Activity In Nucleus Accumbens Research Articles

Striatal dysfunction during failed motor inhibition in children at risk for bipolar disorder

A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD. 19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative with BD, and 21 healthy comparison children completed the stop signal task in a 3 T scanner. Children at familial risk for BD exhibited increased putamen activation during unsuccessful inhibition that distinguished them from both healthy and BD children. Youths with BD exhibited reduced activation of the right nucleus accumbens during unsuccessful inhibition as compared to the other participant groups. Striatal activation patterns differ between youths at risk for BD and healthy comparison children during a motor inhibition task.

Cocaine abstinence alters nucleus accumbens firing dynamics during goal‐directed behaviors for cocaine and sucrose

Distinct subsets of nucleus accumbens (NAc) neurons differentially encode goal-directed behaviors for natural vs. drug rewards [R. M. Carelli et al. (2000)The Journal of Neuroscience, 20, 4255-4266], and the encoding of cocaine-seeking is altered following cocaine abstinence [J. A. Hollander & R. M. Carelli (2007) The Journal of Neuroscience, 27, 3535-3539]. Here, electrophysiological recording procedures were used to determine if the selective encoding of natural vs. cocaine reward by NAc neurons is: (i) maintained when the natural reinforcer is a highly palatable sweet tastant and (ii) altered by cocaine abstinence. Rats (n = 14) were trained on a multiple schedule of sucrose reinforcement and cocaine self-administration (2-3 weeks) and NAc activity was recorded during the task before and after 30 days of cocaine abstinence. Of 130 cells recorded before abstinence, 82 (63%) displayed patterned discharges (increases or decreases in firing rate, termed phasic activity) relative to operant responding for sucrose or cocaine. As in previous reports, the majority of those cells displayed nonoverlapping patterns of activity during responding for sucrose vs. cocaine. Specifically, only 17 (21%) showed similar patterns of activity (i.e. overlapping activity) across the two reinforcer conditions. After abstinence, this pattern was largely maintained, 23 of 70 phasic cells (33%) were overlapping. However, cocaine abstinence altered the overall percentage of selectively active neurons across reinforcer conditions. Specifically, significantly more neurons became selectively activated during cocaine-directed behaviors than during sucrose-directed behaviors. The results indicate that, although the selective encoding of cocaine and natural rewards is maintained even with a highly palatable substance, 30 days of cocaine abstinence dynamically alters the overall population encoding of natural and drug rewards by NAc neurons.

Variations in Maternal Behavior—Oxytocin and Reward Pathways—Peripheral Measures Matter?!

Variations in Maternal Behavior—Oxytocin and Reward Pathways—Peripheral Measures Matter?!

Mathematics Anxiety: Separating the Math from the Anxiety

Anxiety about math is tied to low math grades and standardized test scores, yet not all math-anxious individuals perform equally poorly in math. We used functional magnetic resonance imaging to separate neural activity during the anticipation of doing math from activity during math performance itself. For higher (but not lower) math-anxious individuals, increased activity in frontoparietal regions when simply anticipating doing math mitigated math-specific performance deficits. This network included bilateral inferior frontal junction, a region involved in cognitive control and reappraisal of negative emotional responses. Furthermore, the relation between frontoparietal anticipatory activity and highly math-anxious individuals' math deficits was fully mediated (or accounted for) by activity in caudate, nucleus accumbens, and hippocampus during math performance. These subcortical regions are important for coordinating task demands and motivational factors during skill execution. Individual differences in how math-anxious individuals recruit cognitive control resources prior to doing math and motivational resources during math performance predict the extent of their math deficits. This work suggests that educational interventions emphasizing control of negative emotional responses to math stimuli (rather than merely additional math training) will be most effective in revealing a population of mathematically competent individuals, who might otherwise go undiscovered.

Dietary Restraint Violations Influence Reward Responses in Nucleus Accumbens and Amygdala

Numerous studies have demonstrated that consuming high-calorie food leads to subsequent overeating by chronic dieters. The present study investigates the neural correlates of such self-regulatory failures using fMRI. Chronic dieters (n = 50) and non-dieters (n = 50) consumed either a 15-oz glass of cold water or a 15-oz milkshake and were subsequently imaged while viewing pictures of animals, environmental scenes, people, and appetizing food items. Results revealed a functional dissociation in nucleus accumbens and amygdala activity that paralleled well-established behavioral patterns of eating observed in dieters and non-dieters. Whereas non-dieters showed the greatest nucleus accumbens activity in response to food items after water consumption, dieters showed the greatest activity after consuming the milkshake. Activity in the left amygdala demonstrated the reverse interaction. Considered together with previously reported behavioral findings, the present results offer a suggested neural substrate for diet failure.

Nucleus accumbens shell, but not core, tracks motivational value of salt

To appropriately respond to an affective stimulus, we must be able to track its value across changes in both the external and internal environment. The nucleus accumbens (NAc) is a critical component of reward circuitry, but recent work suggests that the NAc encodes aversion as well as reward. It remains unknown whether differential NAc activity reflects flexible changes in stimulus value when it is altered due to a change in physiological state. We measured the activity of individual NAc neurons when rats were given intraoral infusions of a hypertonic salt solution (0.45 M NaCl) across multiple sessions in which motivational state was manipulated. This normally nonpreferred taste was made rewarding via sodium depletion, which resulted in a strong motivation to seek out and consume salt. Recordings were made in three conditions: while sodium replete (REP), during acute sodium depletion (DEP), and following replenishment of salt to normal sodium balance (POST). We found that NAc neurons in the shell and core subregions responded differently across the three conditions. In the shell, we observed overall increases in NAc activity when the salt solution was nonpreferred (REP) but decreases when the salt solution was preferred (DEP). In the core, overall activity was significantly altered only after sodium balance was restored (POST). The results lend further support to the selective encoding of affective stimuli by the NAc and suggest that NAc shell is particularly involved in flexibly encoding stimulus value based on motivational state.

Effect of catecholamines on locomotor activity and cyclic AMP in nucleus accumbens in rats.

Effect of catecholamines on locomotor activity and cyclic AMP in nucleus accumbens in rats.

Nucleus accumbens facilitates nociception

We have previously demonstrated an opioid link in nucleus accumbens (NAc) that mediates antinociception produced by a novel ascending pain modulation pathway. For example, noxious stimulation induces heterosegmental antinociception that is mediated by both mu- and delta-opioid receptors in NAc. However, spinal intrathecal administration of the mu-receptor agonist [ d-Ala 2, N-Me-Phe 4,Gly 5-ol]-enkephalin (DAMGO) also induces heterosegmental antinociception. The aim of the present study in the rat was to identify the intra-NAc opioid receptors that mediate the antinociceptive effects of spinally administered DAMGO and also to determine the effect of NAc efferent activity on nociception. Intra-NAc administration of either the mu-opioid receptor antagonist Cys 2,Tyr 3, Orn 5,Pen 7amide (CTOP) or the delta-opioid receptor antagonist naltrindole blocked the antinociceptive effect of spinally administered DAMGO on the jaw-opening reflex (JOR). Injection of quaternary lidocaine (QX-314) attenuated the JOR, suggesting that the output of NAc is pronociceptive. In support of this, intra-NAc injection of the excitatory amino acid agonist kainate enhanced the JOR. Thus, it is possible to modulate activity in NAc to bidirectionally attenuate or enhance nociception, suggesting a potential role for NAc in setting nociceptive sensitivity.

The Affective Impact of Financial Skewness on Neural Activity and Choice

Few finance theories consider the influence of “skewness” (or large and asymmetric but unlikely outcomes) on financial choice. We investigated the impact of skewed gambles on subjects' neural activity, self-reported affective responses, and subsequent preferences using functional magnetic resonance imaging (FMRI). Neurally, skewed gambles elicited more anterior insula activation than symmetric gambles equated for expected value and variance, and positively skewed gambles also specifically elicited more nucleus accumbens (NAcc) activation than negatively skewed gambles. Affectively, positively skewed gambles elicited more positive arousal and negatively skewed gambles elicited more negative arousal than symmetric gambles equated for expected value and variance. Subjects also preferred positively skewed gambles more, but negatively skewed gambles less than symmetric gambles of equal expected value. Individual differences in both NAcc activity and positive arousal predicted preferences for positively skewed gambles. These findings support an anticipatory affect account in which statistical properties of gambles—including skewness—can influence neural activity, affective responses, and ultimately, choice.

Dysfunctional Reward Circuitry in Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is primarily conceived as an anxiety disorder but has features resembling addictive behavior. Patients with OCD may develop dependency upon compulsive behaviors because of the rewarding effects following reduction of obsession-induced anxiety. Reward processing is critically dependent on ventral striatal-orbitofrontal circuitry and brain imaging studies in OCD have consistently shown abnormal activation within this circuitry. This is the first functional imaging study to investigate explicitly reward circuitry in OCD. Brain activity during reward anticipation and receipt was compared between 18 OCD patients and 19 healthy control subjects, using a monetary incentive delay task and functional magnetic resonance imaging. Reward processing was compared between OCD patients with predominantly contamination fear and patients with predominantly high-risk assessment. Obsessive-compulsive disorder patients showed attenuated reward anticipation activity in the nucleus accumbens compared with healthy control subjects. Reduced activity of the nucleus accumbens was more pronounced in OCD patients with contamination fear than in patients with high-risk assessment. Brain activity during reward receipt was similar between patients and control subjects. A hint toward more dysfunctional reward processing was found in treatment-resistant OCD patients who subsequently were successfully treated with deep brain stimulation of the nucleus accumbens. Obsessive-compulsive disorder patients may be less able to make beneficial choices because of altered nucleus accumbens activation when anticipating rewards. This finding supports the conceptualization of OCD as a disorder of reward processing and behavioral addiction.

Differential modulation of oscillatory activity in the human nucleus accumbens by face perception, target detection and novelty signaling

Event Abstract Back to Event Differential modulation of oscillatory activity in the human nucleus accumbens by face perception, target detection and novelty signaling Till R. Schneider1*, Christian K. Moll1, Alessandro Gulberti1, Kathrin Müsch11, Bartosz Zurowski2, Dirk Rasche2, Andreas Kordon2, Jan Gliemroth2, Volker M. Tronnier2 and Andreas K. Engel1 1 University Medical Center Hamburg-Eppendorf, Germany 2 University Hospital Schleswig-Holstein, Campus Lübeck, Germany The nucleus accumbens is part of the ventral striatum and numerous studies have reported increased activity in response to rewarding and aversive stimuli. In addition, the nucleus accumbens is thought to operate as a filter for task-relevant information and thus may serve target detection. We tested the involvement of the nucleus accumbens in visual face processing (Experiment 1) and in auditory target detection using a novelty-oddball task (Experiment 2). To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the ventral striatum of a patient suffering from severe obsessive compulsive disorder. In Experiment 1 faces and scrambled versions of the same faces were presented in a visual detection task. During face perception, oscillatory activity in the gamma frequency range (30-90 Hz) was selectively enhanced in the nucleus accumbens. In the novelty-oddball task (Experiment 2) frequent tones (p = 0.8) were interspersed with task-irrelevant unique ‘novel’ sounds (p = 0.1) and task-relevant target tones (p = 0.1). Oscillatory activity in the alpha (8-12 Hz) and the beta range (15-35 Hz) was enhanced in response to target compared to frequent stimuli. ‘Novel’ sounds elicited stronger activity in the alpha-range when compared to frequent stimuli, whereas target stimuli elicited enhanced beta-range activity compared to ‘novel’ sounds. Taken together, our data suggest that the distinct modulation of ventral striatal oscillatory activity plays a critical role in coding different aspects of saliency. Specifically, while beta band activity may signal top-down target detection, an increase of alpha band activity may reflect attentional gating (the bottom-up component of saliency processing) in the nucleus accumbens. Keywords: Intra-cranial Electrophysiology, Oscillatory activity Conference: XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011. Presentation Type: Poster Presentation Topic: Abstracts Citation: Schneider TR, Moll CK, Gulberti A, Müsch1 K, Zurowski B, Rasche D, Kordon A, Gliemroth J, Tronnier VM and Engel AK (2011). Differential modulation of oscillatory activity in the human nucleus accumbens by face perception, target detection and novelty signaling. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00062 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 15 Nov 2011; Published Online: 25 Nov 2011. * Correspondence: Dr. Till R Schneider, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, t.schneider@uke.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Till R Schneider Christian K Moll Alessandro Gulberti Kathrin Müsch1 Bartosz Zurowski Dirk Rasche Andreas Kordon Jan Gliemroth Volker M Tronnier Andreas K Engel Google Till R Schneider Christian K Moll Alessandro Gulberti Kathrin Müsch1 Bartosz Zurowski Dirk Rasche Andreas Kordon Jan Gliemroth Volker M Tronnier Andreas K Engel Google Scholar Till R Schneider Christian K Moll Alessandro Gulberti Kathrin Müsch1 Bartosz Zurowski Dirk Rasche Andreas Kordon Jan Gliemroth Volker M Tronnier Andreas K Engel PubMed Till R Schneider Christian K Moll Alessandro Gulberti Kathrin Müsch1 Bartosz Zurowski Dirk Rasche Andreas Kordon Jan Gliemroth Volker M Tronnier Andreas K Engel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Nucleus accumbens neurons encode predicted and ongoing reward costs in rats

Efficient decision-making requires that animals consider both the benefits and the costs of potential actions, such as the amount of effort or temporal delay involved in reward seeking. The nucleus accumbens (NAc) has been implicated in the ability to choose between options with different costs and overcome high costs when necessary, but it is not clear how NAc processing contributes to this role. Here, neuronal activity in the rat NAc was monitored using multi-neuron electrophysiology during two cost-based decision tasks in which either reward effort or reward delay was manipulated. In each task, distinct visual cues predicted high-value (low effort/immediate) and low-value (high effort/delayed) rewards. After training, animals exhibited a behavioral preference for high-value rewards, yet overcame high costs when necessary to obtain rewards. Electrophysiological analysis indicated that a subgroup of NAc neurons exhibited phasic increases in firing rate during cue presentations. In the effort-based decision task (but not the delay-based task), this population reflected the cost-discounted value of the future response. In contrast, other subgroups of cells were activated during response initiation or reward delivery, but activity did not differ on the basis of reward cost. Finally, another population of cells exhibited sustained changes in firing rate while animals completed high-effort requirements or waited for delayed rewards. These findings are consistent with previous reports that implicate NAc function in reward prediction and behavioral allocation during reward-seeking behavior, and suggest a mechanism by which NAc activity contributes to both cost-based decisions and actual cost expenditure.

Individuals Family History Positive for Alcoholism Show Functional Magnetic Resonance Imaging Differences in Reward Sensitivity That Are Related to Impulsivity Factors

Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. We investigated proposed neural correlates of substance disorder risk by examining reward system activity during a monetary incentive delay task with separate reward prospect, reward anticipation, and reward outcome phases in 30 individuals with and 19 without family histories of alcoholism. All subjects were healthy, lacked DSM-IV past or current alcohol or substance abuse histories, and were free of illegal substances as verified by a urine toxicology screening at the time of scanning. Additionally, we explored specific correlations between task-related nucleus accumbens (NAcc) activation and distinct factor analysis-derived domains of behavioral impulsivity. During reward anticipation, functional magnetic resonance imaging data confirmed blunted NAcc activation in family history positive subjects. In addition, we found atypical activation in additional reward-associated brain regions during additional task phases. We further found a significant negative correlation between NAcc activation during reward anticipation and an impulsivity construct. Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.

Dopamine transporter inhibition is necessary for cocaine‐induced increases in dendritic spine density in the nucleus accumbens

Repeated exposure to cocaine produces changes in the nervous system that facilitate drug-seeking behaviors. These drug-seeking behaviors have been studied with animal models, such as cocaine-induced locomotor sensitization. Cocaine is hypothesized to induce locomotor sensitization by neural changes, including an increase in the density of spines on the dendrites of neurons in the nucleus accumbens (NAC). However, how cocaine increases dendritic spine density in the NAC has been difficult to discern because cocaine inhibits the function of multiple targets, including the transporters for dopamine, serotonin, and norepinephrine. Previously, our lab created a tool that is useful for determining how inhibiting the dopamine transporter (DAT) contributes to the effects of cocaine by generating mice that express a cocaine-insensitive DAT (DAT-CI mice). In this study, we used DAT-CI mice to determine the contribution of DAT inhibition in cocaine-induced increases in dendritic spine density in the NAC. We repeatedly injected DAT-CI mice with either cocaine or saline, and measured both dendritic spine density in the NAC and locomotor activity. Unlike wild-type mice, DAT-CI mice did not show an increase in dendritic spine density in the NAC or in locomotor activity in response to repeated injections of cocaine. These data show that cocaine-induced increases in dendritic spine density in the NAC require DAT inhibition. Thus, DAT-inhibition may play a role in mediating the long-lasting neural changes associated with drug addiction.

Nucleus Accumbens-Derived Glial Cell Line-Derived Neurotrophic Factor Is a Retrograde Enhancer of Dopaminergic Tone in the Mesocorticolimbic System

Spontaneous firing of ventral tegmental area (VTA) dopamine (DA) neurons provides ambient levels of DA in target areas such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC). Here we report that the glial cell line-derived neurotrophic factor (GDNF), produced in one target region, the NAc, is retrogradely transported by DA neurons to the VTA where the growth factor positively regulates the spontaneous firing activity of both NAc- and PFC-projecting DA neurons in a mechanism that requires the activation of the mitogen-activated protein kinase (MAPK) pathway. We also show that the consequence of GDNF-mediated activation of the MAPK signaling cascade in the VTA is an increase in DA overflow in the NAc. Together, these results demonstrate that NAc-produced GDNF serves as a retrograde enhancer that upregulates the activity of the mesocorticolimbic DA system.

Emotional imagery: assessing pleasure and arousal in the brain's reward circuitry.

Research on emotional perception and learning indicates appetitive cues engage nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), whereas amygdala activity is modulated by the emotional intensity of appetitive and aversive cues. This study sought to determine patterns of functional activation and connectivity among these regions during narrative emotional imagery. Using event-related fMRI, we investigate activation of these structures when participants vividly imagine pleasant, neutral, and unpleasant scenes. Results indicate that pleasant imagery selectively activates NAc and mPFC, whereas amygdala activation was enhanced during both pleasant and unpleasant imagery. NAc and mPFC activity were each correlated with the rated pleasure of the imagined scenes, while amygdala activity was correlated with rated emotional arousal. Functional connectivity of NAc and mPFC was evident throughout imagery, regardless of hedonic content, while correlated activation of the amygdala with NAc and mPFC was specific to imagining pleasant scenes. These findings provide strong evidence that pleasurable text-driven imagery engages a core appetitive circuit, including NAc, mPFC, and the amygdala.

MEASURING BELIEFS AND REWARDS: A NEUROECONOMIC APPROACH.

The neurotransmitter dopamine is central to the emerging discipline of neuroeconomics; it is hypothesized to encode the difference between expected and realized rewards and thereby to mediate belief formation and choice. We develop the first formal test of this theory of dopaminergic function, based on a recent axiomatization by Caplin and Dean [2008A]. These tests are satisfied by neural activity in the nucleus accumbens, an area rich in dopamine receptors. We find evidence for separate positive and negative reward prediction error signals, suggesting that behavioral asymmetries in response to losses and gains may parallel asymmetries in nucleus accumbens activity.

Predicted Effects of a Pause in D1 and D2 Medium Spiny Neurons during Feeding: Figure 1.

A reduction in nucleus accumbens (NAc) activity is associated with an increase in feeding under several experimental conditions. In the late 1990s, Kelley et al. reported that sated rats ate “voraciously” when an AMPA antagonist or GABAA agonist was infused into the NAc shell, an effect specific

β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats

We investigated the short- and long-term effects of ceftriaxone on glutamate transporter subtype 1 (GLT-1) transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented by the GLT-1 transporter inhibitor dihydrokainate (1 μM, intra-accumbal). These results suggest that β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.

Predicting Value of Pain and Analgesia: Nucleus Accumbens Response to Noxious Stimuli Changes in the Presence of Chronic Pain

We compared brain activations in response to acute noxious thermal stimuli in controls and chronic back pain (CBP) patients. Pain perception and related cortical activation patterns were similar in the two groups. However, nucleus accumbens (NAc) activity differentiated the groups at a very high accuracy, exhibiting phasic and tonic responses with distinct properties. Positive phasic NAc activations at stimulus onset and offset tracked stimulus salience and, in normal subjects, predicted reward (pain relief) magnitude at stimulus offset. In CBP, NAc activity correlated with different cortical circuitry from that of normals and phasic activity at stimulus offset was negative in polarity, suggesting that the acute pain relieves the ongoing back pain. The relieving effect was confirmed in a separate psychophysical study in CBP. Therefore, in contrast to somatosensory pathways, which reflect sensory properties of acute noxious stimuli, NAc activity in humans encodes its predicted value and anticipates its analgesic potential on chronic pain.