"The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatto)": Correction to Bussey et al (2001).

Reports an error in "The role of ventral and orbital prefrontal cortex in conditional visuomotor learning and strategy use in rhesus monkeys (Macaca mulatta)." by Timothy J. Bussey, Steven P. Wise and Elisabeth A. Murray (Behavioral Neuroscience, 2001[Oct], Vol 115[5], 971-982). In Figure 1 (p. 974), the extent of the intended lesions in the sections 32 and 28 mm from the interaural plane was misprinted. The correctly printed figure is shown in the erratum. (The following abstract of the original article appeared in record 2001-18882-001.) Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of visuomotor associations in 50 trials or less, within single test sessions. After bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost the ability to learn these associations within a session, although they could learn them when given several daily sessions. Thus, relatively slow, across-session visuomotor learning depends on neither the ventral nor orbital prefrontal cortex, but rapid, within-session learning does. The ablations also eliminated at least 2 response strategies, repeat-stay and lose-shift, which might account, in part, for the deficit in rapid learning. The deficit is unlikely to result from a failure of visual discriminative ability or working memory: The monkeys could discriminate similar stimulus material within a session, and reducing the working memory load did not improve within-session learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of ventral and orbital prefrontal cortex with inferotemporal cortex in conditional visuomotor learning.

Five rhesus monkeys (Macaca mulatta) were trained to learn novel conditional visuomotor associations, to perform this task with familiar stimuli, and to perform a visual matching-to-sample task with the same familiar stimuli. Removal of the orbital and ventral prefrontal cortex (PFv+o) in 1 hemisphere and inferotemporal cortex (IT) in the other, thus completing a surgical disconnection of these 2 regions, yielded an impairment on all 3 tasks. Addition of a premotor cortex lesion to the hemisphere containing the PFv+o lesion did not worsen the impairments. The results indicate that PFv+o interacts with IT in both the learning and retention of conditional visuomotor associations. In addition to those associations, which might be considered lower order rules for choosing a response, frontotemporal interaction also appears to be important for higher order rules, such as those involved in the matching task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairment in object-in-place scene learning after uncinate fascicle section in macaque monkeys.

Three previous experiments have shown that a disconnection of frontal cortex from inferior temporal cortex in monkeys impairs a variety of visual learning tasks but leaves concurrent object discrimination learning intact. In the present experiment, three monkeys were trained on an object-in-place task where concurrent object discrimination learning took place within unique background scenes. After surgery to transect the uncinate fascicle, the monosynaptic route between prefrontal cortex and inferior temporal cortex, all three monkeys showed an impairment relative to their preoperative performance. Combined with previously reported impairments after uncinate fascicle transection, the interaction between frontal cortex and inferotemporal cortex is likely to be important in discrimination learning in background scenes because learning depends on associating the visual elements of a scene together with the appropriate choice object. This result adds to recent evidence showing that tasks such as object-in-place learning and conditional learning are impaired after disconnection of frontal cortex from inferior temporal cortex because those tasks require the representation of temporally extended events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the hippocampus plus subjacent cortex but not amygdala in visuomotor conditional learning in Rhesus monkeys.

Rhesus monkeys were trained to learn a large series of visuomotor conditional associations, each involving the arbitrary coupling of a visual stimulus with 1 of 3 potentially correct forelimb movements. The monkeys then received bilateral aspiration lesions of either the amygdala plus subjacent cortex or the hippocampus plus subjacent cortex. Hippocampal but not amygdala removals significantly retarded the learning of new visuomotor associations. Neither lesion affected retention. The findings argue against a general role for the amygdala in associating information across modalities, construed broadly to include motor information. By contrast, the finding that the hippocampal formation and its subjacent cortex play a role in learning new sensorimotor associations supports the view that this region participates in the long-term storage of associative information or in the recall of recently acquired information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Working and long-term memory deficits in schizophrenia: Is there a common prefrontal mechanism?

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural activity in the primate prefrontal cortex during associative learning

The prefrontal (PF) cortex has been implicated in the remarkable ability of primates to form and rearrange arbitrary associations rapidly. This ability was studied in two monkeys, using a task that required them to learn to make specific saccades in response to particular cues and then repeatedly reverse these responses. We found that the activity of individual PF neurons represented both the cues and the associated responses, perhaps providing a neural substrate for their association. Furthermore, during learning, neural activity conveyed the direction of the animals' impending responses progressively earlier within each successive trial. The final level of activity just before the response, however, was unaffected by learning. These results suggest a role for the PF cortex in learning arbitrary cue-response associations, an ability critical for complex behavior.     

Executive Functioning, Memory, and Learning in Phenylketonuria.

The executive deficit hypothesis of treated phenylketonuria (PKU) suggests that dopaminergic depletion in the lateral prefrontal cortex leads to selective executive impairment. This was examined by comparing adults with PKU on a lifelong diet with a matched healthy control group. Those with PKU were impaired on selective and sustained attention, working memory (Self-Ordered Pointing), and letter fluency. However, they failed to show differential sensitivity to increased cognitive load on the attentional and working memory tasks, and they did not differ significantly on the remaining executive tasks (rule finding, inhibition, and multitasking). Nor did they differ significantly on recall or recognition memory. Overall, the findings provided little support for the executive deficit hypothesis. A possible explanation in terms of slowed information processing speed is explored. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory": Correction to Ragozzino et al. (1998).

Reports an error in "Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory" by Michael E. Ragozzino, Spencer Adams and Raymond P. Kesner (Behavioral Neuroscience, 1998[Apr], Vol 112[2], 293-303). Figure 1 (page 295) and Figure 4 (page 299) were printed incorrectly. The corrected figure pages and corresponding captions are provided in the erratum. (The following abstract of the original article appeared in record 1998-01023-003.) The present study examined the effects of quinolinic acid lesions of the dorsal anterior cingulate and prelimbic-infralimbic cortices on spatial working memory and spatial discrimination using go/no-go procedures. All testing occurred in a 12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms for a cereal reward. Three or 4 arms were presented for a 2nd time in a session, which did not result in a reward. In a spatial discrimination task, rats had successive access to 2 different arms. One arm always contained a reward, and the other never contained a reward. Prelimbic-infralimbic lesions impaired spatial working memory but only produced a transient spatial discrimination deficit. Dorsal anterior cingulate lesions did not induce a deficit in either task. These findings suggest that the prelimbic-infralimbic cortices, but not the anterior cingulate cortex, are important in spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of Perirhinal Cortex in Visual Discrimination Learning for Visual Secondary Reinforcement in Rats.

Perirhinal cortex in monkeys has been thought to be involved in visual associative learning. The authors examined rats' ability to make associations between visual stimuli in a visual secondary reinforcement task. Rats learned 2-choice visual discriminations for secondary visual reinforcement. They showed significant learning of discriminations before any primary reinforcement. Following bilateral perirhinal cortex lesions, rats continued to learn visual discriminations for visual secondary reinforcement at the same rate as before surgery. Thus, this study does not support a critical role of perirhinal cortex in learning for visual secondary reinforcement. Contrasting this result with other positive results, the authors suggest that the role of perirhinal cortex is in "within-object" associations and that it plays a much lesser role in stimulus-stimulus associations between objects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating Self-Generated Information: Anterior Prefrontal Contributions to Human Cognition.

The anterior or rostrolateral prefrontal cortex (RLPFC) is frequently recruited during complex cognitive tasks across a wide range of domains, including reasoning, long-term memory retrieval, and working memory. The authors report an event-related functional MRI study, indicating that the RLPFC is specifically involved in the evaluation of internally generated information--or information that cannot be readily perceived from the external environment but has to be inferred or self-generated. The findings are consistent with a hierarchical model of lateral prefrontal organization, with RLPFC contributing only at the highest orders of cognitive transformations. This characterization of RLPFC function may help explain seemingly disparate findings across multiple cognitive domains and could provide a unified account of this region's contribution to human cognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the rat perirhinal cortex spare the acquisition of a complex configural visual discrimination yet impair object recognition.

Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cognitive and neural architecture of sequence representation.

The authors theorize that 2 neurocognitive sequence-learning systems can be distinguished in serial reaction time experiments, one dorsal (parietal and supplementary motor cortex) and the other ventral (temporal and lateral prefrontal cortex). Dorsal system learning is implicit and associates noncategorized stimuli within dimensional modules. Ventral system learning can be implicit or explicit. It also allows associating events across dimensions and therefore is the basis of cross-task integration or interference, depending on degree of cross-task correlation of signals. Accordingly, lack of correlation rather than limited capacity is responsible for dual-task effects on learning. The theory is relevant to issues of attentional effects on learning; the representational basis of complex, sequential skills; hippocampal- versus basal ganglia-based learning; procedural versus declarative memory; and implicit versus explicit memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Prefrontal cortex and rule abstraction: Where and whether? Theoretical comment on Moore et al. (2009).

The primate dorsolateral prefrontal cortex is implicated in diverse aspects of behavioral regulation, cognitive control, and memory. However, direct neuropsychological evidence supporting a requirement of this area in functions other than spatial working memory has been scarce. T. L. Moore, S. P. Schettler, R. J. Killiany, D. L. Rosene, and M. B. Moss (see record 2009-04037-001) have shown, for the first time, that lesions of dorsolateral prefrontal cortex in the rhesus monkey (including areas 9 and 46) substantially impair performance in a test of executive function modeled on the Wisconsin Card Sorting Task. The pattern of impairment is consistent with a role for dorsolateral prefrontal areas in rule abstraction but may relate to a role for this area in rule maintenance as well. Interestingly, monkeys with dorsolateral prefrontal lesions do not appear to perseverate in their use of particular rules in the task, different from the common impairment associated with frontal lobe damage in humans. These findings indicate that dorsolateral prefrontal cortex is necessary for some aspects of rule-guided behavior in the primate brain and help illuminate the involvement of different prefrontal areas in different aspects of executive function and rule-guided behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential involvement of the dorsal anterior cingulate and prelimbic–infralimbic areas of the rodent prefrontal cortex in spatial working memory.

[Correction Notice: An erratum for this article was reported in Vol 112(4) of Behavioral Neuroscience (see record 2008-09590-001). Figure 1 (page 295) and Figure 4 (page 299) were printed incorrectly. The corrected figure pages and corresponding captions are provided in the erratum.] The present study examined the effects of quinolinic acid lesions of the dorsal anterior cingulate and prelimbic–infralimbic cortices on spatial working memory and spatial discrimination using go/no-go procedures. All testing occurred in a 12-arm radial maze. In a working memory task, rats were allowed to enter 12 arms for a cereal reward. Three or 4 arms were presented for a 2nd time in a session, which did not result in a reward. In a spatial discrimination task, rats had successive access to 2 different arms. One arm always contained a reward, and the other never contained a reward. Prelimbic–infralimbic lesions impaired spatial working memory but only produced a transient spatial discrimination deficit. Dorsal anterior cingulate lesions did not induce a deficit in either task. These findings suggest that the prelimbic–infralimbic cortices, but not the anterior cingulate cortex, are important in spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain difference in the effect of infralimbic cortex lesions on fear extinction in rats.

The infralimbic division of the medial prefrontal cortex (IL) has been implicated in the consolidation and retention of extinction memories. However, the effects of IL lesions on the retention of extinction memory are inconsistent. In the present experiments, we examined whether rat strain influences the effects of IL lesions on extinction. In Experiment 1, Sprague-Dawley (SD) or Long-Evans (LE) rats received a standard auditory fear conditioning procedure, which was followed by an extinction session; freezing served as the index of conditional fear. Our results reveal that focal IL lesions impair the retention of extinction in SD, but not LE rats. In addition to the strain difference in sensitivity to IL lesions, LE rats exhibited significantly higher levels of contextual fear before the outset of extinction training than SD rats. In a second experiment we thus examined whether contextual fear influenced the sensitivity of extinction to IL lesions in LE rats. LE rats received the same conditioning as in Experiment 1, and then were either merely exposed to a novel context or administered unsignaled shocks in that context, followed by extinction and test sessions. Our results reveal that LE rats with IL lesions showed normal extinction regardless of the levels of contextual fear manifest before extinction. Thus, we conclude that rat strain is an important variable that influences the role of infralimbic cortex in fear extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive preconditions for responses to fairness: An object retrieval test of inhibitory control in capuchin monkeys (Cebus apella).

The authors explore the evolution of one cognitive mechanism required for altruistic behavior: the capacity to inhibit prepotent responses. Specifically, the authors used an object retrieval task to investigate whether capuchins (Cebus apella) can inhibit a prepotent strategy of reaching directly for a food reward. Success in this task varies across species and across development, but is also known to depend critically on the maturity of dorsolateral prefrontal cortex, the cortical area implicated in rejecting small payoffs in an Ultimatum Game. Capuchins easily inhibit the tendency to reach directly for food in the object retrieval task, successfully employing an alternative reaching strategy even in the first session of performance. This contrasts with the performance of closely related tamarin monkeys, who performed less well despite extensive training. These results provide the first evidence that capuchins likely exhibit human-like inhibitory control in tasks previously linked to the function of the dorsolateral prefrontal cortex, such as the Ultimatum Game. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Probabilistic contingency learning with limbic or prefrontal damage.

A fundamental capacity of the human brain is to learn relations (contingencies) between environmental stimuli and the consequences of their occurrence. Some contingencies are probabilistic; that is, they predict an event in some situations but not in all. Animal studies suggest that damage to limbic structures or the prefrontal cortex may disturb probabilistic learning. The authors studied the learning of probabilistic contingencies in amnesic patients with limbic lesions, patients with prefrontal cortex damage, and healthy controls. Across 120 trials, participants learned contingent relations between spatial sequences and a button press. Amnesic patients had learning comparable to that of control subjects but failed to indicate what they had learned. Across the last 60 trials, amnesic patients and control subjects learned to avoid a noncontingent choice better than frontal patients. These results indicate that probabilistic learning does not depend on the brain structures supporting declarative memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decision making and reward in frontal cortex: Complementary evidence from neurophysiological and neuropsychological studies.

Patients with damage to the prefrontal cortex (PFC)—especially the ventral and medial parts of PFC—often show a marked inability to make choices that meet their needs and goals. These decision-making impairments often reflect both a deficit in learning concerning the consequences of a choice, as well as deficits in the ability to adapt future choices based on experienced value of the current choice. Thus, areas of PFC must support some value computations that are necessary for optimal choice. However, recent frameworks of decision making have highlighted that optimal and adaptive decision making does not simply rest on a single computation, but a number of different value computations may be necessary. Using this framework as a guide, we summarize evidence from both lesion studies and single-neuron physiology for the representation of different value computations across PFC areas. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Retrieval of emotional memories.

Long-term memories are influenced by the emotion experienced during learning as well as by the emotion experienced during memory retrieval. The present article reviews the literature addressing the effects of emotion on retrieval, focusing on the cognitive and neurological mechanisms that have been revealed. The reviewed research suggests that the amygdala, in combination with the hippocampus and prefrontal cortex, plays an important role in the retrieval of memories for emotional events. The neural regions necessary for online emotional processing also influence emotional memory retrieval, perhaps through the reexperience of emotion during the retrieval process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Animal models of prefrontal-executive function.

Executive function allows us to interact with the world in a purposive, goal-directed manner. It relies on several cognitive control operations that are mediated by different regions of the prefrontal cortex. While much of our knowledge about the functional subdivisions of the prefrontal cortex comes from the systematic assessment of patients with brain damage, animal models have served as the predominant tool for investigating specific structure–function relationships within the prefrontal cortex, especially as they relate to complex executive behaviors. These studies generally involve the targeted disruption of neural circuits combined with behavioral testing using carefully designed cognitive paradigms. In this review, I will describe a broad range of such experiments conducted in rats and monkeys that together reveal the distinct contributions of dorsal, medial, and ventral prefrontal cortex to different aspects of executive function. The effects of lesions and local pharmacological manipulations have provided valuable insights into the neural underpinnings of executive function and its neurochemical modulation. Despite the challenges associated with establishing a precise homology between animal models of prefrontal function and the human brain, such models currently offer the best means to systematically investigate the cognitive building blocks of executive function. This helps define the neural circuits that lead to a range of neurological and psychiatric disorders and facilitate the development of effective therapeutic strategies to ameliorate the associated cognitive impairments. (PsycINFO Database Record (c) 2011 APA, all rights reserved)