Inter-Individual Decision-Making Differences in the Effects of Cingulate, Orbitofrontal, and Prelimbic Cortex Lesions in a Rat Gambling Task

Deficits in decision-making is a hallmark of several neuropsychiatric pathologies but is also observed in some healthy individuals that could be at risk to develop these pathologies. Poor decision-making can be revealed experimentally in humans using the Iowa gambling task, through the inability to select options that ensure long term gains over larger immediate gratification. We devised an analogous task in the rat, based on uncertainty and conflicting choices, the rat gambling task (RGT). It similarly reveals good and poor performers within a single session. Using this task, we investigated the role of three prefrontal cortical areas, the orbitofrontal, prelimbic, and cingulate cortices on decision-making, taking into account inter-individual variability in behavioral performances. Here, we show that these three distinct subregions are differentially engaged to solve the RGT. Cingulate cortex lesion mainly delayed good decision-making whereas prelimbic and orbitofrontal cortices induced different patterns of inadapted behaviors in the task, indicating varying degree of functional specialization of these three areas. Their contribution largely depended on the level of adaptability demonstrated by each individual to the constraint of the task. The inter-individual differences in the effect of prefrontal cortex area lesions on decision-making revealed in this study open new perspectives in the search for vulnerability markers to develop disorders related to executive dysfunctioning

Reinforcement Learning Approaches to Instrumental Contingency Degradation in Rats

International audienceGoal directed action involves a representation of the consequences of an action. Rats with lesions of the medial prefrontal cortex do not adapt their instrumental response in a Skinner box when food delivery becomes unrelated to lever pressing. This indicates a role for the prefrontal region in adapting to contingency changes, a form of causal learning. We attempted to model this phenomenon in a reinforcement learning framework. Behavioural sequences of normal and lesioned rats were used to feed models based on the SARSA algorithm. One model (factorized-states) focused on temporal factors, representing continuous states as vectors of decaying event traces. The second model (event sequence) emphasized sequences, representing states as n-uplets of events. The values of state-action pairs were incorporated into a softmax policy to derive predicted action probabilities and adjust model parameters. Both models revealed a number of discrepancies between predicted and actual behaviour, emphasising changes in magazine visits rather that lever presses. The models also did not reproduce the differential adaptation of normal and prefrontal lesioned rats to contingency degradation. These data suggest that temporal difference learning models fail to capture causal relationships involved in the adaptation to contingency changes

Antimony and bismuth oxide cluster ions

The formation of charged antimony and bismuth oxide clusters in a pulsed arc cluster ion source (PACIS) has been studied with time-of-Ñight mass spectrometric techniques. We compare series of antimony and bismuth oxide cluster anions with their known cationic counterparts. The anionic series and (M 2 O 3 ) n MO 2h ave been predicted proceeding from the known cationic series and n Ob y adding O2~and have been experimentally established. All these series contain the metal atoms (M \ Sb or Bi) in the formal oxidation state ]3. However, only in the case of antimony, oxygen rich oxide clusters appear, that can be explained with a gradual transition in the oxidation number from ]3 to ]5 of single antimony atoms in the cluster. To estimate the inÑuence of the special oxide formation conditions comparative investigations with the PACIS and a laser vaporisation cluster source have been carried out for bismuth oxide cations. The similar oxide cluster distributions at comparable oxygen availability display clearly that the special thermodynamical stability of the discussed magic clusters is the signiÐcant driving force for their formation

Regulation of reinforcement learning parameters captures long-term changes in rat behaviour

In uncertain environments in which resources fluctuate continuously, animals must permanently decide whether to stabilise learning and exploit what they currently believe to be their best option, or instead explore potential alternatives and learn fast from new observations. While such a trade-off has been extensively studied in pretrained animals facing non-stationary decision-making tasks, it is yet unknown how they progressively tune it while learning the task structure during pretraining. Here, we compared the ability of different computational models to account for long-term changes in the behaviour of 24 rats while they learned to choose a rewarded lever in a three-armed bandit task across 24 days of pretraining. We found that the day-by-day evolution of rat performance and win-shift tendency revealed a progressive stabilisation of the way they regulated reinforcement learning parameters. We successfully captured these behavioural adaptations using a meta-learning model in which either the learning rate or the inverse temperature was controlled by the average reward rate

Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviour

The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a ‘forced choice’ task, various parameter manipulations and an omission schedule version of the task. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re-stabilized on the standard version of the task and challenged with increasing doses of d-amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core- nor shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d-amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose-dependent effect of d-amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d-amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences

Differentiating neural systems mediating the acquisition vs. expression of goal-directed and habitual behavioral control

Considerable behavioral data indicate that operant actions can become habitual, as demonstrated by insensitivity to changes in the action–outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with functional magnetic resonance imaging as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also showed that the inferior parietal lobule (an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency) predicted sensitivity to outcome devaluation. Finally, we revealed a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggested a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action–outcome and stimulus–response associations

Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression

<p>Abstract</p> <p>Background</p> <p>Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The neurobiological underpinnings of these conditioned responses are not well understood. Monitoring regional immediate early gene expression is a method used to assess alterations in neuronal metabolism resulting from upstream intracellular and extracellular signaling. Furthermore, assessing the expression of multiple immediate early genes offers a window onto the possible sequelae of exposure to food cues, since the function of each gene differs. We used immediate early gene and proenkephalin expression as a means of assessing food cue-elicited regional activation and alterations in functional connectivity within the forebrain.</p> <p>Results</p> <p>Contextual cues associated with palatable food elicited conditioned motor activation and corticosterone release in rats. This motivational state was associated with increased transcription of the activity-regulated genes <it>homer1a</it>, <it>arc</it>, <it>zif268</it>, <it>ngfi-b </it>and c-<it>fos </it>in corticolimbic, thalamic and hypothalamic areas and of proenkephalin within striatal regions. Furthermore, the functional connectivity elicited by food cues, as assessed by an inter-regional multigene-expression correlation method, differed substantially from that elicited by neutral cues. Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the shell towards the core. Exposure to the food-associated context also induced correlated gene expression between corticostriatal networks and the basolateral amygdala, an area critical for learning and responding to the incentive value of sensory stimuli. This increased corticostriatal-amygdalar functional connectivity was absent in the control group exposed to innocuous cues.</p> <p>Conclusion</p> <p>The results implicate correlated activity between the cortex and the striatum, especially the nucleus accumbens core and the basolateral amygdala, in the generation of a conditioned motivated state that may promote excessive food intake. The upregulation of a number of genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. As many of these genes play a role in plasticity, their upregulation within these circuits may also indicate the neuroanatomic and transcriptional correlates of extinction learning.</p