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Geoffrey Schoenbaum

Publications and source records attributed to Geoffrey Schoenbaum.

At least 19 recordsLinked to original sources
PubMed2007

Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude.

Animals prefer an immediate over a delayed reward, just as they prefer a large over a small reward. Exposure to psychostimulants causes long-lasting changes in structures critical for this behavior and might disrupt normal time-discounting performance. To test this hypothesis, we exposed rats to cocaine daily for 2 weeks (30 mg/kg, i.p.). Approximately 6 weeks later, we tested them on a variant of a time-discounting task, in which the rats responded to one of two locations to obtain reward while we independently manipulated the delay to reward and reward magnitude. Performance did not differ between cocaine-treated and saline-treated (control) rats when delay lengths and reward magnitudes were equal at the two locations. However, cocaine-treated rats were significantly more likely to shift their responding when we increased the delay or reward size asymmetrically. Furthermore, they were slower to respond and made more errors when forced to the side associated with the lower value. We conclude that previous exposure to cocaine makes choice behavior hypersensitive to differences in the time to and size of available rewards, consistent with a general effect of cocaine exposure on reward valuation mechanisms.

Animals↗
PubMed2006

Encoding of time-discounted rewards in orbitofrontal cortex is independent of value representation.

We monitored single-neuron activity in the orbitofrontal cortex of rats performing a time-discounting task in which the spatial location of the reward predicted whether the delay preceding reward delivery would be short or long. We found that rewards delivered after a short delay elicited a stronger neuronal response than those delivered after a long delay in most neurons. Activity in these neurons was not influenced by reward size when delays were held constant. This was also true for a minority of neurons that exhibited sustained increases in firing in anticipation of delayed reward. Thus, encoding of time-discounted rewards in orbitofrontal cortex is independent of the encoding of absolute reward value. These results are contrary to the proposal that orbitofrontal neurons signal the value of delayed rewards in a common currency and instead suggest alternative proposals for the role this region plays in guiding responses for delayed versus immediate rewards.

Action Potentials↗
PubMed2006

Associative encoding in posterior piriform cortex during odor discrimination and reversal learning.

Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex and basolateral amygdala (ABL). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. We recently reported that neurons in anterior piriform cortex (APC) in rats exhibited significant plasticity in their responses to odor cues during associative learning. Here, we have repeated this study, recording from neurons in posterior piriform cortex (PPC), a region of piriform cortex that receives much stronger input from ABL. If associative encoding in piriform cortex is driven by inputs from ABL, then we should see more plasticity in PPC neurons than we observed in APC. Consistent with this hypothesis, we found that PPC neurons were highly associative and appeared to be somewhat more likely than neurons recorded in APC to alter their responses to the odor cues after reversal of the odor-outcome associations in the task. Further, odor-selective PPC populations exhibited markedly different firing patterns based on the valence of the odor cue. These results suggest associative encoding in piriform cortex is represented in a topographical fashion, reflecting the stronger and more specific input from olfactory bulb concerning the sensory features of odors in anterior regions and stronger input from ABL concerning the meaning of odors in posterior regions.

Amygdala↗
PubMed2006

Prior cocaine exposure disrupts extinction of fear conditioning.

Psychostimulant exposure has been shown to cause molecular and cellular changes in prefrontal cortex. It has been hypothesized that these drug-induced changes might affect the operation of prefrontal-limbic circuits, disrupting their normal role in controlling behavior and thereby leading to compulsive drug-seeking. To test this hypothesis, we tested cocaine-treated rats in a fear conditioning, inflation, and extinction task, known to depend on medial prefrontal cortex and amygdala. Cocaine-treated rats conditioned and inflated similar to saline controls but displayed slower extinction learning. These results support the hypothesis that control processes in the medial prefrontal cortex are impaired by cocaine exposure.

Animals↗
PubMed2006

Associative encoding in anterior piriform cortex versus orbitofrontal cortex during odor discrimination and reversal learning.

Recent proposals have conceptualized piriform cortex as an association cortex, capable of integrating incoming olfactory information with descending input from higher order associative regions such as orbitofrontal cortex (OFC). If true, encoding in piriform cortex should reflect associative features prominent in these areas during associative learning involving olfactory cues. To test this hypothesis, we recorded from neurons in OFC and anatomically related parts of the anterior piriform cortex (APC) in rats, learning and reversing novel odor discriminations. Findings in OFC were similar to what we have reported previously, with nearly all the cue-selective neurons exhibiting substantial plasticity during learning and reversal. Also, many of the cue-selective neurons were originally responsive in anticipation of the outcomes early in learning, thereby providing a single-unit representation of the cue-outcome associations. Some of these features were also evident in firing activity in APC, including some plasticity across learning and reversal. However, APC neurons failed to reverse cue selectivity when the associated outcome was changed, and the cue-selective population did not include neurons that were active prior to outcome delivery. Thus, although representations in APC are substantially more associative than expected in a purely sensory region, they do appear to be somewhat more constrained by the sensory features of the odor cues than representations in downstream areas of OFC.

Animals↗
PubMed2006

Orbitofrontal cortex, decision-making and drug addiction.

The orbitofrontal cortex, as a part of prefrontal cortex, is implicated in executive function. However, within this broad region, the orbitofrontal cortex is distinguished by its unique pattern of connections with crucial subcortical associative learning nodes, such as basolateral amygdala and nucleus accumbens. By virtue of these connections, the orbitofrontal cortex is uniquely positioned to use associative information to project into the future, and to use the value of perceived or expected outcomes to guide decisions. This review will discuss recent evidence that supports this proposal and will examine evidence that loss of this signal, as the result of drug-induced changes in these brain circuits, might account for the maladaptive decision-making that characterizes drug addiction.

Animals↗
PubMed2006

Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-making.

Recent evidence has linked exposure to addictive drugs to an inability to employ information about adverse consequences, or outcomes, to control behavior. For instance, addicts and drug-experienced animals fail to adapt their behavior to avoid adverse outcomes in gambling and reversal tasks or after changes in the value of expected rewards. These deficits are similar to those caused by damage to the orbitofrontal cortex, suggesting that addictive drugs may cause long-lasting changes in the representation of outcome associations in a circuit that includes the orbitofrontal cortex. Here we test this hypothesis by recording from orbitofrontal neurons in a discrimination task in rats previously exposed to cocaine (30 mg/kg i.p. for 14 days). We found that orbitofrontal neurons recorded in cocaine-experienced rats failed to signal the adverse outcome at the time a decision was made in the task. The loss of this signal was associated with abnormal changes in response latencies on aversive trials. Furthermore, upon reversal of the cue-outcome associations, orbitofrontal neurons in cocaine-treated rats with enduring reversal impairments failed to reverse their cue-selectivity, while orbitofrontal neurons in cocaine-treated rats with normal performance showed an increase in the plasticity of cue-selective firing after reversal. These results provide direct neurophysiological evidence that exposure to cocaine can cause behaviorally relevant changes in the processing of associative information in a circuit that includes the orbitofrontal cortex.

Animals↗
PubMed2005

Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

Action Potentials↗
PubMed2005

Orbitofrontal cortex, associative learning, and expectancies.

Orbitofrontal cortex is characterized by its unique pattern of connections with subcortical areas, such as basolateral amygdala. Here we distinguish between the critical role of these areas in associative learning and the pivotal contribution of OFC to the manipulation of this information to control behavior. This contribution reflects the ability of OFC to signal the desirability of expected outcomes, which requires the integration of associative information with information concerning internal states and goals in representational memory.

Amygdala↗
PubMed2005

Rapid associative encoding in basolateral amygdala depends on connections with orbitofrontal cortex.

Certain goal-directed behaviors depend upon interactions between basolateral amygdala (ABL) and orbitofrontal cortex (OFC). Here we describe neurophysiological evidence of this cooperative function. We recorded from ABL in intact and OFC-lesioned rats during learning of odor discrimination problems and reversals. During learning, rats with ipsilateral OFC lesions exhibited a marked decline in the proportion of ABL neurons that fired differentially during cue sampling both before and after reversal and in the proportion of neurons that reversed odor preference when the odor-outcome associations were reversed. This decline appeared to reflect a loss of rapid flexibility in cue selectivity that characterized activity in intact rats. In addition, lesioned rats had fewer neurons that fired in anticipation of the predicted outcome during a delay period after responding but before outcome delivery. These findings support a role for OFC in facilitating the encoding of information about expected outcomes in ABL.

Amygdala↗
PubMed2004

Cocaine makes actions insensitive to outcomes but not extinction: implications for altered orbitofrontal-amygdalar function.

Addiction is characterized by persistent drug-seeking despite adverse consequences or outcomes. Such persistent behavior may result from drug-induced brain changes that increase the control of behavior by associations between antecedent cues and responses. However, it is equally plausible that brain changes cause a decrease in the control of behavior by the value of likely outcomes. To test whether drug exposure can cause persistent behavior, and to distinguish between these two accounts of such behavior, we tested cocaine-experienced rats in a Pavlovian 'reinforcer devaluation' task, which provides independent assessments of the control of behavior by antecedent cues and outcome representations. We found that cocaine exposure caused persistent responding in this setting a month after the last drug treatment, and that this deficit resulted from an inability to use representations of outcome value to guide behavior rather than from changes in stimulus-response learning or response inhibition.

Amygdala↗
PubMed2004

Cocaine-experienced rats exhibit learning deficits in a task sensitive to orbitofrontal cortex lesions.

Addictive drugs, such as cocaine, cause long-lasting neural changes in prefrontal cortex. It has been hypothesized that these changes affect the behavioural control mediated by orbitofrontal cortex. To test this hypothesis, rats were given injections of cocaine (30 mg/kg/d, i.p.) or vehicle for 14 days and then trained after a 2-week withdrawal period in an odor discrimination task sensitive to the effects of orbitofrontal cortex lesions. We found that cocaine-treated rats, who demonstrated long-lasting sensitization to the locomotor activating effects of cocaine, failed to show normal changes in response latency during discrimination learning and were also slower than controls to acquire serial reversals. These behavioural impairments are identical to the effects of orbitofrontal cortex lesions in this task and show that cocaine exposure in rats can cause long-lasting effects on orbitofrontal-dependent functions. Notably, these effects were not correlated with increases in locomotor activity linked to cocaine-induced psychomotor sensitization observed before or after training, suggesting that the brain changes underlying the behavioural effects in the discrimination task are different from those mediating psychomotor sensitization.

Anesthetics, Local↗
PubMed2003

Different roles for orbitofrontal cortex and basolateral amygdala in a reinforcer devaluation task.

The orbitofrontal cortex (OFC) and basolateral amygdala (BLA) are critical for using learned representations of outcomes to guide behavior. Neurophysiological findings suggest complementary roles in which the BLA acquires associations between cues and outcomes and the OFC subsequently uses them to guide behavior. Here, we have used a reinforcer devaluation paradigm to test this hypothesis. In this paradigm, rats are first trained to associate a light conditioned stimulus (CS) with a food outcome, and then the food is devalued by pairing it with illness. After this devaluation procedure, responding to the CS is assessed in a single probe session. Previously, we have shown that BLA and OFC lesions made before training do not affect the acquisition of conditioned responding but do impair the sensitivity of that responding to reinforcer devaluation. Rats with such lesions fail to exhibit the spontaneous decrease in conditioned responding to the light cue observed in controls in the probe test. Here, we have extended those findings by showing that performance in the probe test is impaired by OFC lesions made after light-food conditioning but not by BLA lesions made after that training. These findings indicate that the OFC and BLA play different roles in mediating normal goal-directed performance in this, and likely other, settings. The BLA seems critical to forming representations linking cues to the incentive properties of outcomes but not for maintaining these representations in memory, updating them with new information, or for expressing them in behavior. In contrast, the OFC seems essential for one or more of these latter processes.

Amygdala↗
PubMed2003

A systems approach to orbitofrontal cortex function: recordings in rat orbitofrontal cortex reveal interactions with different learning systems.

The recognition that certain aspects of prefrontal function can be effectively modeled in rats has led to a slow expansion of interest in rat prefrontal cortex over the past decade. One of the most promising of these model systems is the orbitofrontal cortex of the rat. Rat orbitofrontal cortex is anatomically similar to the orbital prefrontal region in primates, and this similarity is borne out by behavioral and neurophysiological findings. Here we will present data on orbitofrontal cortex function from a number of parallel studies from our laboratories that employed single unit recording techniques to probe neural encoding in rat orbitofrontal cortex and related parts of the amygdala and the hippocampal memory systems. Together, these reports and associated behavioral studies suggest that the orbitofrontal region, in both rats and primates, is specialized to integrate concrete and abstract sensory constructs with information regarding the incentive value of associated outcomes to guide or modulate behavior. To the extent that monkey prefrontal function can model certain aspects of human prefrontal function, we argue that this model can now be extended to the rat orbitofrontal cortex. In addition, we argue that the function of orbitofrontal cortex needs to be considered in terms of its interactions with other brain systems.

Action Potentials↗
PubMed2003

Lesions of nucleus accumbens disrupt learning about aversive outcomes.

Nucleus accumbens (NAcc) is critical for encoding and using information regarding the learned significance of cues predictive of reward. However, its role in processing information about cues predictive of aversive outcomes is less well studied. Here, we examined the effects of NAcc lesions in an odor-guided discrimination task in which rats use odor cues predictive of either appetitive or aversive outcomes to guide responding. Rats with sham or neurotoxic lesions of NAcc were trained on a series of two-odor discrimination problems. Performance on each problem was assessed by monitoring accuracy of choice behavior and by measuring latency to respond for fluid reinforcement after odor sampling. After acquisition of four problems, rats were trained on serial reversals of the final problem. Rats with NAcc lesions exhibited normal choice performance relative to controls on both acquisition and reversal of the discrimination problems (indeed, lesioned rats exhibited a mild facilitation on the first discrimination problem). Despite normal choice performance, however, lesioned rats failed to show normal changes in response latency during discrimination learning, particularly on trials involving the aversive outcome. These findings are consistent with a deficit in processing cue-outcome associations. These results are compared with those obtained from studies of basolateral amygdala and orbitofrontal cortex lesions in this task and suggest that NAcc integrates the motivational value of both appetitive and aversive cues to bias or modulate the vigor of subsequent responding.

Animals↗
PubMed2003

Encoding predicted outcome and acquired value in orbitofrontal cortex during cue sampling depends upon input from basolateral amygdala.

Certain goal-directed behaviors depend critically upon interactions between orbitofrontal cortex (OFC) and basolateral amygdala (ABL). Here we describe direct neurophysiological evidence of this cooperative function. We recorded from OFC in intact and ABL-lesioned rats learning odor discrimination problems. As rats learned these problems, we found that lesioned rats exhibited marked changes in the information represented in OFC during odor cue sampling. Lesioned rats had fewer cue-selective neurons in OFC after learning; the cue-selective population in lesioned rats did not include neurons that were also responsive in anticipation of the predicted outcome; and the cue-activated representations that remained in lesioned rats were less associative and more often bound to cue identity. The results provide a neural substrate for representing acquired value and features of the predicted outcome during cue sampling, disruption of which could account for deficits in goal-directed behavior after damage to this system.

Amygdala↗