Humans and monkeys have similar capacities to discriminate the frequencies of mechanical sinusoids delivered to their hands in the range that corresponds to the sense of flutter (10–50 Hz). Previous studies showed that monkeys can discriminate whether comparison stimuli are higher or lower in frequency than a base stimulus that does not vary from trial to trial during an experiment. We verified this result in two monkeys trained in this manner. To confirm that these animals were able to discriminate, we tested them in a variant of the task in which the frequency of the base stimulus changed randomly from trial to trial. The monkeys failed to discriminate in this new testing mode; instead they seemed to categorize the comparison stimuli, ignoring the base stimulus. After further training in the randomized base condition, the two monkeys learned to discriminate accurately. We then explored how the stimulation

It is widely held that the prefrontal cortex is important for working memory. It has been suggested that the inferior convexity (IC) may play a special role in working memory for form and color (Wilson et al., 1993). We have therefore assessed the ability of monkeys with IC lesions to perform visual pattern association tasks and color-matching tasks, both with and without delay. In experiment 1, six monkeys were trained on a visual association task with delays of up to 2 sec. Conservative IC lesions that removed lateral area 47/12 in three animals had no effect on the task. Further experiments showed that these lesions had no effect on the postoperative new learning of a It is widely held that the prefrontal cortex is involved in working memory (Goldman-Rakic, 1987, 1996; Funahashi and Kubota, 1994). In animal-based research, working memory refers to the ability to hold information “on-line ” to guide behavior in the absence of

Macaque monkeys were tested on a delayed-match-to-multiple-sample task, with either a limited set of well trained images (in randomized sequence) or with never-before-seen images. They performed much better with novel images. False positives were mostly limited to catch-trial image repetitions from the preceding trial. This result implies extremely effective one-shot learning, resembling Standing’s finding that people detect familiarity for 10,000 once-seen pictures (with 80 % accuracy) (Standing, 1973). Familiarity memory may differ essentially from identification, which embeds and generates contextual information. When encountering another person, we can say immediately whether his or her face is familiar. However, it may be difficult for us to identify the same person. To accompany the psychophysical findings, we present a generic neural network model reproducing these behaviors, based on the same conservative Hebbian synaptic plasticity that generates delay activity identification memory. Familiarity becomes the first step toward establishing identification. Adding an inter-trial reset mechanism limits false positives for previous-trial images. The model, unlike previous proposals, relates repetition–recognition with enhanced neural activity, as recently observed experimentally in 92 % of differential cells in prefrontal cortex, an area directly involved in familiarity recognition. There may be an essential functional difference between enhanced responses to novel versus to familiar images: The maximal signal from temporal cortex is for novel stimuli, facilitating additional sensory processing of newly acquired stimuli. The maximal signal for familiar stimuli arising in prefrontal cortex facilitates the formation of selective delay activity, as well as additional consolidation of the memory of the image in an upstream cortical module. Key words: familiarity recognition; memory; one-shot learning; neural networks; multiple DMS; psychophysics

The prefrontal cortex (PFC) is important for flexible, context-dependent behavioral control. It also plays a critical role in short-term memory maintenance. Though many studies have investigated these functions independently, it is unclear how these two very different processes are realized by a single brain area. To address this, we trained two monkeys on two variants of an object sequence memory task. These tasks had the same memory requirements but differed in how information was read out and used. For the “recognition ” task, the monkeys had to remember two sequentially presented objects and then release a bar when a matching sequence was recognized. For the “recall ” task, the monkeys had to remember the same sequence of objects but were instead required to recall the sequence and reproduce it with saccadic eye movements when presented with an array of objects. After training, we recorded the activity of PFC neurons during task performance. We recorded 222 neurons during the recognition task, 177 neurons during the recall task, and 248 neurons during the switching task (interleaved blocks of recognition and recall). Task context had a profound influence on neural selectivity for objects. During the recall task, the first object was encoded more strongly than the second object, while during the recognition task, the second object was encoded more strongly. In addition, most of the neurons encoded both the task and the objects, evidence for a single

Abstract—Persistent elevated neuronal activity has been identified as the neuronal correlate of working memory. It is generally assumed in the literature and in computational and theoretical models of working memory that memory-cell activity is stable and replicable; however, this assumption may be an artifact of the averaging of data collected across trials, and needs experimental verification. In this study, we introduce a classification scheme to characterize the firing frequency trends of cells recorded from the cortex of monkeys during performance of working memory tasks. We examine the frequency statistics and variability of firing during baseline and memory periods. We also study the behavior of cells on individual trials and across trials, and explore the stability of cellular firing during the memory period. We find that cells from different firing-trend classes possess markedly different statistics. We also find that individual cells show substantial variability in their firing behavior across trials, and that firing

Abstract—Work with individuals with lesions to specific brain regions has long been used to test or even generate theories regarding the neural systems that support specific cognitive processes. Work with individuals who have neuropsychiatric disorders that also involve neurobiological disturbances may be able to play a similar role in theory testing and building. For example, schizophrenia is a psychiatric disorder thought to involve a range of neurobiological disturbances. Further, individuals with schizophrenia are known to suffer from deficits in working memory, meaning that examining the work on the neurobiology of working memory deficits in schizophrenia may help to further our understanding of the cognitive neuroscience of working memory. This article discusses the pros and cons of extrapolating from work in schizophrenia to models of healthy working memory function, and reviews the literature on working memory function in schizophrenia in relationship to existing human and non-human primate models of the cognitive neuroscience of working memory. © 2005

Prefrontal-hippocampal dynamics involved in learning regularities across episodes Using functional magnetic resonance imaging, the neural correlates of context-specific memories and invariant memories about regularities across episodes were investigated. Volunteers had to learn conjunctions between objects and positions. In an invariant learning condition, positions were held constant, enabling subjects to learn regularities across trials. By contrast, in a context-specific condition object--position conjunctions were trial unique. Performance increase in the invariant learning condition was paralleled by a learningrelated increase of inferior frontal gyrus activation and ventral striatal activation and a decrease of hippocampus activation. Conversely, in the context-specific condition hippocampal activation was constant across trials. We argue that the learning-related hippocampal activation pattern might be due to reduced relational binding requirements once regularities are extracted. Furthermore, we propose that the learning-related prefrontal modulation reflects the requirement to extract and maintain regularities across trials and the adjustment of object--position conjunctions on the basis of the extracted knowledge. Finally, our data suggest that the ventral striatum encodes the increased predictability of spatial features as a function of learning. Taken together, these results indicate a transition of the relative roles of distinct brain regions during learning regularities across multiple episodes: regularity learning is characterized by a shift from a hippocampal to a prefrontal--striatal brain system.

phenomena observed in unit recordings from awake animals, including match suppression, non-match enhancement, and non-match suppression. Key words: delayed match to sample; delayed non-match; stellate cells; pyramidal cells; medial entorhinal cortex; afterhyperpolarization; working memory; biophysical modeling; computer simulation; nonspecific cationic current I NCM Lesions of the entorhinal and perirhinal cortices impair performance in delayed non-match to sample (DNMS) tasks in both non-human primates (Zola-Morgan et al., 1993; Leonard et al., 1995) and rats (Otto and Eichenbaum, 1992). In delayed nonmatch to sample tasks, stimuli are presented sequentially, and animals must respond to a particular stimulus if that stimulus does not match the previously presented stimulus. The role of the entorhinal cortex in these tasks may involve activation of muscarinic cholinergic receptors, because performance in delayed matching tasks is impaired by systemic injections of muscarinic choline

Introduction Comparing and contrasting the neural properties of different brain regions can yield important insight into their respective contributions and, hence, the neural circuitry underlying a given function. Take, for example, perceptual categorization, a process fundamental for normal cognition because it gives meaning to our sensory environment. Several recent studies have reported neuronal correlates of visual categories in two interconnected cortical areas involved in visual recognition, memory, and other visual functions: the inferior temporal cortex (ITC) and the prefrontal cortex (PFC) (Vogels, 1999; Freedman et al., 2001, 2002; Nieder et al., 2002; Sigala and Logothetis, 2002). However, the respective roles of these and other brain areas in categorization remain essentially unknown. The PFC and the ITC have been studied by different investigators using different behavioral paradigms, different stimuli, etc., which are confounding factors that render comparisons between t

Intelligent organisms are capable of tracking objects even when they temporarily disappear from sight, a cognitive capacity commonly referred to as visual working memory (VWM). The neural basis of VWM has been the subject of significant scientific debate, with recent work focusing on the relative roles of posterior visual areas, such as the inferior temporal cortex (ITC), and the prefrontal cortex. Here we reexamined the contribution of ITC to VWM by recording from highly selective individual ITC neurons as monkeys engaged in multiple versions of an occlusion-based memory task. As expected, we found strong evidence for a role of ITC in stimulus encoding. We also found that almost half of these selective cells showed stimulus-selective delay period modulation, with a small but significant fraction exhibiting differential responses even in the presence of simultaneously visible interfering information. When we combined the informational content of multiple neurons, we found that the accuracy with which we could decode memory content increased drastically. The memory epoch analyses suggest that behaviorally relevant visual memories were reinstated in ITC. Furthermore, we observed a population-wide enhancement of neuronal response to a match stimulus compared with the same stimulus presented as a nonmatch. The single-cell enhancement preceded any match effects identified in the local field potential, leading us to speculate that enhancement is the result of neural processing local to ITC. Moreover, match enhancement was only later followed by the more commonly observed match suppression. Altogether, the data support the hypothesis that, when a stimulus is held in memory, ITC neurons are actively biased in favor of task-relevant visual representations and that this bias can immediately impact subsequent recognition events.