Cocaine-induced Impulsive Choices Are Accompanied by Impaired Delay-dependent Anticipatory Activity in Basolateral Amygdala

Addicts and drug-experienced animals have decision-making deficits in delayed reinforcement choice task, in which they prefer small immediate rewards over large delayed rewards. Here, we show evidence that this deficit is accompanied by changed coding of delay length in the basolateral amygdala (BLA). A subset of neurons in BLA demonstrated delay-dependent anticipatory activity (either increase or decrease as a function of delay to reward) in naive rats. After 30 days of withdrawal from chronic cocaine treatment (30 mg/kg/day for 10 days ip), the proportion of delay-dependent anticipatory neurons reduced, whereas delay-dependent activity in response to elapsed delay after reward delivery increased, both in the proportion of delay-dependent neurons and in the extent of delay dependence. Cocaine exposure increased, instead of decreased, BLA neuronal expectation for different reward magnitudes. These results indicate that BLA is critical for representing and maintaining the information of delayed reward before its delivery, and cocaine exposure may affect decision-making by impairing perception of delay instead of the ability to assess the differences in reward size.

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Prior cocaine exposure increases firing to immediate reward while attenuating cue and context signals related to reward value in anterior insula

10.1101/2020.10.01.322776 ◽

2020 ◽

Author(s):

Heather J. Pribut ◽

Daniela Vázquez ◽

Adam T. Brockett ◽

Alice D. Wei ◽

Stephen S. Tennyson ◽

...

Keyword(s):

Decision Making ◽

Behavioral Control ◽

Anterior Insula ◽

Behavioral Changes ◽

Cocaine Exposure ◽

Self Administration ◽

Neural Signals ◽

Drug Induced ◽

Chronic Cocaine ◽

Experimental Group

ABSTRACTThe insula contributes to behavioral control and is disrupted by substance abuse, yet we know little about the neural signals underlying these functions or how they are disrupted after chronic drug self-administration. Here, rats self-administered either cocaine (experimental group) or sucrose (control) for twelve consecutive days. After a one-month withdrawal period, we recorded from anterior insula while rats performed a previously learned reward-guided decision-making task. Cocaine-exposed rats were more sensitive to value manipulations and were faster to respond. These behavioral changes were accompanied by elevated counts of neurons in the insula that increased firing to reward. These neurons also fired more strongly at the start of long delay trials-when a more immediate reward would be expected, and fired less strongly in anticipation of the actual delivery of delayed rewards. Although reward-related firing to immediate reward was enhanced after cocaine self-administration, reward-predicting cue and context signals were attenuated.Significance StatementThe insula plays a clear role in drug-addiction and drug-induced impairments of decision-making, yet there is little understanding of its underlying neural signals. We found that chronic cocaine self-administration reduces cue and context-encoding in insula, while enhancing signals related to immediate reward. These changes in neural activity likely contribute to impaired decision-making and impulsivity observed after drug use.

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Noradrenergic correlates of chronic cocaine craving: neuromelanin and functional brain imaging

Neuropsychopharmacology ◽

10.1038/s41386-020-00937-9 ◽

2021 ◽

Author(s):

Wuyi Wang ◽

Simon Zhornitsky ◽

Sheng Zhang ◽

Chiang-shan R. Li

Keyword(s):

Functional Brain Imaging ◽

Cocaine Exposure ◽

Imaging Data ◽

Significant Group ◽

Motivated Behavior ◽

Chronic Cocaine ◽

Cocaine Craving ◽

Lc Circuit ◽

Psychophysiological Interaction ◽

Subcortical Regions

AbstractPreclinical studies have implicated noradrenergic (NA) dysfunction in cocaine addiction. In particular, the NA system plays a central role in motivated behavior and may partake in the regulation of craving and drug use. Yet, human studies of the NA system are scarce, likely hampered by the difficulty in precisely localizing the locus coeruleus (LC). Here, we used neuromelanin imaging to localize the LC and quantified LC neuromelanin signal (NMS) intensity in 44 current cocaine users (CU; 37 men) and 59 nondrug users (NU; 44 men). We also employed fMRI to investigate cue-induced regional responses and LC functional connectivities, as quantified by generalized psychophysiological interaction (gPPI), in CU. Imaging data were processed by published routines and the findings were evaluated with a corrected threshold. We examined how these neural measures were associated with chronic cocaine craving, as assessed by the Cocaine Craving Questionnaire (CCQ). Compared to NU, CU demonstrated higher LC NMS for all probabilistic thresholds defined of 50–90% of the peak. In contrast, NMS of the ventral tegmental area/substantia nigra (VTA/SN) did not show significant group differences. Drug as compared to neutral cues elicited higher activations of many cortical and subcortical regions, none of which were significantly correlated with CCQ score. Drug vs. neutral cues also elicited “deactivation” of bilateral parahippocampal gyri (PHG) and PHG gPPI with a wide array of cortical and subcortical regions, including the ventral striatum and, with small volume correction, the LC. Less deactivation of the PHG (r = 0.40, p = 0.008) and higher PHG-LC gPPI (r = 0.44, p = 0.003) were positively correlated with the CCQ score. In contrast, PHG-VTA/SN connectivity did not correlate with the CCQ score. Together, chronic cocaine exposure may induce higher NMS intensity, suggesting neurotoxic effects on the LC. The correlation of cue-elicited PHG LC connectivity with CCQ score suggests a noradrenergic correlate of chronic cocaine craving. Potentially compensating for memory functions as in neurodegenerative conditions, cue-elicited PHG LC circuit connectivity plays an ill-adaptive role in supporting cocaine craving.

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Robust Stability Analysis of Delay-Dependence for a Class of Switched Uncertain Systems with Time Delay

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.415.139 ◽

2013 ◽

Vol 415 ◽

pp. 139-142

Author(s):

Chi Jo Wang ◽

Juing Shian Chiou

Keyword(s):

Time Delay ◽

Stability Margin ◽

Uncertain System ◽

Switching Law ◽

Delay Dependence ◽

Robust Stability Analysis ◽

Exponentially Stable ◽

Delay Dependent ◽

Interval Systems ◽

Delay Dependent Stability

Some new criteria of delay-dependent stability for the switched time-delay uncertain system are deduced by employing time-switched method and the comparison theorem in this paper. The total activation time ratio of the switching law can be determined to guarantee the switched time-delay uncertain system is exponentially stable with stability margin . Finally, this method can be extended to switched interval systems with time-delay. Some examples are exploited to illustrate the proposed schemes..

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Delays to reward delivery enhance the preference for an initially less desirable option: role for the basolateral amygdala and retrosplenial cortex

Journal of Neuroscience ◽

10.1523/jneurosci.0438-21.2021 ◽

2021 ◽

pp. JN-RM-0438-21

Author(s):

Merridee J. Lefner ◽

Alexa P. Magnon ◽

James M. Gutierrez ◽

Matthew R. Lopez ◽

Matthew J. Wanat

Keyword(s):

Basolateral Amygdala ◽

Retrosplenial Cortex ◽

Reward Delivery

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Sensitivity to gains during risky decision-making differentiates chronic cocaine users from stimulant-naïve controls

10.1101/795443 ◽

2019 ◽

Author(s):

B. Kluwe-Schiavon ◽

A. Kexel ◽

G. Manenti ◽

D.M. Cole ◽

M.R. Baumgartner ◽

...

Keyword(s):

Decision Making ◽

Neuropsychological Test ◽

Risky Decision Making ◽

Risky Decision ◽

Cocaine Use ◽

Risk Seeking ◽

Chronic Cocaine ◽

Increased Risk ◽

Cocaine Users ◽

The Individual

AbstractBackgroundAlthough chronic cocaine use has been frequently associated with decision-making impairments that are supposed to contribute to the development and maintenance of cocaine addiction, it has remained unclear how risk-seeking behaviours observed in chronic cocaine users (CU) come about. Here we therefore test whether risky decision-making observed in CU is driven by alterations in individual sensitivity to the available information (gain, loss, and risk).MethodA sample of 96 participants (56 CU and 40 controls) performed the no-feedback (“cold”) version of the Columbia Card Task. Structured psychiatric interviews and a comprehensive neuropsychological test battery were additionally conducted. Current and recent substance use was objectively assessed by toxicological urine and hair analysis.ResultsCompared to controls, CU showed increased risk-seeking in unfavourable decision scenarios in which the risk was high and the returns were low, and a tendency for increased risk aversion in favourable decision scenarios. These differences arose from the fact that CU were less sensitive to gain, but similarly sensitive to loss and risk information in comparison to controls. Further analysis revealed that individual differences in sensitivity to loss and risk were related to cognitive performance and impulsivity.ConclusionThe reduced sensitivity to gain information in people with CU may contribute to their propensity for making risky decisions. While these alterations in the sensitivity to gain might be directly related to cocaine use per se, the individual psychopathological profile of CU might moderate their sensitivity to risk and loss impulsivity.

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Target Detection by Opponent Coding in Monkey Prefrontal Cortex

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21216 ◽

2010 ◽

Vol 22 (4) ◽

pp. 751-760 ◽

Cited By ~ 17

Author(s):

Makoto Kusunoki ◽

Natasha Sigala ◽

Hamed Nili ◽

David Gaffan ◽

John Duncan

Keyword(s):

Decision Making ◽

Target Detection ◽

Neural Model ◽

Stimulus Onset ◽

Stimulus Category ◽

Flexible Control ◽

Cell Groups ◽

Show Evidence ◽

Context Specific ◽

Monkey Prefrontal Cortex

The pFC plays a key role in flexible, context-specific decision making. One proposal [Machens, C. K., Romo, R., & Brody, C. D. Flexible control of mutual inhibition: A neural model of two-interval discrimination. Science, 307, 1121–1124, 2005] is that prefrontal cells may be dynamically organized into opponent coding circuits, with competitive groups of cells coding opposite behavioral decisions. Here, we show evidence for extensive, temporally evolving opponent organization in the monkey pFC during a cued target detection task. More than a half of all randomly selected cells discriminated stimulus category in this task. The largest set showed target-positive activity, with the strongest responses to the current target, intermediate activity for a nontarget that was a target on other trials, and lowest activity for nontargets never associated with the target category. Second most frequent was a reverse, antitarget pattern. In the ventrolateral frontal cortex, opponent organization was strongly established in phasic responses at stimulus onset; later, such activity was widely spread across dorsolateral and ventrolateral sites. Task-specific organization into opponent cell groups may be a general feature of prefrontal decision making.

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B.7 - 5-HT2A RECEPTORS IN THE ORBITOFRONTAL CORTEX AND THE BASOLATERAL AMYGDALA MODULATE IMPULSIVE DECISION-MAKING IN RATS

Behavioural Pharmacology ◽

10.1097/01.fbp.0000434779.36485.a7 ◽

2013 ◽

Vol 24 ◽

pp. e28

Author(s):

Lena Wischhof ◽

Kerstin Wernecke ◽

Ellen Irrsack ◽

Malte Feja ◽

Michael Koch

Keyword(s):

Decision Making ◽

Orbitofrontal Cortex ◽

Basolateral Amygdala

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Decision Biases and Heuristics Among Emergency Managers: Just Like the Public They Manage For?

The American Review of Public Administration ◽

10.1177/0275074018799490 ◽

2018 ◽

Vol 49 (3) ◽

pp. 292-308 ◽

Cited By ~ 7

Author(s):

Patrick S. Roberts ◽

Kris Wernstedt

Keyword(s):

Decision Making ◽

Structured Decision Making ◽

The Public ◽

Public Managers ◽

Emergency Managers ◽

Decision Biases ◽

Show Evidence ◽

Decision Making Processes ◽

Outcome Bias ◽

Attribution Bias

We present evidence that emergency managers exhibit some of the same decision biases, sensitivity to framing, and heuristics found in studies of the general public, even when making decisions in their area of expertise. Our national survey of county-level emergency managers finds that managers appear more risk averse when the outcomes of actions are framed as gains than when equivalent outcomes are framed as losses, a finding that is consistent with prospect theory. We also find evidence that the perceived actions of emergency managers in neighboring jurisdictions affect the choices a manager makes. In addition, our managers show evidence of attribution bias, outcome bias, and difficulties processing numerical information, particularly probabilities compared to frequencies. Each of these departures from perfect rationality points to potential shortfalls in public managers’ decision making. We suggest opportunities to improve decision making through reframing problems, providing training in structured decision-making processes, and employing different choice architectures to nudge behavior in a beneficial direction.

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