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Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked by loss of control and eating despite fullness. Does altered reward and metabolic state contribute to BN pathophysiology? Normally, hunger increases (and satiety decreases) reward salience to regulate eating. We investigated whether BN is associated with an abnormal response in a neural circuit involved in translating taste signals into motivated behavior, when hungry and fed. Twenty-six women remitted from BN (RBN) and 22 control women (CW) were administered water and sucrose during 2 counterbalanced fMRI visits, following a 16-hr fast or a standardized breakfast. Significant Group × Condition interactions were found in the left putamen, insula, and amygdala. Post hoc analyses revealed CW were significantly more responsive to taste stimuli when hungry versus fed in the left putamen and amygdala. In contrast, RBN response did not differ between conditions. Further, RBN had greater activation in the left amygdala compared with CW when fed. Findings suggest that RBN neural response to rewarding stimuli may not be modulated by metabolic state. Data raise the possibility that disinhibited eating in BN could result from a failure to devalue food reward when fed, resulting in an exaggerated response. (PsycINFO Database Record

Although optimizing decisions between drives to avoid pain and to obtain reward are critical for survival, understanding the neuronal circuit activity that regulates choice during approach-avoidance conflicts is limited. Here, we recorded neuronal activity in the infralimbic (IL) cortex and nucleus accumbens (NAc) during an approach-avoidance task. In this task, disruption of approach by a pain-predictive cue (PPC-avoidance) is extinguished by experience and reinstated in a model of chronic pain. In the IL-NAc circuit, the activity of distinct subpopulations of neurons predicts the extent of PPC-avoidance observed. Furthermore, chemogenetic and optogenetic manipulations establish that IL-NAc circuitry regulates PPC-avoidance behavior. Our results indicate that IL-NAc circuitry is engaged during approach-avoidance conflicts, and modifications of this circuit by experience and chronic pain determine whether approach or avoidance occurs.

Background: The female sex hormones estradiol (E) and progesterone (P) galvanize the ventral striatal reward pathway. E elevates ventral striatal dopamine and accelerates drug-cued reinstatement, while P has opposing ‘protective’ effects on drug-related behavior. We hypothesize that women may exhibit greater ventral striatal responses to smoking cues (SCs) during the late follicular phase of the menstrual cycle (MC) when E is high and unimpeded by P, and reduced responses during the late luteal phase when P is high. Methods: To test our hypothesis, 24 naturally cycling cigarette-dependent women completed functional magnetic resonance (fMRI) sessions over the course of 3 MCs at select time points to reflect the early follicular (low E and P; LEP, control condition), late follicular (high E, low P; HE) and mid-luteal (high E, high P; HEP) MC phases. During fMRI sessions (counterbalanced by phase), women were exposed to a SC versus nonSC audio-visual clip. Ovulation was verified for each MC, and hormone levels were acquired prior to sessions. Results: Contrasts within conditions showed that ventral striatal brain responses to SCs versus nonSCs were negligible during LEP and greater during HE (p=0.009) and HP (p=0.016). Contrasts across conditions showed that HE and HEP had greater responses than LEP (p=0.005), and HE had greater responses than HEP (p=0.049). Conclusions: Results support and extend our retrospective cross-sectional study of the influence of the hormonal milieu on SC reactivity. Results are clinically relevant as they may guide novel, hormonally-informed and immediately translatable treatment strategies that can potentially reduce relapse in naturally cycling women.

• we examined activation and functional connectivity (FC) in four subregions of bilateral ventral striatum (VS) in schizophrenia. • We found schizophrenia group showed higher values of fractional amplitude of low-frequency fluctuations (fALFF) than healthy control in four subregions of VS. • Using four subregions of VS as seeds, the increased FC in schizophrenia was mainly between the inferior subregions of VS and multiple brain regions including the thalamus, putamen, posterior cingulate gyrus (PCC), frontal cortex and caudate. • We found that there was a positive correlation between positive symptoms and fALFF values of the bilateral VS subregions in schizophrenia. Furthermore, the functional connectivity between the inferior subregions of VS and the brain regions aforementioned was positively correlated with the severity of negative symptoms. Schizophrenia patients frequently present with structural and functional abnormalities of the ventral striatum (VS). we examined basal activation state and functional connectivity (FC) in four subregions of the bilateral ventral striatum: left inferior ventral striatum (VSi_L), left superior ventral striatum(VSs_L), right inferior ventral striatum(VSi_R), and right superior ventral striatum(VSs_R). Resting-state functional magnetic resonance images were obtained from 62 schizophrenia patients (SCH), 57 bipolar disorder (BD) patients, and 26 healthy controls (HCs). The schizophrenia group exhibited greater fALFF in bilateral VS subregions compared to BD and HC groups as well as greater FC between the bilateral VSi and multiple brain regions, including the thalamus, putamen, posterior cingulate gyrus (PCC), frontal cortex and caudate. Moreover, the fALFF values of the bilateral ventral striatum were positively correlated with the severity of positive symptoms. We also found the functional connectivity between the bilateral inferior ventral striatum and some brain regions aforementioned were positively correlated with the severity of negative symptoms. These findings confirm a crucial contribution of ventral striatum dysfunction, especially of the bilateral VSi in schizophrenia. Functionally dissociated regions of the ventral striatum are differentially disturbed in schizophrenia. [ABSTRACT FROM AUTHOR]

The putamen is thought to generate habitual actions by processing value information relayed from the ventral striatum through the caudate nucleus. However, it is a question what value the putamen neurons process and whether the putamen receives serially processed value through the striatal structures. We found that neurons in the primate putamen, caudate, and ventral striatum selectively encoded flexibly updated values for adaptive behaviors with similar learning speeds, rather than stably sustained values for habit. In reversal value learning, rostral striatum neurons dynamically adjusted their responses to object values in alignment with changes in saccade reaction times following reversals. Notably, the value acquisition speeds within trials were similar, proposing a parallel value update in each striatal region. However, in stable value retrieval, most did not encode the values for habitual saccades. Our findings suggest that the rostral striatum including the putamen is selectively involved in the parallel processing of cognitive flexibility. [Display omitted] • Neurons in the rostral putamen of monkeys are involved in cognitive flexibility. • The rostral putamen neurons do not encode habitual stability. • Three structures in the rostral striatum update flexible value with similar speeds. • A model of parallel value processing is proposed based on similar update speeds. [ABSTRACT FROM AUTHOR]

• A longitudinal study identified specific changes of ventral striatum-related brain structural covariance and gray matter volume in first-episode patients with major depression disorder. • Patients with MDD exhibit specific cortico-ventral striatum-related reward network changes over time at the onset and one-year effective treatment after. • These findings facilitate further understanding of the pathogenesis and neuroplasticity in the onset and development of the MDD. Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD. [ABSTRACT FROM AUTHOR]

Why do people often exhaust unregulated common (shared) natural resources but manage to preserve similar private resources? To answer this question, in this study we combine a neurobiological, economic and cognitive modeling approach. Using functional magnetic resonance imaging on 50 participants, we show that a sharp decrease of common and private resources is associated with deactivation of the ventral striatum, a brain region involved in the valuation of outcomes. Across individuals, when facing a common resource, ventral striatal activity is anticorrelated with resource preservation (less harvesting), whereas with private resources the opposite pattern is observed. This indicates that neural value signals distinctly modulate behavior in response to the depletion of common vs private resources. Computational modeling suggested that overharvesting of common resources was facilitated by the modulatory effect of social comparison on value signals. These results provide an explanation of people's tendency to over-exploit unregulated common natural resources. [ABSTRACT FROM AUTHOR]

The limbic system describes a complex of brain structures central for memory, learning, as well as goal directed and emotional behavior. In addition to pathological studies, recent findings using in vivo structural and functional imaging of the brain pinpoint the vulnerability of limbic structures to neurodegeneration in Parkinson's disease (PD) throughout the disease course. Accordingly, dysfunction of the limbic system is critically related to the symptom complex which characterizes PD, including neuropsychiatric, vegetative, and motor symptoms, and their heterogeneity in patients with PD. The aim of this systematic review was to put the spotlight on neuroimaging of the limbic system in PD and to give an overview of the most important structures affected by the disease, their function, disease related alterations, and corresponding clinical manifestations. PubMed was searched in order to identify the most recent studies that investigate the limbic system in PD with the help of neuroimaging methods. First, PD related neuropathological changes and corresponding clinical symptoms of each limbic system region are reviewed, and, finally, a network integration of the limbic system within the complex of PD pathology is discussed. [ABSTRACT FROM AUTHOR]

Self-control is important for long-term success and could be a protective factor against maladaptive behaviours such as excessive gaming activity or Internet gaming disorder (IGD). However, the neurobiological basis of self-control and its relationship to IGD remain elusive. Using resting-state fMRI data from 89 participants aged from 18 to 26, we found that self-control and the number of IGD symptoms (IGD-S) were positively and negatively correlated with functional connectivity between right ventral striatum (rVS) and dorsal anterior cingulate cortex (dACC), respectively. A mediation analysis indicated that self-control influenced IGD-S partially through the rVS-dACC connectivity. In addition, step-wise regression analyses revealed that the rVS connectivity in a reward-anticipation limbic pathway contributed to IGD-S but not self-control, independent of the dACC pathway. These results suggest that the cingulate-ventral striatal functional connectivity may serve as an important neurobiological underpinning of self-control to regulate maladaptive behaviours such as these manifesting IGD through striatal circuitry balance. [ABSTRACT FROM AUTHOR]

Estrogens affect dopamine‐dependent diseases/behavior and have rapid effects on dopamine release and receptor availability in the nucleus accumbens (NAc). Low levels of nuclear estrogen receptor (ER) α and ERβ are seen in the NAc, which cannot account for the rapid effects of estrogens in this region. G‐protein coupled ER 1 (GPER1) is observed at low levels in the NAc shell, which also likely does not account for the array of estrogens' effects in this region. Prior studies demonstrated membrane‐associated ERs in the dorsal striatum; these experiments extend those findings to the NAc core and shell. Single‐ and dual‐immunolabeling electron microscopy determined whether ERα, ERβ, and GPER1 are at extranuclear sites in the NAc core and shell and whether ERα and GPER1 were localized to catecholaminergic or γ‐aminobutyric acid‐ergic (GABAergic) neurons. All three ERs are observed, almost exclusively, at extranuclear sites in the NAc, and similarly distributed in the core and shell. ERα, ERβ, and GPER1 are primarily in axons and axon terminals suggesting that estrogens affect transmission in the NAc via presynaptic mechanisms. About 10% of these receptors are found on glia. A small proportion of ERα and GPER1 are localized to catecholaminergic terminals, suggesting that binding at these ERs alters release of catecholamines, including dopamine. A larger proportion of ERα and GPER1 are localized to GABAergic dendrites and terminals, suggesting that estrogens alter GABAergic transmission to indirectly affect dopamine transmission in the NAc. Thus, the localization of ERs could account for the rapid effects of estrogen in the NAc. [ABSTRACT FROM AUTHOR]

Background: Abnormal processing of social feedback is an important contributor to social dysfunction in depression, however the exact mechanisms remain unclear. One important factor may be the extent to which social processing depends on expectations, in particular whether social feedback confirms or violates expectations. Methods: To answer this question, we studied behavioral and brain responses during the evaluative processing of social feedback in 25 individuals with subthreshold depression (SD) and 25 healthy controls (HCs). Participants completed a Social Judgment Task in which they first indicated expectation about whether a peer would like them or not, and then received peer's feedback indicating acceptance or rejection. Results: Individuals with SD who reported greater depressive symptoms gave fewer positive expectations. Compared to HCs, individuals with SD showed reduced activation in the medial prefrontal cortex when expecting positive feedback. They also exhibited increased dorsal anterior cingulate cortex after receipt of unexpected social rejection, and reduced ventral striatum activity after receipt of unexpected social acceptance. Conclusions: The observed alternations are specific to unexpected social feedback processing and highlight an important role of expectancy violation in the brain dysfunction of social feedback perception and evaluation in individuals at risk for depression. [ABSTRACT FROM AUTHOR]

Social relationships change across the lifespan as social networks narrow and motivational priorities shift to the present. Interestingly, aging is also associated with changes in executive function, including decision-making abilities, but it remains unclear how age-related changes in both domains interact to impact financial decisions involving other people. To study this problem, we recruited 50 human participants (Nyounger = 26, ages 18–34; Nolder = 24, ages 63–80) to play an economic trust game as the investor with three partners (friend, stranger, and computer) who played the role of investee. Investors underwent functional magnetic resonance imaging (fMRI) during the trust game while investees were seated outside of the scanner. Building on our previous work with younger adults showing both enhanced striatal responses and altered default-mode network (DMN) connectivity as a function of social closeness during reciprocated trust, we predicted that these relations would exhibit age-related differences. We found that striatal responses to reciprocated trust from friends relative to strangers and computers were blunted in older adults relative to younger adults, thus supporting our primary pre-registered hypothesis regarding social closeness. We also found that older adults exhibited enhanced DMN connectivity with the temporoparietal junction (TPJ) during reciprocated trust from friends compared to computers while younger adults exhibited the opposite pattern. Taken together, these results advance our understanding of age-related differences in sensitivity to social closeness in the context of trusting others.

Dopamine neurons in the ventral tegmental area (VTA) were previously found to express vesicular glutamate transporter 2 (VGLUT2) and to co-transmit glutamate in the ventral striatum (VStr). This capacity may play an important role in reinforcement learning. Although it is known that activation of the VTA-VStr dopamine system readily reinforces behavior, little is known about the role of glutamate co-transmission in such reinforcement. By combining electrode recording and optogenetics, we found that stimulation of VTA dopamine neurons in vivo evoked fast excitatory responses in many VStr neurons of adult mice. Whereas conditional knockout of the gene encoding VGLUT2 in dopamine neurons largely eliminated fast excitatory responses, it had little effect on the acquisition of conditioned responses reinforced by dopamine neuron activation. Therefore, glutamate co-transmission appears dispensable for acquisition of conditioned responding reinforced by DA neuron activation.

BackgroundExaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).MethodParticipants (SAD n=58; HC n=16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Repeated measures multi-level modeling analyses were used to examine group differences in time course activity during speech vs. control anticipation for regions of interest, including bilateral amygdala, insula, ventral striatum, and dorsal anterior cingulate cortex.ResultsThe time course of amygdala activity was more prolonged and less variable throughout speech anticipation in SAD participants compared to HCs, whereas the overall magnitude of amygdala response did not differ between groups. Magnitude and time course of activity was largely similar between groups across other regions of interest.LimitationsAnalyses were restricted to regions of interest and task order was the same across participants due to the nature of deception instructions.ConclusionsSustained amygdala time course during anticipation may uniquely reflect heightened detection of threat or deficits in emotion regulation in socially anxious individuals. Findings highlight the importance of examining temporal dynamics of amygdala responding.

BackgroundChronic methamphetamine use may lead to changes in reward-related function of the ventral striatum and caudate nucleus. Whether methamphetamine-dependent individuals show heightened reactivity to positively valenced stimuli (i.e. positive reinforcement mechanisms), or an exaggerated response to negatively valenced stimuli (i.e. driven by negative reinforcement mechanisms) remains unclear. This study investigated neural functioning of expectancy and receipt for gains and losses in adults with (METH+) and without (METH-) histories of methamphetamine dependence.MethodsParticipants (17 METH+; 23 METH-) performed a probabilistic feedback expectancy task during blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). Participants were given visual cues probabilistically associated with monetary gain, loss, or neutral outcomes. General linear models examined the BOLD response to: (1) anticipation of gains and losses, and (2) gain and loss monetary outcomes.ResultsMETH+ had less BOLD response to loss anticipation than METH- in the ventral striatum and posterior caudate. METH+ also showed more BOLD response to loss outcomes than to gain outcomes in the anterior and posterior caudate, whereas METH- did not show differential responses to the valence of outcomes.DiscussionMETH+ individuals showed attenuated neural response to anticipated gains and losses, but their response to loss outcomes was greater than to gain outcomes. A decreased response to loss anticipation, along with a greater response to loss outcomes, suggests an altered ability to evaluate future risks and benefits based upon prior experience, which may underlie suboptimal decision-making in METH+ individuals that increases the likelihood of risky behavior.

Adolescence is a time in development when significant changes occur in affective neurobiology. These changes provide a prolonged period of plasticity to prepare the individual for independence. However, they also render the system highly vulnerable to the effects of environmental stress exposures. Here, we review the human literature on the associations between stress-exposure and developmental changes in amygdala, prefrontal cortex, and ventral striatal dopaminergic systems during the adolescent period. Despite the vast differences in types of adverse exposures presented in his review, these neurobiological systems appear consistently vulnerable to stress experienced during development, providing putative mechanisms to explain why affective processes that emerge during adolescence are particularly sensitive to environmental influences.

Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2, an independent sample of 20 methamphetamine-dependent and 18 control subjects completed the Barratt Impulsiveness Scale in addition to fMRI. Study 1 showed a significant group by ventral striatal BPND interaction effect on RSFC, reflecting a negative relationship between ventral striatal BPND and RSFC between the midbrain and striatum, orbitofrontal cortex and insula in methamphetamine-dependent participants, but a positive relationship in the control group. In Study 2, an interaction of the group with RSFC on impulsivity was observed. Methamphetamine-dependent users exhibited a positive relationship of midbrain RSFC to the left ventral striatum with cognitive impulsivity, whereas a negative relationship was observed in healthy controls. The results indicate that ventral striatal D2-type receptor signaling may affect the system-level activity within the mesocorticolimbic system, providing a functional link that may help explain high impulsivity in methamphetamine-dependent individuals.

Major depressive disorder (MDD) is associated with dysfunctional corticolimbic networks, making functional connectivity studies integral for understanding the mechanisms underlying MDD pathophysiology and treatment. Resting-state functional connectivity (RSFC) studies analyze patterns of temporally coherent intrinsic brain activity in "resting-state networks" (RSNs). The default-mode network (DMN) has been of particular interest to depression research; however, a single RSN is unlikely to capture MDD pathophysiology in its entirety, and the DMN itself can be characterized by multiple RSNs. This, coupled with conflicting previous results, underscores the need for further research. Here, we measured RSFC in MDD by targeting RSNs overlapping with corticolimbic regions and further determined whether altered patterns of RSFC were restored with electroconvulsive therapy (ECT). MDD patients exhibited hyperconnectivity between ventral striatum (VS) and the ventral default-mode network (vDMN), while simultaneously demonstrating hypoconnectivity with the anterior DMN (aDMN). ECT influenced this pattern: VS-vDMN hyperconnectivity was significantly reduced while VS-aDMN hypoconnectivity only modestly improved. RSFC between the salience RSN and dorsomedial prefrontal cortex was also reduced in MDD, but was not affected by ECT. Taken together, our results support a model of ventral/dorsal imbalance in MDD and further suggest that the VS is a key structure contributing to this desynchronization.

The current study utilized resting-state functional magnetic resonance imaging (fMRI) to examine how two important non-cognitive skills, grit and growth mindset, are associated with cortico-striatal networks important for learning. Whole-brain seed-to-voxel connectivity was examined for dorsal and ventral striatal seeds. While both grit and growth mindset were associated with functional connectivity between ventral striatal and bilateral prefrontal networks thought to be important for cognitive-behavioral control. There were also clear dissociations between the neural correlates of the two constructs. Grit, the long-term perseverance towards a goal or set of goals, was associated with ventral striatal networks including connectivity to regions such as the medial prefrontal and rostral anterior cingulate cortices implicated in perseverance, delay and receipt of reward. Growth mindset, the belief that effort can improve talents, notably intelligence, was associated with both ventral and dorsal striatal connectivity with regions thought to be important for error-monitoring, such as dorsal anterior cingulate cortex. Our findings may help construct neurocognitive models of these non-cognitive skills and have critical implications for character education. Such education is a key component of social and emotional learning, ensuring that children can rise to challenges in the classroom and in life.

Parental depression is a significant risk factor for adolescents' engagement in risk taking. Yet the neural processes that mediate the link between parental depression and adolescents' functioning remain unknown. Using a longitudinal functional magnetic resonance imaging design, we investigated how parental depression is associated with changes in adolescents' neural reactivity to rewards during a risk-taking task, and how such changes in neural reactivity are associated with changes in risk-taking behavior. Greater parental depressive symptoms were associated with increases in their adolescent child's risk taking and self-reported externalizing behavior over time. At the neural level, adolescents of parents with greater depressive symptoms showed longitudinal increases in the ventral striatum and dorsolateral prefrontal cortex to rewards during risk taking. Longitudinal increases in adolescents' ventral striatum activation mediates the link between greater parental depression and increases in adolescents' risk taking and externalizing behavior. These findings provide novel evidence that parental depression may contribute to changes in adolescents' neural reactivity to rewards over time, which is associated with greater increases in their risk taking and externalizing behavior.

Loneliness is a distressing state indicating that one's basic need for social connection is not being met. In an effort to satisfy the need for social connection, loneliness may increase the processing of social cues and desire to connect with others. Yet the neural substrates that contribute to the drive for increased connection in response to loneliness are not known. The ventral striatum (VS), previously shown to increase in response to craving food and other rewarding stimuli, may contribute to "social craving" when one is lonely. That is, the VS may track one's 'hunger' for reconnection much as it tracks hunger for food. To examine this, participants reported on their feelings of loneliness before undergoing an fMRI scan where they viewed cues of potential social reconnection (images of a close other). Consistent with the hypothesis that loneliness stems from an unmet need for connection, loneliness was associated with reduced feelings of connection with the close other. Furthermore, greater reported loneliness was associated with increased VS activity to viewing a close other (vs stranger). Results extend the current literature by showing that lonely individuals show increased activity in reward-related regions to their closest loved ones, possibly reflecting an increased desire for social connection.

It is thought that frontostriatal circuits play an important role in mediating conditioned behavioral responses to environmental stimuli that were previously encountered during drug administration. However, the neural correlates of conditioned responses to drug-associated cues are not well understood at the level of large populations of simultaneously recorded neurons, or at the level of local field potential (LFP) synchrony in the frontostriatal network. Here we introduce a behavioral assay of conditioned arousal to cocaine cues involving pupillometry in awake head-restrained mice. After just 24 h of drug abstinence, brief exposures to olfactory stimuli previously paired with cocaine injections led to a transient dilation of the pupil, which was greater than the dilation effect to neutral cues. In contrast, there was no cue-selective change in locomotion, as measured by the rotation of a circular treadmill. The behavioral assay was combined with simultaneous recordings from dozens of electrophysiologically identified units in the medial prefrontal cortex (mPFC) and ventral striatum (VS). We found significant relationships between cocaine cue-evoked pupil dilation and the proportion of inhibited principal cells in the mPFC and VS. Additionally, LFP coherence analysis revealed a significant correlation between pupillary response and synchrony in the 25-45 Hz frequency band. Together, these results show that pupil dilation is sensitive to drug-associated cues during acute stages of abstinence, and that individual animal differences in this behavioral arousal response can be explained by two complementary measures of frontostriatal network activity.

Self-affirmation (reflecting on important personal values) has been shown to have a range of positive effects; however, the neural basis of self-affirmation is not known. Building on studies showing that thinking about self-preferences activates neural reward pathways, we hypothesized that self-affirmation would activate brain reward circuitry during functional MRI (fMRI) studies. In Study 1, with college students, making judgments about important personal values during self-affirmation activated neural reward regions (i.e., ventral striatum), whereas making preference judgments that were not self-relevant did not. Study 2 replicated these results in a community sample, again showing that self-affirmation activated the ventral striatum. These are among the first fMRI studies to identify neural processes during self-affirmation. The findings extend theory by showing that self-affirmation may be rewarding and may provide a first step toward identifying a neural mechanism by which self-affirmation may produce a wide range of beneficial effects.

ObjectiveGiven the association between maternal caregiving behavior and heightened neural reward activity in experimental animal studies, the present study examined whether motherhood in humans positively modulates reward-processing neural circuits, even among mothers exposed to various life stressors and depression.MethodsSubjects were 77 first-time mothers and 126 nulliparous young women from the Pittsburgh Girls Study, a longitudinal study beginning in childhood. Subjects underwent a monetary reward task during functional magnetic resonance imaging in addition to assessment of current depressive symptoms. Life stress was measured by averaging data collected between ages 8-15 years. Using a region-of-interest approach, we conducted hierarchical regression to examine the relationship of psychosocial factors (life stress and current depression) and motherhood with extracted ventral striatal (VST) response to reward anticipation. Whole-brain regression analyses were performed post-hoc to explore non-striatal regions associated with reward anticipation in mothers vs nulliparous women.ResultsAnticipation of monetary reward was associated with increased neural activity in expected regions including caudate, orbitofrontal, occipital, superior and middle frontal cortices. There was no main effect of motherhood nor motherhood-by-psychosocial factor interaction effect on VST response during reward anticipation. Depressive symptoms were associated with increased VST activity across the entire sample. In exploratory whole brain analysis, motherhood was associated with increased somatosensory cortex activity to reward (FWE cluster forming threshold p

[Display omitted] • Lateral Nucleus Accumbens D1 and D2 neuronal populations concurrently respond to the onset of freely licking and predict licking across days. • D1 and D2 licking-related responses are context-dependent. • D1 and D2 neurons are organized into ensembles with characteristic activation dynamics around sucrose intake. • D1 and D2 ensembles adapt to the behavioral context to monitor task-relevant events and sucrose concentrations. The palatability and concentration of sweet foods promote hedonic feeding beyond homeostatic need. Understanding how neurons respond to sweet taste is thus of great importance. The dorsomedial nucleus accumbens shell (dNAcMed) is considered a "sensory sentinel," promoting hedonic feeding. However, it is unknown how neurons in the lateral part (NAcLat) respond to oral sucrose stimulation. Using in vivo calcium imaging of individual D1 and D2 cells in NAcLat of mice performing behavioral licking tasks, we find that D1 and D2 neurons do not act as single homogeneous populations. Instead, their responses are organized into ensembles with context-dependent temporal dynamics around licking sucrose. At the macrostructure of licking (meals), D1 and D2 population activity recorded on the first day predict the licking behavior on subsequent days. However, at the level of the microstructure of licking (bouts), calcium activity increased concurrently in D1 and D2 neurons prior to licking bouts, whereas during licking, calcium signals decreased. Importantly, in a Brief Access Taste Task, calcium responses for D1 and D2 exhibit much more heterogeneity than during a freely licking task. Specifically, D1 and D2 neurons form distinct ensembles: some ramp up in anticipation of the first lick, some respond at the end of the taste-access period, and some categorize sucrose concentrations as low or high. Collectively, NAcLat D1 and D2 neurons are organized in ensembles that adapt to the behavioral context to monitor task-relevant events and sucrose concentrations. [ABSTRACT FROM AUTHOR]

Although living in social groups provides many benefits for group members, such groups also serve as a setting for social competition over rank and influence. Evolutionary accounts suggest that social anxiety plays a role in regulating in-group conflict, as individuals who are concerned about social threat may choose to defer to others to maintain the hierarchical status quo. Here, we examine how social anxiety levels are related to the advice-giving style an individual adopts: a competitive influence-seeking strategy or a defensive blend-in strategy. We begin by demonstrating that similarity to others drives activity in the brain's valuation system, even during a competitive advice-taking task. Then, in three behavioural experiments, we show that social anxiety levels are related to the tendency to give advice resembling the advice given by rival advisers and to refrain from status-seeking behaviour. Social anxiety was also associated with negative social comparisons with rival advisers. Our findings highlight the role of competing social goals in shaping information sharing. [ABSTRACT FROM AUTHOR]

Food odour is a potent stimulus of food intake. Odour coding in the brain occurs in synergy or competition with other sensory information and internal signals. For eliciting feeding behaviour, food odour coding has to gain signification through enrichment with additional labelling in the brain. Since the ventral striatum, at the crossroads of olfactory and reward pathways, receives a rich dopaminergic innervation, we hypothesized that dopamine plays a role in food odour information processing in the ventral striatum. Using single neurones recordings in anesthetised rats, we show that some ventral striatum neurones respond to food odour. This neuronal network displays a variety of responses (excitation, inhibition, rhythmic activity in phase with respiration). The localization of recorded neurones in a 3-dimensional brain model suggests the spatial segregation of this food-odour responsive population. Using local field potentials recordings, we found that the neural population response to food odour was characterized by an increase of power in the beta-band frequency. This response was modulated by dopamine, as evidenced by its depression following administration of the dopaminergic D1 and D2 antagonists SCH23390 and raclopride. Our results suggest that dopamine improves food odour processing in the ventral striatum. [ABSTRACT FROM AUTHOR]

Abstract Background Alcohol Use Disorder is a severe mental disorder affecting the individuals concerned, their family and friends and society as a whole. Despite its high prevalence, novel treatment options remain rather limited. Two innovative interventions used for treating severe disorders are the use of real-time functional magnetic resonance imaging neurofeedback that targets brain regions related to the disorder, and mindfulness-based treatments. In the context of the TRR SFB 265 C04 “Mindfulness-based relapse prevention as an addition to rtfMRI NFB intervention for patients with Alcohol Use Disorder (MiND)” study, both interventions will be combined to a state-of-the art intervention that will use mindfulness-based relapse prevention to improve the efficacy of a real-time neurofeedback intervention targeting the ventral striatum, which is a brain region centrally involved in cue-reactivity to alcohol-related stimuli. Methods/design After inclusion, N = 88 patients will be randomly assigned to one of four groups. Two of those groups will receive mindfulness-based relapse prevention. All groups will receive two fMRI sessions and three real-time neurofeedback sessions in a double-blind manner and will regulate either the ventral striatum or the auditory cortex as a control region. Two groups will additionally receive five sessions of mindfulness-based relapse prevention prior to the neurofeedback intervention. After the last fMRI session, the participants will be followed-up monthly for a period of 3 months for an assessment of the relapse rate and clinical effects of the intervention. Discussion The results of this study will give further insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback interventions for the treatment of Alcohol Use Disorder. Additionally, the study will provide further insight on neurobiological changes in the brain caused by the neurofeedback intervention as well as by the mindfulness-based relapse prevention. The outcome might be useful to develop new treatment approaches targeting mechanisms of Alcohol Use Disorder with the goal to reduce relapse rates after discharge from the hospital. Trial registration This trial is pre-registered at clinicaltrials.gov (trial identifier: NCT04366505 ; WHO Universal Trial Number (UTN): U1111–1250-2964). Registered 30 March 2020, published 29 April 2020.

Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions.

Predictive coding models of brain processing propose that top-down cortical signals promote efficient neural signaling by carrying predictions about incoming sensory information. These “priors” serve to constrain bottom-up signal propagation where prediction errors are carried via feedforward mechanisms. Depression, traditionally viewed as a disorder characterized by negative cognitive biases, is associated with disrupted reward prediction error encoding and signaling. Accumulating evidence also suggests that depression is characterized by impaired local and long-range prediction signaling across multiple sensory domains. This review highlights the electrophysiological and neuroimaging evidence for disrupted predictive processing in depression. The discussion is framed around the manner in which disrupted generative predictions about the sensorium could lead to depressive symptomatology, including anhedonia and negative bias. In particular, the review focuses on studies of sensory deviance detection and reward processing, highlighting research evidence for both disrupted generative predictions and prediction error signaling in depression. The role of the monoaminergic and glutamatergic systems in predictive coding processes is also discussed. This review provides a novel framework for understanding depression using predictive coding principles and establishes a foundational roadmap for potential future research.

Background: Growing evidence points towards dysfunction of the ventral striatum as a neural substrate of motivational impairments in schizophrenia. Ventral striatal activity during reward anticipation is generally reduced in patients with schizophrenia and specifically correlates with apathy. However, little is known about the cortico-striatal functional connectivity in patients with schizophrenia during reward anticipation and its relation to negative symptoms. Objectives: The aim of this study was to identify categorical group differences in ventral striatal functional connectivity during reward anticipation between patients with schizophrenia and healthy controls, and dimensional associations between cortico-striatal functional connectivity and negative symptom severity. Method: A total of 40 patients with schizophrenia (10 females) and 33 healthy controls (8 females) were included from two previously published studies. All participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI. Functional connectivity was assessed using psychophysical interactions (PPI) with the left and right ventral striatum as seeds and the contrast [High Reward Anticipation – No Reward Anticipation]. Negative symptoms were assessed using the Brief Negative Symptom Scale. Results: Compared to controls, patients with schizophrenia showed increased functional connectivity between the left ventral striatum and the left precuneus and right parahippocampal gyrus, two hubs of the default mode network (cluster-level threshold: FWE, p

The ventral striatum is implicated in the affective processing of reward, which can be divided into a motivational and a hedonic component. Here, we examined whether these two components rely on distinct neural substrates within the ventral striatum in humans (11 females and 13 males). We used a high-resolution fMRI protocol targeting the ventral striatum combined with a pavlovian-instrumental task and a hedonic reactivity task. Both tasks involved an olfactory reward, thereby allowing us to measure pavlovian-triggered motivation and sensory pleasure for the same reward within the same participants. Our findings show that different subregions of the ventral striatum are dissociable in their contributions to the motivational versus the hedonic component of the affective processing of reward. Parsing the neural mechanisms of the interplay between pavlovian incentive and hedonic processes may have important implications for understanding compulsive rewardseeking behaviors such as addiction, binge eating, or gambling. [ABSTRACT FROM AUTHOR]

The locus coeruleus (LC) is a brainstem structure that sends widespread efferent projections throughout the mammalian brain. The LC constitutes the major source of noradrenaline (NE), a modulatory neurotransmitter that is crucial for fundamental brain functions such as arousal, attention, and cognitive control. This role of the LC-NE is traditionally not believed to reflect functional influences on the frontoparietal network or the striatum, but recent advances in chemogenetic manipulations of the rodent brain have challenged this notion. However, demonstrations of LC-NE functional connectivity with these areas in the human brain are surprisingly sparse. Here, we close this gap. Using an established emotional stroop task, we directly compared trials requiring response conflict control with trials that did not require this, but were matched for visual stimulus properties, response modality, and controlled for pupil dilation differences across both trial types. We found that LC-NE functional coupling with the parietal cortex and regions of the striatum is substantially enhanced during trials requiring response conflict control. Crucially, the strength of this functional coupling was directly related to individual reaction time differences incurred by conflict resolution. Our data concur with recent rodent findings and highlight the importance of converging evidence between human and nonhuman neurophysiology to further understand the neural systems supporting adaptive and maladaptive behavior in health and disease. [ABSTRACT FROM AUTHOR]

Predictive coding models of brain processing propose that top-down cortical signals promote efficient neural signaling by carrying predictions about incoming sensory information. These "priors" serve to constrain bottom-up signal propagation where prediction errors are carried via feedforward mechanisms. Depression, traditionally viewed as a disorder characterized by negative cognitive biases, is associated with disrupted reward prediction error encoding and signaling. Accumulating evidence also suggests that depression is characterized by impaired local and long-range prediction signaling across multiple sensory domains. This review highlights the electrophysiological and neuroimaging evidence for disrupted predictive processing in depression. The discussion is framed around the manner in which disrupted generative predictions about the sensorium could lead to depressive symptomatology, including anhedonia and negative bias. In particular, the review focuses on studies of sensory deviance detection and reward processing, highlighting research evidence for both disrupted generative predictions and prediction error signaling in depression. The role of the monoaminergic and glutamatergic systems in predictive coding processes is also discussed. This review provides a novel framework for understanding depression using predictive coding principles and establishes a foundational roadmap for potential future research. [ABSTRACT FROM AUTHOR]

Appropriate responding to threat and reward is essential to survival. The nucleus accumbens core (NAcc) is known to support and organize reward behavior. The NAcc is also necessary to fully discriminate threat and safety cues. To directly reveal NAcc threat firing, we recorded single-unit activity from seven female rats undergoing pavlovian fear discrimination. Rats fully discriminated danger, uncertainty, and safety cues, and most NAcc neurons showed the greatest firing change to danger and uncertainty. Heterogeneity in cue and reward firing led us to identify distinct functional populations. One NAcc population signaled threat, specifically decreasing firing to danger and uncertainty cues. A separate population signaled Bidirectional Valence, decreasing firing to the danger cue (negative valence), but increasing firing to reward (positive valence). The results reveal the NAcc to be a source of threat information and a more general valence hub. [ABSTRACT FROM AUTHOR]

Reward processing is important for understanding behavior in psychopathology. Opportunities to earn money activate the ventral striatum, as shown by the monetary incentive delay (MID) task. Anxiety conditions have been modeled by presenting shocks and startling sounds. To further investigate the co-occurrence of an anxiety condition and a rewarding stimulus, we modified the MID to include a sustained threat of scream. This study investigated neural patterns of the MID task with an uncertain threat of a startling scream. Forty-three young adults completed a functional MRI scan. The task included two conditions (scream and safe) and three cues (gain $5, gain $0, lose $5). Analyses included a whole brain, group analysis using a linear mixed-effects model and a paired t-test. The whole brain analysis revealed a main effect of cue, with increased ventral striatal activation (F2,210 = 58.8, p < 0.001) during cues to gain or lose $5. We observed a main effect of condition during cue presentation, such that bilateral insula and putamen activation was diminished (p < 0.001) in the scream versus the safe condition. A t-test of condition showed increased activation during threat blocks in the insula and putamen. A time course graph revealed that activation in the insula and putamen responded similarly to incentive but had an overall elevation during the scream condition. These results replicated expected activation in reward and in the setting of uncertain threat. Our results show that uncertain threat increases the magnitude of activation in the dorsal striatum. [ABSTRACT FROM AUTHOR]

Altered ventral striatal (vST) activation to reward expectancy is a well-established intermediate phenotype for psychiatric disorders, specifically schizophrenia (SZ). Preclinical research suggests that striatal alterations are related to a reduced inhibition by the hippocampal formation, but its role in human transdiagnostic reward-network dysfunctions is not well understood. We performed functional magnetic resonance imaging during reward processing in 728 individuals including healthy control subjects (n = 396), patients (SZ: n = 46; bipolar disorder: n = 45; major depressive disorder: n = 60), and unaffected first-degree relatives (SZ: n = 46; bipolar disorder: n = 50; major depressive disorder: n = 85). We assessed disorder-specific differences in functional vST-hippocampus coupling and transdiagnostic associations with dimensional measures of positive, negative, and cognitive symptoms. We also probed the genetic underpinning using polygenic risk scores for SZ in a subset of healthy participants (n = 295). Functional vST-hippocampus coupling was 1) reduced in patients with SZ and bipolar disorder (p FWE <.05, small-volume corrected [SVC]); 2) associated transdiagnostically to dimensional measures of positive (p FWE =.01, SVC) and cognitive (p FWE =.02, SVC), but not negative, (p FWE >.05, SVC) symptoms; and 3) reduced in first-degree relatives of patients with SZ (p FWE =.017, SVC) and linked to the genetic risk for SZ in healthy participants (p =.035). We provide evidence that reduced vST-hippocampus coupling during reward processing is an endophenotype for SZ linked to positive and cognitive symptoms, supporting current preclinical models of the emergence of psychosis. Moreover, our data indicate that vST-hippocampus coupling is familial and linked to polygenic scores for SZ, supporting the use of this measure as an intermediate phenotype for psychotic disorders. [ABSTRACT FROM AUTHOR]

Failure to sustain positive affect over time is a hallmark of depression and other psychopathologies, but the mechanisms supporting the ability to sustain positive emotional responses are poorly understood. Here, we investigated the neural correlates associated with the persistence of positive affect in the real world by conducting two experiments in humans: an fMRI task of reward responses and an experience-sampling task measuring emotional responses to a reward obtained in the field. The magnitude of DLPFC engagement to rewards administered in the laboratory predicted reactivity of real-world positive emotion following a reward administered in the field. Sustained ventral striatum engagement in the laboratory positively predicted the duration of real-world positive emotional responses. These results suggest that common pathways are associated with the unfolding of neural processes over seconds and with the dynamics of emotions experienced over minutes. Examining such dynamics may facilitate a better understanding of the brain-behavior associations underlying emotion. Significance statement: How real-world emotion, experienced over seconds, minutes, and hours, is instantiated in the brain over the course of milliseconds and seconds is unknown. We combined a novel, real-world experience-sampling task with fMRI to examine how individual differences in real-world emotion, experienced over minutes and hours, is subserved by affective neurodynamics of brain activity over the course of seconds. When winning money in the real world, individuals sustaining positive emotion the longest were those with the most prolonged ventral striatal activity. These results suggest that common pathways are associated with the unfolding of neural processes over seconds and with the dynamics of emotions experienced over minutes. Examining such dynamics may facilitate a better understanding of the brain-behavior associations underlying emotion.

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.

Early life stress – including experience of child maltreatment, neglect, separation from or loss of a parent, and other forms of adversity – increases lifetime risk of mood, anxiety, and substance use disorders. A major component of this risk may be early life stress-induced alterations in motivation and reward processing, mediated by changes in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here, we review evidence of the impact of early life stress on reward circuit structure and function from human and animal models, with a focus on the NAc. We then connect these results to emerging theoretical models about the indirect and direct impacts of early life stress on reward circuit development. Through this review and synthesis, we aim to highlight open research questions and suggest avenues of future study in service of basic science, as well as applied insights. Understanding how early life stress alters reward circuit development, function, and motivated behaviors is a critical first step toward developing the ability to predict, prevent, and treat stress-related psychopathology spanning mood, anxiety, and substance use disorders.

The endocannabinoid and orexin neuromodulatory systems serve key roles in many of the same biological functions such as sleep, appetite, pain processing, and emotional behaviors related to reward. The type 1 cannabinoid receptor (CB1R) and both subtypes of the orexin receptor, orexin receptor type 1 (OX1R) and orexin receptor type 2 (OX2R) are not only expressed in the same brain regions modulating these functions, but physically interact as heterodimers in recombinant and neuronal cell cultures. In the current study, male and female C57BL/6 mice were co-treated with the cannabinoid receptor agonist CP55,940 and either the OX2R antagonist TCS-OX2-29 or the dual orexin receptor antagonist (DORA) TCS-1102. Mice were then evaluated for catalepsy, body temperature, thermal anti-nociception, and locomotion, after which their brains were collected for receptor colocalization analysis. Combined treatment with the DORA TCS-1102 and CP55,940 potentiated catalepsy more than CP55,940 alone, but this effect was not observed for changes in body temperature, nociception, locomotion, or via selective OX2R antagonism. Co-treatment with CP55,940 and TCS-1102 also led to increased CB1R-OX1R colocalization in the ventral striatum. This was not seen following co-treatment with TCS-OX2-29, nor in CB1R-OX2R colocalization. The magnitude of effects following co-treatment with CP55,940 and either the DORA or OX2R-selective antagonist was greater in males than females. These data show that CB1R-OX1R colocalization in the ventral striatum underlies cataleptic additivity between CP55,940 and the DORA TCS-1102. Moreover, cannabinoid-orexin receptor interactions are sex-specific with regards to brain region and functionality. Physical or molecular interactions between these two systems may provide valuable insight into drug-drug interactions between cannabinoid and orexin drugs for the treatment of insomnia, pain, and other disorders. [ABSTRACT FROM AUTHOR]

• Depression is associated with abnormal responses to positive and negative feedback. • On a learning task, patients with depression were sensitive to negative information. • Depressed patients had a reduced brain response in the striatum to positive outcomes. • Responses to negative outcomes were not reduced in the striatum. • Findings provide evidence for a neural mechanism for abnormal learning in depression. Major depressive disorder (MDD) is characterized by behavioral and neural abnormalities in processing both rewarding and aversive stimuli, which may impact motivational and affective symptoms. Learning paradigms have been used to assess reinforcement encoding abnormalities in MDD and their association with dysfunctional incentive-based behavior, but how the valence and context of information modulate this learning is not well understood. To address these gaps, we examined responses to positive and negative reinforcement across multiple temporal phases of information processing. While undergoing functional magnetic resonance imaging (fMRI), 47 participants (23 unmedicated, predominantly medication-naïve participants with MDD and 24 demographically-matched HC participants) completed a probabilistic, feedback-based reinforcement learning task that allowed us to separate neural activation during motor response (choice) from reinforcement feedback and monetary outcome across two independent conditions: pursuing gains and avoiding losses. In the gain condition, MDD participants showed overall blunted learning responses (prediction error) in the dorsal striatum when receiving monetary outcome, and reduced responses in ventral striatum for positive, but not negative, prediction error. The MDD group showed enhanced sensitivity to negative information, and symptom severity was associated with better behavioral performance in the loss condition. These findings suggest that striatal responses during learning are abnormal in individuals with MDD but vary with the valence of information. [ABSTRACT FROM AUTHOR]

Deep brain stimulation is a promising therapeutic approach for patients with treatment-resistant obsessive-compulsive disorder, a condition linked to abnormalities in corticobasal ganglia networks. Effective targets are placed in one of four subcortical areas with the goal of capturing prefrontal, anterior cingulate, and basal ganglia connections linked to the limbic system. These include the anterior limb of the internal capsule, the ventral striatum, the subthalamic nucleus, and a midbrain target. The goal of this review is to examine these 4 targets with respect to the similarities and differences of their connections. Following a review of the connections for each target based on anatomic studies in nonhuman primates, we examine the accuracy of diffusion magnetic resonance imaging tractography to replicate those connections in nonhuman primates, before evaluating the connections in the human brain based on diffusion magnetic resonance imaging tractography. Results demonstrate that the four targets generally involve similar connections, all of which are part of the internal capsule. Nonetheless, some connections are unique to each site. Delineating the similarities and differences across targets is a critical step for evaluating and comparing the effectiveness of each and how circuits contribute to the therapeutic outcome. It also underscores the importance that the terminology used for each target accurately reflects its position and its anatomic connections, so as to enable comparisons across clinical studies and for basic scientists to probe mechanisms underlying deep brain stimulation. [ABSTRACT FROM AUTHOR]

Deep brain stimulation of the nucleus accumbens, ventral striatum, or internal capsule region has shown a 45%–60% response rate in adults with severe treatment-refractory obsessive-compulsive disorder, regardless of which target is used. We sought to improve the effectiveness of deep brain stimulation by placing the electrode along a trajectory including these 3 targets, enabling a change of stimulation site depending on the patient's response. This study used the medical records of 14 patients from 4 different Spanish institutions: 7 from the Hospital Universitario La Princesa, 3 from the Hospital Universitario Central de Asturias, 2 from Hospital Universitario Fundación Jiménez Díaz, and 2 from Hospital Universitari Son Espases. All patients were operated on under the same protocol. Qualitative and quantitative data were collected. Of 14 patients, 11 showed significant improvement in obsessive-compulsive disorder symptoms, as evident in a reduction ≥35% in Yale-Brown Obsessive Compulsive Scale scores following stimulation relative to preoperative scores. Seven patients responded to stimulation at the nucleus accumbens (the first area we set for stimulation), whereas 4 patients needed to have the active contact switched to the internal capsule to benefit from stimulation. Deep brain stimulation of the nucleus accumbens, internal capsule, and ventral striatum significantly benefited our cohort of patients with medication-resistant obsessive-compulsive disorder. Electrode insertion through the 3 main targets might confer additional therapeutic efficacy. [ABSTRACT FROM AUTHOR]