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Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity.

ABSTRACT: BACKGROUND:The orbitofrontal cortex seems to play a crucial role in reward-guided learning and decision making, especially for impulsive choice procedures including delayed reward discounting. The central serotonergic system is closely involved in the regulation of impulsivity, but how the serotonergic firing rate and release, best investigated by the loudness dependence of auditory evoked potentials (LDAEP), interact with orbitofrontal activity is still unknown. METHODS:Twenty healthy volunteers (11 males, 9 females, 31.3?±?10.6 years old) were studied in a 3T MRI scanner (Philips, Hamburg, Germany) during a delay discounting task, after their LDAEP was recorded using a 32 electrodes EEG machine (Brain Products, Munich, Germany). RESULTS:Significant positive correlations were only found between the LDAEP and the medial orbitofrontal part of the superior frontal gyrus (SFG/MO) [? immediate reward - delayed reward] for the right (r?=?0.519; P?=?0.019) and left side (r?=?0.478; P?=?0.033). This relationship was stronger for females compared with males. Orbitofrontal activity was also related to the Barratt Impulsivity Scale. CONCLUSIONS:This study revealed that low serotonergic activity as measured by a strong LDAEP was related to a high fMRI signal intensity of SFG/MO during immediate reward behavior which is related to impulsivity. Since this relationship was only found for the infralimbic medial and not for the middle or lateral part of the orbitofrontal cortex, an exclusive projection tract of the serotonergic system to this cortical region can be assumed to regulate impulsive reward-orientated decision making. Hum Brain Mapp 38:1507-1517, 2017. © 2016 Wiley Periodicals, Inc.

SUBMITTER: Mavrogiorgou P

PROVIDER: S-EPMC6866894 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity.

Mavrogiorgou Paraskevi P Enzi Björn B Klimm Ann-Kristin AK Köhler Elke E Roser Patrik P Norra Christine C Juckel Georg G

Human brain mapping 20161111 3

<h4>Background</h4>The orbitofrontal cortex seems to play a crucial role in reward-guided learning and decision making, especially for impulsive choice procedures including delayed reward discounting. The central serotonergic system is closely involved in the regulation of impulsivity, but how the serotonergic firing rate and release, best investigated by the loudness dependence of auditory evoked potentials (LDAEP), interact with orbitofrontal activity is still unknown.<h4>Methods</h4>Twenty he ...[more]

PMID: 27862593

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Project description:RationaleImpulsive behavior is a deleterious component of a number of mental health disorders but has few targeted pharmacotherapies. One contributing factor to the difficulty in understanding the neural substrates of disordered impulsivity is the diverse presentations of impulsive behavior. Defining the behavioral and cognitive processes which contribute to different subtypes of impulsivity is important for understanding the neural underpinnings of dysregulated impulsive behavior.MethodsUsing a mouse model for disordered impulsivity, our goal was to identify behavioral and cognitive processes that are associated with increased impulsivity. Specifically, we were interested in the facets of impulsivity modulated by serotonin signaling. We used mice lacking the serotonin 1B receptor (5-HT1BR) and measured different types of impulsivity as well as goal-directed responding, extinction, habitual-like behavior, cue reactivity, and reward reactivity.ResultsMice lacking expression of 5-HT1BR had increased levels of impulsive action, goal-directed responding, and motivation, with no differences seen in rate of extinction, development of habitual behavior, delay discounting, or effort-based discounting. Interestingly, mice lacking 5-HT1BR expression also showed an overall increase in the choice of higher value rewards, increased hedonic responses to sweet rewards, and responded more for cues that predict reward. We developed a novel paradigm to demonstrate that increasing anticipated reward value could directly increase impulsive action. Furthermore, we found that 5-HT1BR KO-induced impulsivity could be ameliorated by decreasing the reward value relative to controls, suggesting that the increased 5-HT1BR-associated impulsive action may be a result of increased reward valuation.ConclusionsTaken together, these data show that the effects of serotonin on impulsive action are mediated through the modulation of hedonic value, which may alter the reward representations that motivate action. Overall, this data supports a role for reward value as an important substrate in impulsive action which may drive clinically relevant increases in impulsivity.

Project description:Aims: Chronic cannabis users show impairments on laboratory measures of decision making which reflect risk factors for initiation and continued use of cannabis. However, the differential sensitivity of these tasks to cannabis use has not been established. Moreover, studies to date have often lacked assessment of psychiatric histories and use of other illicit substances, both of which may influence decision making outcomes. The current study aimed to address these limitations by (1) including multiple types of decision making tasks, (2) implementing the Probabilistic Reversal Learning Task, a measure of decision making under uncertainty, for the first time in cannabis users, (3) including young adult cannabis users with no other psychiatric disorders, and (4) conducting urinalysis to exclude users of other illicit drugs. Methods: Thirty-three current cannabis users without comorbid psychiatric disorders and 35 cannabis non-users completed behavioral measures of decision-making (Iowa Gambling Task), reward discounting (Delay Discounting Task), choice-outcome learning (the Probabilistic Reversal Learning Task) and a questionnaire assessment of impulsivity (Barratt Impulsiveness Scale). Results: Relative to non-users, cannabis users demonstrated greater preference for immediate vs. delayed rewards on the Delay Discounting Task, made fewer advantageous decisions on the Iowa Gambling Task, and endorsed greater impulsivity on the Barratt Impulsiveness Scale scales. Cannabis users and non-users showed comparable performance on the Probabilistic Reversal Learning Task. Frequency of past-month cannabis use and total years of use did not predict decision making or impulsivity. Conclusions: Young adult cannabis users demonstrated higher discounting rates and impairments in learning cost-benefit contingencies, while reversal learning was unaffected. Self-reported impulsivity was elevated as well. None of these measures correlated with current or lifetime estimates of cannabis use, arguing against a dose-relationship. Interventions that target improvement in affected components of decision making may be helpful in reducing cannabis use and relapse.

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Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity.

Publications

Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity.

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