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John J. Woodward - One of the best experts on this subject based on the ideXlab platform.
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ethanol inhibition of Lateral Orbitofrontal Cortex neuron excitability is mediated via dopamine d1 d5 receptor induced release of astrocytic glycine
Neuropharmacology, 2021Co-Authors: Sudarat Nimitvilairoberts, Dominic Gioia, Paula A Zamudio, John J. WoodwardAbstract:Recent findings from this laboratory demonstrate that ethanol reduces the intrinsic excitability of Orbitofrontal Cortex (OFC) neurons via activation of strychnine-sensitive glycine receptors. Although the mechanism linking ethanol to the release of glycine is currently unknown, astrocytes are a source of neurotransmitters including glycine and activation of dopamine D1-like receptors has been reported to enhance extracellular levels of glycine via a functional reversal of the astrocytic glycine transporter GlyT1. We recently reported that like ethanol, dopamine or a D1/D5 receptor agonist increases a tonic current in Lateral OFC (lOFC) neurons. Therefore, in this study, we used whole-cell patch-clamp electrophysiology to examine whether ethanol inhibition of OFC spiking involves the release of glycine from astrocytes and whether this release is dopamine receptor dependent. Ethanol, applied acutely, decreased spiking of lOFC neurons and this effect was blocked by antagonists of GlyT1, the norepinephrine transporter or D1-like but not D2-like receptors. Ethanol enhanced the tonic current of OFC neurons and occluded the effect of dopamine suggesting that ethanol and dopamine may share a common pathway. Altering astrocyte function by suppressing intracellular astrocytic calcium signaling or blocking the astrocyte-specific Kir4.1 potassium channels reduced but did not completely abolish ethanol inhibition of OFC neuron firing. However, when both astrocytic calcium signaling and Kir4.1 channels were inhibited, ethanol had no effect on firing. Ethanol inhibition was also prevented by inhibitors of phospholipase C and conventional isoforms of protein kinase C (cPKC) previously shown to block D1R-induced GlyT1 reversal and PKC inhibition of Kir4.1 channels. Finally, the membrane potential of OFC astrocytes was depolarized by bath application of a Kir4.1 blocker, a D1 agonist or ethanol and ethanol effect was blocked by a D1 antagonist. Together, these findings suggest that acute ethanol inhibits OFC neuron excitability via a D1 receptor-mediated dysregulation of astrocytic glycine transport.
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altered activity of Lateral Orbitofrontal Cortex neurons in mice following chronic intermittent ethanol exposure
eNeuro, 2021Co-Authors: Dominic Gioia, John J. WoodwardAbstract:The Lateral Orbito-Frontal Cortex (LOFC) is thought to encode information associated with consumption of rewarding substances and is essential for flexible decision making. Indeed, firing patterns of LOFC neurons are modulated following changes in reward value associated with an action outcome relationship. Damage to the LOFC impairs behavioral flexibility in humans and is associated with sub-optimal performance in reward devaluation protocols in rodents. As chronic intermittent ethanol (CIE) exposure also impairs OFC-dependent behaviors, we hypothesized that CIE exposure would alter LOFC neuronal activity during alcohol drinking, especially under conditions when the reward value of ethanol was modulated by aversive or appetitive tastants. To test this hypothesis, we monitored LOFC activity using GCaMP6f fiber photometry in mice receiving acute injections of ethanol and in those trained in operant ethanol self-administration. In naive mice, an acute injection of ethanol caused a dose-dependent decrease in the frequency but not amplitude of GCaMP6f transients. In operant studies, mice were trained on an fixed-ratio one schedule of reinforcement and were then separated into CIE or Air groups. Following four cycles of CIE exposure, GCaMP6f activity was recorded during self-administration of alcohol, alcohol + quinine (aversive), or alcohol + sucrose (appetitive) solutions. LOFC neurons showed discrete patterns of activity surrounding lever presses and surrounding drinking bouts. Responding for and consumption of ethanol was greatly enhanced by CIE exposure, was aversion resistant, and was associated with signs of LOFC hyperexcitability. CIE exposed mice also showed altered patterns of LOFC activity that varied with the ethanol solution consumed.Significance Statement: These studies demonstrate that, in intact mice, LOFC neurons are acutely inhibited by alcohol and become hyperexcitable following CIE exposure. Furthermore, we report that unique patterns of LOFC neuronal activity occur during alcohol seeking and consumption. Interestingly, these patterns of activity are modulated following CIE exposure, particularly when the rewarding properties of the alcohol solution are modulated through adulterations with quinine (aversive) or sucrose (appetitive). Conversely, control animals have considerably more stable patterns of LOFC activity following exposure to air. These unique effects of CIE exposure on LOFC activity likely contribute to the development of excessive alcohol consumption and behavioral inflexibility that are associated with the onset of alcohol dependence.
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sex dependent differences in ethanol inhibition of mouse Lateral Orbitofrontal Cortex neurons
Addiction Biology, 2020Co-Authors: Sudarat Nimitvilai, Marcelo F Lopez, John J. WoodwardAbstract:Biological differences between males and females likely influence responses to alcohol and the propensity to engage in excessive drinking. In both humans and rodents, females escalate alcohol use and develop addiction-like behaviors faster than males, while males exhibit more severe withdrawal symptoms during abstinence. The mechanisms underlying these differences are not yet known but may reflect fundamental differences in the ethanol sensitivity of neurons in reward and control areas of the brain. To address this question, we recorded current-evoked spiking of Lateral Orbitofrontal Cortex (lOFC) neurons in male and female C57BL/6J mice following acute and chronic exposure to ethanol. Ethanol (11-66 mM) reduced firing of lOFC neurons but produced less inhibition in neurons from female mice. As previously reported for male mice, the glycine receptor blocker strychnine blocked ethanol inhibition of spiking of lOFC neurons from female mice and prevented the ethanol-induced increase in tonic current. Following chronic intermittent ethanol (CIE) exposure, current-evoked spiking of lOFC neurons was significantly enhanced with a greater effect observed in males. After CIE treatment, acute ethanol had no effect on spiking in neurons from male mice, while it produced a slight but significant decrease in firing in females. Finally, like male mice, the inhibitory effect of the glycine transport inhibitor sarcosine was blunted in CIE-exposed female mice. Together, these results suggest that while lOFC neurons in male and female mice are similarly affected by ethanol, there are significant differences in sensitivity that may contribute to differences in alcohol actions between males and females.
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effects of monoamines on the intrinsic excitability of Lateral Orbitofrontal Cortex neurons in alcohol dependent and non dependent female mice
Neuropharmacology, 2018Co-Authors: Sudarat Nimitvilai, Marcelo F Lopez, John J. WoodwardAbstract:Changes in brain reward and control systems of frontal cortical areas including the Orbitofrontal Cortex (OFC) are associated with alcohol use disorders (AUD). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including AUDs. Recent findings from this laboratory demonstrate that D2, α2-adrenergic and 5HT1A receptors all decrease the intrinsic excitability of Lateral OFC (lOFC) neurons in naive male mice and that this effect is lost in mice exposed to repeated cycles of chronic intermittent ethanol (CIE) vapor. As biological sex differences may influence an individual's response to alcohol and contribute to the propensity to engage in addictive behaviors, we examined whether monoamines have similar effects on lOFC neurons in control and CIE exposed female mice. Dopamine, norepinephrine and serotonin all decreased spiking of lOFC neurons in naive females via activation of Giα-coupled D2, α2-adrenergic and 5HT1A receptors, respectively. Firing was also inhibited by the direct GIRK channel activator ML297, while blocking these channels with barium eliminated the inhibitory actions of monoamines. Following CIE treatment, evoked spiking of lOFC neurons from female mice was significantly enhanced and monoamines and ML297 no longer inhibited firing. Unlike in male mice, the enhanced firing of neurons from CIE exposed female mice was not associated with changes in the after-hyperpolarization and the small-conductance potassium channel blocker apamin had no effect on current-evoked tail currents from either control or CIE exposed female mice. These results suggest that while CIE exposure alters monoamine regulation of OFC neuron firing similarly in males and female mice, there are sex-dependent differences in processes that regulate the intrinsic excitability of these neurons.
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inactivation of the Lateral Orbitofrontal Cortex increases drinking in ethanol dependent but not non dependent mice
Neuropharmacology, 2016Co-Authors: Carolina Den R Hartog, Sudarat Nimitvilai, Paula Zamudiobulcock, Meghin J Gilstrap, Bethany Eaton, Hleb Fedarovich, Andrew Motts, John J. WoodwardAbstract:Long-term consumption of ethanol affects cortical areas that are important for learning and memory, cognition, and decision-making. Deficits in cortical function may contribute to alcohol-abuse disorders by impeding an individual's ability to control drinking. Previous studies from this laboratory show that acute ethanol reduces activity of Lateral Orbitofrontal Cortex (LOFC) neurons while chronic exposure impairs LOFC-dependent reversal learning and induces changes in LOFC excitability. Despite these findings, the role of LOFC neurons in ethanol consumption is unknown. To address this issue, we examined ethanol drinking in adult C57Bl/6J mice that received an excitotoxic lesion or viral injection of the inhibitory DREADD (designer receptor exclusively activated by designer drug) into the LOFC. No differences in ethanol consumption were observed between sham and lesioned mice during access to increasing concentrations of ethanol (3-40%) every other day for 7 weeks. Adulterating the ethanol solution with saccharin (0.2%) or quinine (0.06 mM) enhanced or inhibited, respectively, consumption of the 40% ethanol solution similarly in both groups. Using a chronic intermittent ethanol (CIE) vapor exposure model that produces dependence, we found no difference in baseline drinking between sham and lesioned mice prior to vapor treatments. CIE enhanced drinking in both groups as compared to air-treated animals and CIE treated lesioned mice showed an additional increase in ethanol drinking as compared to CIE sham controls. This effect persisted during the first week when quinine was added to the ethanol solution but consumption decreased to control levels in CIE lesioned mice in the following 2 weeks. In viral injected mice, baseline drinking was not altered by expression of the inhibitory DREADD receptor and repeated cycles of CIE exposure enhanced drinking in DREADD and virus control groups. Consistent with the lesion study, treatment with clozapine-N-oxide (CNO) further enhanced consumption only in CIE exposed DREADD mice with no change in air-treated mice. These results suggest that the LOFC is not critical for the initiation and maintenance of ethanol drinking in non-dependent mice, but may regulate the escalated drinking observed during dependence.
Edmund T Rolls - One of the best experts on this subject based on the ideXlab platform.
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reward versus nonreward sensitivity of the medial versus Lateral Orbitofrontal Cortex relates to the severity of depressive symptoms
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2021Co-Authors: Chao Xie, Trevor W Robbins, Wei Cheng, Edmund T Rolls, Jie Zhang, Tianye Jia, Barbara J Sahakian, Zhaowen Liu, Qiang Luo, He WangAbstract:Abstract Background The Orbitofrontal Cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms. Methods Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14. Results The medial OFC exhibited graded activation increases to reward, and the Lateral OFC had graded activation increases to nonreward. In this general population, the medial and Lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the Lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the Lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003). Conclusions Activations in the Lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.
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functional connectivity of the Orbitofrontal Cortex anterior cingulate Cortex and inferior frontal gyrus in humans
Cortex, 2020Co-Authors: Jingnan Du, Weikang Gong, Yu Li, Wei Cheng, Edmund T Rolls, Jianfeng FengAbstract:Abstract Parcellation of the Orbitofrontal Cortex, anterior cingulate Cortex, and inferior frontal gyrus based on their functional connectivity with the whole brain in resting state fMRI with 654 participants was performed to investigate how these regions with different functions in reward, emotion and their disorders are functionally connected to each other and to the whole brain. The human medial and Lateral Orbitofrontal Cortex, the ventromedial prefrontal Cortex, the anterior cingulate Cortex, and the right and left inferior frontal gyrus have different functional connectivity with other brain areas and with each other; and each of these regions has several parcels with different functional connectivity with other brain areas. In terms of functional connectivity, the Lateral Orbitofrontal Cortex extends especially on the right into the orbital part of the inferior frontal gyrus and provides connectivity with premotor cortical areas. The Orbitofrontal Cortex, especially the Lateral Orbitofrontal Cortex, has connectivity not only with language-related areas in the inferior frontal gyrus (Broca's area), but also with the angular and supramarginal gyri. In this context, whereas the connectivity of the Orbitofrontal Cortex, ventromedial prefrontal Cortex, and anterior cingulate Cortex is symmetrical, the connectivity of the inferior frontal gyrus triangular and opercular parts is asymmetrical for the right and the left hemispheres. These findings have implications for understanding the neural bases of human emotion and decision-making, and for their disorders including depression.
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functional connectivity of the precuneus in unmedicated patients with depression
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2018Co-Authors: Wei Cheng, Deyu Yang, Hongtao Ruan, Jie Meng, Edmund T Rolls, Libo Zhao, Jianfeng FengAbstract:Abstract Background The precuneus has connectivity with brain systems implicated in depression. Methods We performed the first fully voxel-level resting-state functional connectivity (FC) neuroimaging analysis of depression of the precuneus, with 282 patients with major depressive disorder and 254 control subjects. Results In 125 unmedicated patients, voxels in the precuneus had significantly increased FC with the Lateral Orbitofrontal Cortex, a region implicated in nonreward that is thereby implicated in depression. FC was also increased in depression between the precuneus and the dorsoLateral prefrontal Cortex, temporal Cortex, and angular and supramarginal areas. In patients receiving medication, the FC between the Lateral Orbitofrontal Cortex and precuneus was decreased back toward that in the control subjects. In the 254 control subjects, parcellation revealed superior anterior, superior posterior, and inferior subdivisions, with the inferior subdivision having high connectivity with the posterior cingulate Cortex, parahippocampal gyrus, angular gyrus, and prefrontal Cortex. It was the ventral subdivision of the precuneus that had increased connectivity in depression with the Lateral Orbitofrontal Cortex and adjoining inferior frontal gyrus. Conclusions The findings support the theory that the system in the Lateral Orbitofrontal Cortex implicated in the response to nonreceipt of expected rewards has increased effects on areas in which the self is represented, such as the precuneus. This may result in low self-esteem in depression. The increased connectivity of the precuneus with the prefrontal Cortex short-term memory system may contribute to the rumination about low self-esteem in depression. These findings provide evidence that a target to ameliorate depression is the Lateral Orbitofrontal Cortex.
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increased functional connectivity of the posterior cingulate Cortex with the Lateral Orbitofrontal Cortex in depression
Translational Psychiatry, 2018Co-Authors: Wei Cheng, Edmund T Rolls, Jiang Qiu, Xiongfei Xie, Dongtao Wei, Chuchung Huang, Albert C Yang, Shihjen Tsai, Jie MengAbstract:To analyze the functioning of the posterior cingulate Cortex (PCC) in depression, we performed the first fully voxel-level resting state functional-connectivity neuroimaging analysis of depression of the PCC, with 336 patients with major depressive disorder and 350 controls. Voxels in the PCC had significantly increased functional connectivity with the Lateral Orbitofrontal Cortex, a region implicated in non-reward and which is thereby implicated in depression. In patients receiving medication, the functional connectivity between the Lateral Orbitofrontal Cortex and PCC was decreased back towards that in the controls. In the 350 controls, it was shown that the PCC has high functional connectivity with the parahippocampal regions which are involved in memory. The findings support the theory that the non-reward system in the Lateral Orbitofrontal Cortex has increased effects on memory systems, which contribute to the rumination about sad memories and events in depression. These new findings provide evidence that a key target to ameliorate depression is the Lateral Orbitofrontal Cortex.
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Medial reward and Lateral non-reward Orbitofrontal Cortex circuits change in opposite directions in depression
Brain, 2016Co-Authors: Wei Cheng, Edmund T Rolls, Jiang Qiu, Chuchung Huang, Wei Liu, Yanqing Tang, Xinfa Wang, Jie Zhang, Wei Lin, Li-rong ZhengAbstract:The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial Orbitofrontal Cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal Cortex Brodmann area 36 and entorhinal Cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial Orbitofrontal Cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The Lateral Orbitofrontal Cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the Lateral Orbitofrontal Cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual Cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the Lateral Orbitofrontal Cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the Lateral Orbitofrontal Cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the Orbitofrontal Cortex in emotion helps to provide new insight into the brain changes related to depression.
Geoffrey Schoenbaum - One of the best experts on this subject based on the ideXlab platform.
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processing in Lateral Orbitofrontal Cortex is required to estimate subjective preference during initial but not established economic choice
Neuron, 2020Co-Authors: Matthew P H Gardner, Jessica C Conroy, Davied Sanchez, Andrew M Wikenheiser, Jingfeng Zhou, Geoffrey SchoenbaumAbstract:The Orbitofrontal Cortex (OFC) is proposed to be critical to economic decision making. Yet one can inactivate OFC without affecting well-practiced choices. One possible explanation of this lack of effect is that well-practiced decisions are codified into habits or configural-based policies not normally thought to require OFC. Here, we tested this idea by training rats to choose between different pellet pairs across a set of standard offers and then inactivating OFC subregions during choices between novel offers of previously experienced pairs or between novel pairs of previously experienced pellets. Contrary to expectations, controls performed as well on novel as experienced offers yet had difficulty initially estimating their subjective preference on novel pairs, difficulty exacerbated by Lateral OFC inactivation. This pattern of results indicates that established economic choice reflects the use of an underlying model or goods space and that Lateral OFC is only required for normal behavior when the established framework must incorporate new information.
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Lateral Orbitofrontal inactivation dissociates devaluation sensitive behavior and economic choice
Neuron, 2017Co-Authors: Matthew P H Gardner, Jessica C Conroy, Michael H Shaham, Clay V Styer, Geoffrey SchoenbaumAbstract:Summary How do we choose between goods that have different subjective values, like apples and oranges? Neuroeconomics proposes that this is done by reducing complex goods to a single unitary value to allow comparison. This value is computed "on the fly" from the underlying model of the goods space, allowing decisions to meet current needs. This is termed "model-based" behavior to distinguish it from pre-determined, habitual, or "model-free" behavior. The Lateral Orbitofrontal Cortex (OFC) supports model-based behavior in rats and primates, but whether the OFC is necessary for economic choice is less clear. Here we tested this question by optogenetically inactivating the Lateral OFC in rats in a classic model-based task and during economic choice. Contrary to predictions, inactivation disrupted model-based behavior without affecting economic choice.
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ensembles in medial and Lateral Orbitofrontal Cortex construct cognitive maps emphasizing different features of the behavioral landscape
Behavioral Neuroscience, 2017Co-Authors: Nina Lopatina, Michael A Mcdannald, Clay V Styer, Brian F Sadacca, Jacob F Peterson, Joseph F Cheer, Geoffrey SchoenbaumAbstract:The Orbitofrontal Cortex (OFC) has long been implicated in the ability to use the current value of expected outcomes to guide behavior. More recently, this specific role has been conceptualized as a special case of a more general function that OFC plays in constructing a "cognitive map" of the behavioral task space by labeling the current task state and learning relationships among task states. Here, we have used single unit recording data from 2 prior studies to examine whether and how information relating different states within and across trials is represented in medial versus Lateral OFC in rats. Using a hierarchical clustering analysis, we examined how neurons from each area represented information about differently valued trial types, defined by the cue-outcome pairings, versus how those same neurons represented information about similar epochs between these different trial types, such as the stimulus sample, delay, and reward consumption epochs. This analysis revealed that ensembles in the Lateral OFC (lOFC) group states according to trial epoch, whereas those in the medial OFC (mOFC) organize the same states by trial type. These results suggest that the lOFC and mOFC construct cognitive maps that emphasize different features of the behavioral landscape, with lOFC tracking events based on local similarities, irrespective of their values and mOFC tracking more distal or higher order relationships relevant to value. (PsycINFO Database Record
Mary L Phillips - One of the best experts on this subject based on the ideXlab platform.
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decreased activation of Lateral Orbitofrontal Cortex during risky choices under uncertainty is associated with disadvantageous decision making and suicidal behavior
NeuroImage, 2010Co-Authors: Fabrice Jollant, Natalia Lawrence, Owen Odaly, Mary L Phillips, Emilie Olie, Alain Malafosse, Philippe CourtetAbstract:Decision-making impairment has been linked to Orbitofrontal Cortex lesions and to different disorders including substance abuse, aggression and suicidal behavior. Understanding the neurocognitive mechanisms of these impairments could facilitate the development of effective treatments. In the current study, we aimed to explore the neural and cognitive basis of poor decision-making ability associated with the vulnerability to suicidal behavior, a public health issue in most western countries. Twenty-five not currently depressed male patients, 13 of whom had a history of suicidal acts (suicide attempters) and 12 of whom had none (affective controls), performed an adapted version of the Iowa Gambling Task during functional Magnetic Resonance Imaging. Task-related functional Regions-of-Interest were independently defined in 15 male healthy controls performing the same task (Lawrence et al., 2009). In comparison to affective controls, suicide attempters showed 1) poorer performance on the gambling task 2) decreased activation during risky relative to safe choices in left Lateral Orbitofrontal and occipital cortices 3) no difference for the contrast between wins and losses. Altered processing of risk under conditions of uncertainty, associated with left Lateral Orbitofrontal Cortex dysfunction, could explain the decision-making deficits observed in suicide attempters. These impaired cognitive and neural processes may represent future predictive markers and therapeutic targets in a field where identification of those at risk is poor and specific treatments are lacking. These results also add to our growing understanding of the role of the Orbitofrontal Cortex in decision-making and psychopathology.
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distinct roles of prefrontal cortical subregions in the iowa gambling task
Cerebral Cortex, 2009Co-Authors: Fabrice Jollant, Natalia Lawrence, Owen Odaly, Fernando Zelaya, Mary L PhillipsAbstract:The Iowa Gambling Task (IGT) assesses decision-making under initially ambiguous conditions. Neuropsychological and neuroimaging data suggest, albeit inconsistently, the involvement of numerous prefrontal cortical regions in task performance. To clarify the contributions of different prefrontal regions, we developed and validated a version of the IGT specifically modified for event-related functional magnetic resonance imaging. General decision-making in healthy males elicited activation in the ventromedial prefrontal Cortex. Choices from disadvantageous versus advantageous card decks produced activation in the medial frontal gyrus, Lateral Orbitofrontal Cortex (OFC), and insula. Moreover, activation in these regions, along with the pre-supplementary motor area (pre-SMA) and secondary somatosensory Cortex, was positively associated with task performance. Lateral OFC and pre-SMA activation also showed a significant modulation over time, suggesting a role in learning. Striato-thalamic regions responded to wins more than losses. These results both replicate and add to previous findings and help to reconcile inconsistencies in neuropsychological data. They reveal that deciding advantageously under initially ambiguous conditions may require both continuous and dynamic processes involving both the ventral and dorsal prefrontal Cortex.
Timothy E J Behrens - One of the best experts on this subject based on the ideXlab platform.
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two anatomically and computationally distinct learning signals predict changes to stimulus outcome associations in hippocampus
Neuron, 2016Co-Authors: Timothy E J Behrens, Erie D Boorman, Vani G Rajendran, Jill X OreillyAbstract:Complex cognitive processes require sophisticated local processing but also interactions between distant brain regions. It is therefore critical to be able to study distant interactions between local computations and the neural representations they act on. Here we report two anatomically and computationally distinct learning signals in Lateral Orbitofrontal Cortex (lOFC) and the dopaminergic ventral midbrain (VM) that predict trial-by-trial changes to a basic internal model in hippocampus. To measure local computations during learning and their interaction with neural representations, we coupled computational fMRI with trial-by-trial fMRI suppression. We find that suppression in a medial temporal lobe network changes trial-by-trial in proportion to stimulus-outcome associations. During interleaved choice trials, we identify learning signals that relate to outcome type in lOFC and to reward value in VM. These intervening choice feedback signals predicted the subsequent change to hippocampal suppression, suggesting a convergence of signals that update the flexible representation of stimulus-outcome associations.
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frontal Cortex and reward guided learning and decision making
Neuron, 2011Co-Authors: Maryann P Noonan, Matthew F S Rushworth, Mark E Walton, Erie D Boorman, Timothy E J BehrensAbstract:Reward-guided decision-making and learning depends on distributed neural circuits with many components. Here we focus on recent evidence that suggests four frontal lobe regions make distinct contributions to reward-guided learning and decision-making: the Lateral Orbitofrontal Cortex, the ventromedial prefrontal Cortex and adjacent medial Orbitofrontal Cortex, anterior cingulate Cortex, and the anterior Lateral prefrontal Cortex. We attempt to identify common themes in experiments with human participants and with animal models, which suggest roles that the areas play in learning about reward associations, selecting reward goals, choosing actions to obtain reward, and monitoring the potential value of switching to alternative courses of action.
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separate value comparison and learning mechanisms in macaque medial and Lateral Orbitofrontal Cortex
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Maryann P Noonan, Mark E Walton, Timothy E J Behrens, Jerome Sallet, Mark J Buckley, Matthew F S RushworthAbstract:Uncertainty about the function of Orbitofrontal Cortex (OFC) in guiding decision-making may be a result of its medial (mOFC) and Lateral (lOFC) divisions having distinct functions. Here we test the hypothesis that the mOFC is more concerned with reward-guided decision making, in contrast with the lOFC's role in reward-guided learning. Macaques performed three-armed bandit tasks and the effects of selective mOFC lesions were contrasted against lOFC lesions. First, we present analyses that make it possible to measure reward-credit assignment—a crucial component of reward-value learning—independently of the decisions animals make. The mOFC lesions do not lead to impairments in reward-credit assignment that are seen after lOFC lesions. Second, we examined how the reward values of choice options were compared. We present three analyses, one of which examines reward-guided decision making independently of reward-value learning. Lesions of the mOFC, but not the lOFC, disrupted reward-guided decision making. Impairments after mOFC lesions were a function of the multiple option contexts in which decisions were made. Contrary to axiomatic assumptions of decision theory, the mOFC-lesioned animals’ value comparisons were no longer independent of irrelevant alternatives.
