delay intervals using functional magnetic resonance imaging. Ten healthy volunteers were studied under four test conditions: DMTS and DNMTS at 5 and 15 sec delay. The main effect of DMTS compared with DNMTS across both delay Delayed matching to sample (DMTS) and delayed nonmatching to sample (DNMTS) paradigms are widely used to study visual memory in humans and animals. Both tasks require subjects to hold a visual stimulus “on line ” over a delay interval before responding to a choice of stimuli. In DMTS, subjects must select the familiar stimulus; in DNMTS they must select the novel stimulus. Successful performance of both tasks depends on the integrity of inferior temporal regions (Gross, 1973; Mishkin, 1982; Horel et al., 1987), posterior perceptual cortex, and medial temporal lobe structures (Zola-Morgan and Squire, 1985;

Recent theoretical models based on cellular processes in parahippocampal structures show that persistent neuronal spiking in the absence of stimulus input is important for encoding. The goal of this study was to examine in humans how sustained activity in the parahippocampal gyrus may underlie long-term encoding as well as active maintenance of novel information. The relationship between long-term encoding and active maintenance of novel information during brief memory delays was studied using functional magnetic resonance imaging (fMRI) in humans performing a delayed matching-to-sample (DMS) task and a post-scan subsequent recognition memory task of items encountered during DMS task performance. Multiple regression analyses revealed fMRI activity in parahippocampal structures associated with the active maintenance of trial-unique visual information during a brief memory delay. In addition to a role in active maintenance, we found that the subsequent memory for the sample stimuli as measured by the post-scan subsequent recognition memory task correlated with activity in the parahippocampal gyrus during the delay period. The results provide direct evidence that encoding mechanisms are engaged during brief memory delays when novel information is actively maintained. The relationship between active maintenance during the delay period and long-term subsequent memory is consistent with current theoretical models and experimental data that suggest that long-term encoding is enhanced by sustained parahippocampal activity. Key words: memory; parahippocampal; neuroimaging; medial temporal lobe; delayed match to sample; computational modeling

Foraging- and feeding-related behaviors across eumetazoans share similar molecular mechanisms, suggesting the early evolution of an optimal foraging behavior called area-restricted search (ARS), involving mechanisms of dopamine and glutamate in the modulation of behavioral focus. Similar mechanisms in the vertebrate basal ganglia control motor behavior and cognition and reveal an evolutionary progression toward increasing internal connections between prefrontal cortex and striatum in moving from amphibian to primate. The basal ganglia in higher vertebrates show the ability to transfer dopaminergic activity from unconditioned stimuli to conditioned stimuli. The evolutionary role of dopamine in the modulation of goal-directed behavior and cognition is further supported by pathologies of human goal-directed cognition, which have motor and cognitive dysfunction and organize themselves, with respect to dopaminergic activity, along the gradient described by ARS, from perseverative to unfocused. The evidence strongly supports the evolution of goal-directed cognition out of mechanisms initially in control of spatial foraging but, through increasing cortical connections, eventually used to forage for information.

1 I. INTRODUCTION 2 A. An Integrative Strategy 2 B. A State Space Model of the Brain-Mind 3 C. Caveat Lector 4 II. THE PHENOMENOLOGY AND PSYCHOPHYSIOLOGY OF WAKING, SLEEPING AND DREAMING 5 DREAMING and the BRAIN: Toward a Cognitive Neuroscience of Conscious States http://home.earthlink.net/~sleeplab/bbs/BBS.html (1 of 222) [1/6/2000 2:48:02 PM] A. Early findings of distinct differences between REM and NREM mentation 6 B. Overview of the NREM-REM Sleep Mentation Controversy 12 1. REM Sleep Dreaming is not Qualitatively Unique 13 2. The Relationship Between Dream Features and Dream Report Length 17 C. Methodological Considerations in the Study of Dreaming 21 1. The Reduction of Psychological States to Narrative Reports 21 2. The Sleep Laboratory Environment 26 3. The Question of "Similarity" and "Difference" 29 4. The Source and Fate of Dream Memory 33 5. Type I vs. Type II Statistical Analyses 39 6. The Need for New Approaches 40 III. THE COGNITIVE NEUROSCIENCE OF WAKING, SLEEPING AN...

Schizophrenia has long been considered a disease of brain function that is reflected in a host of cognitive impairments in addition to the classic symptoms on which the diagnosis is based. For example, patients with schizophrenia show a range of cognitive deficits, particularly in measures of memory and executive functions (1), and differences in brain structure (2) and functional activity in regions thought to support such functions (3). Emphasis has been placed on the dorsolateral prefrontal cortex and its relation to working memory (3–6), a set of cognitive processes involved in actively maintaining and manipulating information in the mind in order to guide behavior (e.g., reference 7) and critical to high-level cognition (e.g., language, problem-solving, and reasoning). The relevance of working memory dysfunction to schizophrenia is evident

The dominant cognitive theory of working memory (WM) postulates a strict architectural segregation between components responsible for the short-term active maintenance of information and those responsible for the control and coordination of that information. Cognitive neuroscience research has provided strong evidence that the prefrontal cortex (PFC) serves as an important neural substrate of WM. However, the literature is mixed as to whether PFC should be considered a storage or control component. A theory is presented that attempts to resolve this conflict by postulating that PFC represents and actively maintains context information. These maintained representations provide a mechanism of control by serving as a top-down bias on the local competitive interactions that occur during processing. As such, it is suggested that storage and control functions are integrated within PFC. This theory is implemented as connectionist computational model. Simulation studies are described which demonstrate that the model can account for a wide range of behavioral data associated with performance of a simple task paradigm that probes both the storage and control functions of WM. Two neuroimaging studies are then presented which directly test the predictions of the model regarding the role of PFC in context processing. Taken together, the results provide new insights into the relationship between storage and control in WM, and the role of PFC in subserving these functions. i Working Memory and Prefrontal Cortex