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2.
Nature ; 612(7941): 739-747, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36517598

RESUMO

Exercise exerts a wide range of beneficial effects for healthy physiology1. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise-induced neurochemical changes in the brain. Here, we report on the discovery of a gut-brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome-dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1-expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut-derived interoceptive circuits and provide a microbiome-dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut-derived signals to the brain may enhance the motivation for exercise.


Assuntos
Eixo Encéfalo-Intestino , Dopamina , Exercício Físico , Microbioma Gastrointestinal , Motivação , Corrida , Animais , Camundongos , Encéfalo/citologia , Encéfalo/metabolismo , Dopamina/metabolismo , Endocanabinoides/antagonistas & inibidores , Endocanabinoides/metabolismo , Células Receptoras Sensoriais/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Microbioma Gastrointestinal/fisiologia , Exercício Físico/fisiologia , Exercício Físico/psicologia , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/psicologia , Modelos Animais , Humanos , Estriado Ventral/citologia , Estriado Ventral/metabolismo , Corrida/fisiologia , Corrida/psicologia , Recompensa , Individualidade
3.
J Neurosci ; 42(41): 7833-7847, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36414013

RESUMO

Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although recent studies implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, here we revealed coexisting and opposite morphologic and functional alterations in the dorsostriatal direct and indirect pathways, and such alterations in these two pathways were found to be responsible, respectively, for the two abovementioned different autism-like behaviors exhibited by male mice prenatally exposed to valproate. The alteration in direct pathway was characterized by a potentiated state of basal activity, with impairment in transient responsiveness of D1-MSNs during social exploration. Concurrent alteration in indirect pathway was a depressed state of basal activity, with enhancement in transient responsiveness of D2-MSNs during repetitive behaviors. A causal relationship linking such differential alterations in these two pathways to the coexistence of these two autism-like behaviors was demonstrated by the cell type-specific correction of abnormal basal activity in the D1-MSNs and D2-MSNs of valproate-exposed mice. The findings support those differential alterations in two striatal pathways mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations.SIGNIFICANCE STATEMENT Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although a number of recent studies have implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, but social behaviors need to be processed by a series of actions, and repetitive behaviors, especially the high-order repetitive behaviors such as restrictive interests, have its scope to cognitive and emotional domains. The current study, for the first time, revealed that prenatal valproate exposure induced coexisting and differential alterations in the dorsomedial striatal direct and indirect pathways, and that these alterations mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations to address the behavioral abnormalities.


Assuntos
Transtorno Autístico , Estriado Ventral , Camundongos , Animais , Masculino , Transtorno Autístico/metabolismo , Ácido Valproico , Comportamento Social , Estriado Ventral/metabolismo
4.
Psychiatry Res Neuroimaging ; 327: 111561, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36334392

RESUMO

Altered reward sensitivity has been proposed to underlie symptoms of attention deficit hyperactivity disorder (ADHD). Functional magnetic resonance imaging (fMRI) studies have reported hypoactivation to reward-predicting cues in the ventral striatum among individuals with ADHD, using experimental designs with and without behavioral response requirements. These studies have typically used monetary incentives as rewards; however, it is unclear if these findings extend to other reward types. The current study examined striatal responses to anticipation and delivery of both affiliative and food reward images using a classical conditioning paradigm. Data from 20 typically developing young adults, and 20 individuals diagnosed with ADHD were included in a region-of-interest analysis for a priori striatal regions. Consistent with findings from studies using monetary rewards, individuals with ADHD showed decreased activation to cues predicting affiliative rewards in the bilateral ventral and dorsal striatum and increased activation to the delivery of affiliative rewards in the ventral striatum. No group differences were found in striatal responses to food reward cues or images. These results suggest hyposensitivity to reward-predicting cues in ADHD extends to affiliative rewards, with important implications for understanding and managing the learning and social functioning of those with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estriado Ventral , Adulto Jovem , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Recompensa , Estriado Ventral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Motivação
5.
Cortex ; 156: 106-125, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36240722

RESUMO

Functional magnetic resonance imaging (fMRI) studies on the dynamic representation of task content focus preferentially on the cerebral cortex. However, neurophysiological studies report coding of task-relevant features also by neurons in the striatum, suggesting basal ganglia involvement in cognitive decision-making. Here we use fMRI data to show that also in humans the striatum is an integrated part of the cognitive brain network. Twelve participants performed 3 cognitive tasks in the scanner, i.e., the Eriksen flanker task, a 2-back matching spatial working memory task, and a response scheme switching task. First, we use region of interest-based multivariate pattern classification to demonstrate that each task reliably induces a unique activity pattern in the striatum and in the lateral prefrontal cortex. We show that the three tasks can also be distinguished in putamen, caudate nucleus and ventral striatum alone. We additionally establish that the contribution of striatum to cognition is not sensitive to habituation or learning. Secondly, we use voxel-to-voxel functional connectivity to establish that voxels in the lateral prefrontal cortex and in the striatum that prefer the same task show significantly stronger functional coupling than voxel pairs in these remote structures that prefer different tasks. These results suggest that striatal neurons form subnetworks with cognition-related regions of the prefrontal cortex. These remote neuron populations are interconnected via functional couplings that exceed the time of execution of the specific tasks.


Assuntos
Córtex Pré-Frontal , Estriado Ventral , Humanos , Vias Neurais , Córtex Pré-Frontal/fisiologia , Corpo Estriado , Núcleo Caudado , Putamen , Imageamento por Ressonância Magnética
6.
Psychopharmacology (Berl) ; 239(10): 3313-3323, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36094619

RESUMO

The pathophysiology of schizophrenia involves abnormal reward processing, thought to be due to disrupted striatal and dopaminergic function. Consistent with this hypothesis, functional magnetic resonance imaging (fMRI) studies using the monetary incentive delay (MID) task report hypoactivation in the striatum during reward anticipation in schizophrenia. Dopamine neuron activity is modulated by striatal GABAergic interneurons. GABAergic interneuron firing rates, in turn, are related to conductances in voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels, suggesting that targeting Kv3.1/3.2 could augment striatal function during reward processing. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on striatal activation in patients with schizophrenia, using the MID task. Each participant completed the MID during fMRI scanning on two occasions: once at baseline, and again following either 4 weeks of AUT00206 or placebo treatment. We found a significant inverse relationship at baseline between symptom severity and reward anticipation-related neural activation in the right associative striatum (r = -0.461, p = 0.035). Following treatment with AUT00206, there was a significant increase in reward anticipation-related activation in the left associative striatum (t(13) = 4.23, peak-level p(FWE) < 0.05)), but no significant effect in the ventral striatum. This provides preliminary evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address reward-related striatal abnormalities in schizophrenia.


Assuntos
Esquizofrenia , Estriado Ventral , Humanos , Imageamento por Ressonância Magnética , Recompensa , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Canais de Potássio Shaw , Estriado Ventral/fisiologia
7.
Addict Biol ; 27(5): e13210, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36001435

RESUMO

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.


Assuntos
Comportamento Aditivo , Estriado Ventral , Jogos de Vídeo , Comportamento Aditivo/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico/métodos , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imunoglobulina D , Internet , Transtorno de Adição à Internet , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Estriado Ventral/diagnóstico por imagem
8.
Transl Psychiatry ; 12(1): 300, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902559

RESUMO

Although altered reward sensitivity has been observed in individuals with bipolar disorder (BD), the brain function findings related to reward processing remain unexplored and inconsistent. This meta-analysis aimed to identify brain activation alterations underlying reward anticipation in BD. A systematic literature research was conducted to identify fMRI studies of reward-relevant tasks performed by BD individuals. Using Anisotropic Effect Size Signed Differential Mapping, whole-brain and ROI of the ventral striatum (VS) coordinate-based meta-analyses were performed to explore brain regions showing anomalous activation in individuals with BD compared to healthy controls (HC), respectively. A total of 21 studies were identified in the meta-analysis, 15 of which were included in the whole-brain meta-analysis and 17 in the ROI meta-analysis. The whole-brain meta-analysis revealed hypoactivation in the bilateral angular gyrus and right inferior frontal gyrus during reward anticipation in individuals with BD compared to HC. No significant activation differences were observed in bilateral VS between two groups by whole-brain or ROI-based meta-analysis. Individuals with BD type I and individuals with euthymic BD showed altered activation in prefrontal, angular, fusiform, middle occipital gyrus, and striatum. Hypoactivation in the right angular gyrus was positively correlated with the illness duration of BD. The present study reveals the potential neural mechanism underlying impairment in reward anticipation in BD. Some clinical features such as clinical subtype, mood state, and duration of illness confound the underlying neurobiological abnormality reward anticipation in BD. These findings may have implications for identifying clinically relevant biomarkers to guide intervention strategies for BD.


Assuntos
Transtorno Bipolar , Estriado Ventral , Antecipação Psicológica/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Recompensa , Estriado Ventral/diagnóstico por imagem
9.
Am J Psychiatry ; 179(7): 458-469, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35775159

RESUMO

Anhedonia-the loss of pleasure or lack of reactivity to pleasurable stimuli-remains a formidable treatment challenge across neuropsychiatric disorders. In major depressive disorder, anhedonia has been linked to poor disease course, worse response to psychological, pharmacological, and neurostimulation treatments, and increased suicide risk. Moreover, although some neural abnormalities linked to anhedonia normalize after successful treatment, several persist-for example, blunted activation of the ventral striatum to reward-related cues and reduced functional connectivity involving the ventral striatum. Critically, some of these abnormalities have also been identified in unaffected, never-depressed children of parents with major depressive disorder and have been found to prospectively predict the first onset of major depression. Thus, neural abnormalities linked to anhedonia may be promising targets for prevention. Despite increased appreciation of the clinical importance of anhedonia and its underlying neural mechanisms, important gaps remain. In this overview, the author first summarizes the extant knowledge about the pathophysiology of anhedonia, which may provide a road map toward novel treatment and prevention strategies, and then highlights several priorities to facilitate clinically meaningful breakthroughs. These include a need for 1) appropriately controlled clinical trials, especially those embracing an experimental therapeutics approach to probe target engagement; 2) novel preclinical models relevant to anhedonia, with stronger translational value; and 3) clinical scales that incorporate neuroscientific advances in our understanding of anhedonia. The author concludes by highlighting important future directions, emphasizing the need for an integrated, collaborative, cross-species, and multilevel approach to tackling anhedonic phenotypes.


Assuntos
Transtorno Depressivo Maior , Estriado Ventral , Anedonia/fisiologia , Transtorno Depressivo Maior/psicologia , Humanos , Imageamento por Ressonância Magnética , Recompensa
10.
Nat Commun ; 13(1): 3805, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778414

RESUMO

Optimal behavior requires interpreting environmental cues that indicate when to perform actions. Dopamine is important for learning about reward-predicting events, but its role in adapting to inhibitory cues is unclear. Here we show that when mice can earn rewards in the absence but not presence of an auditory cue, dopamine level in the ventral striatum accurately reflects reward availability in real-time over a sustained period (80 s). In addition, unpredictable transitions between different states of reward availability are accompanied by rapid (~1-2 s) dopamine transients that deflect negatively at the onset and positively at the offset of the cue. This Dopamine encoding of reward availability and transitions between reward availability states is not dependent on reward or activity evoked dopamine release, appears before mice learn the task and is sensitive to motivational state. Our findings are consistent across different techniques including electrochemical recordings and fiber photometry with genetically encoded optical sensors for calcium and dopamine.


Assuntos
Dopamina , Estriado Ventral , Animais , Sinais (Psicologia) , Dopamina/fisiologia , Camundongos , Núcleo Accumbens , Recompensa
11.
Nat Commun ; 13(1): 3305, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676281

RESUMO

Identifying the circuits responsible for cognition and understanding their embedded computations is a challenge for neuroscience. We establish here a hierarchical cross-scale approach, from behavioral modeling and fMRI in task-performing mice to cellular recordings, in order to disentangle local network contributions to olfactory reinforcement learning. At mesoscale, fMRI identifies a functional olfactory-striatal network interacting dynamically with higher-order cortices. While primary olfactory cortices respectively contribute only some value components, the downstream olfactory tubercle of the ventral striatum expresses comprehensively reward prediction, its dynamic updating, and prediction error components. In the tubercle, recordings reveal two underlying neuronal populations with non-redundant reward prediction coding schemes. One population collectively produces stabilized predictions as distributed activity across neurons; in the other, neurons encode value individually and dynamically integrate the recent history of uncertain outcomes. These findings validate a cross-scale approach to mechanistic investigations of higher cognitive functions in rodents.


Assuntos
Reforço Psicológico , Estriado Ventral , Animais , Córtex Cerebral , Imageamento por Ressonância Magnética , Camundongos , Tubérculo Olfatório , Recompensa , Estriado Ventral/diagnóstico por imagem
12.
Elife ; 112022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35708179

RESUMO

Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory input to the ventral striatal olfactory tubercle (OT) and its convergence with dense dopaminergic input to the OT could underlie this privileged form of associative memory, but how this process occurs is not well understood. We imaged the activity of the two canonical types of striatal neurons, expressing D1- or D2-type dopamine receptors, in the OT at cellular resolution while mice learned odor-outcome associations ranging from aversive to rewarding. D1 and D2 neurons both responded to rewarding and aversive odors. D1 neurons in the OT robustly and bidirectionally represented odor valence, responding similarly to odors predicting similar outcomes regardless of odor identity. This valence representation persisted even in the absence of a licking response to the odors and in the absence of the outcomes, indicating a true transformation of odor sensory information by D1 OT neurons. In contrast, D2 neuronal representation of the odor-outcome associations was weaker, contingent on a licking response by the mouse, and D2 neurons were more selective for odor identity than valence. Stimulus valence coding in the OT was modality-sensitive, with separate sets of D1 neurons responding to odors and sounds predicting the same outcomes, suggesting that integration of multimodal valence information happens downstream of the OT. Our results point to distinct representation of identity and valence of odor stimuli by D1 and D2 neurons in the OT.


Assuntos
Sinais (Psicologia) , Estriado Ventral , Animais , Camundongos , Neurônios/fisiologia , Odorantes , Tubérculo Olfatório/fisiologia , Receptores de Dopamina D2/metabolismo , Olfato/fisiologia , Estriado Ventral/metabolismo
13.
Soc Neurosci ; 17(4): 339-351, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35658812

RESUMO

Aggression occurs frequently and severely between rival groups. Although there has been much study into the psychological and socio-ecological determinants of intergroup aggression, the neuroscience of this phenomenon remains incomplete. To examine the neural correlates of aggression directed at outgroup (versus ingroup) targets, we recruited 35 healthy young male participants who were current or former students of the same university. While undergoing functional MRI, participants completed an aggression task against both an ingroup and an outgroup opponent in which their opponents repeatedly provoked them at varying levels and then participants could retaliate. Participants were then socially included and then excluded by two outgroup members and then completed the same aggression task against the same two opponents. Both before and after outgroup exclusion, aggression toward outgroup members was positively associated with activity in the ventral striatum during decisions about how aggressive to be toward their outgroup opponent. Aggression toward outgroup members was also linked to greater post-exclusion activity in the rostral and dorsal medial prefrontal cortex during provocation from their outgroup opponent. These altered patterns of brain activity suggest that frontostriatal mechanisms may play a significant role in motivating aggression toward outgroup members.


Assuntos
Agressão , Estriado Ventral , Agressão/psicologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal
14.
Neuropsychopharmacology ; 47(12): 2081-2089, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35752682

RESUMO

Dysregulation of frontal cortical inputs to the striatum is foundational in the neural basis of substance use disorder (SUD). Neuroanatomical and electrophysiological data increasingly show that striatal nodes receive appreciable input from numerous cortical areas, and that the combinational properties of these multivariate "connectivity profiles" play a predominant role in shaping striatal activity and function. Yet, how abnormal configuration of striatal connectivity profiles might contribute to SUD is unknown. Here, we implemented a novel "connectivity profile analysis" (CPA) approach using resting-state functional connectivity data to facilitate detection of different types of connectivity profile "misconfiguration" that may reflect distinct forms of aberrant circuit plasticity in SUD. We examined 46 nicotine-dependent smokers and 33 non-smokers and showed that both dorsal striatum (DS) and ventral striatum (VS) connectivity profiles with frontal cortex were misconfigured in smokers-but in doubly distinct fashions. DS misconfigurations were stable across sated and acute abstinent states (indicative of a "trait" circuit adaptation) whereas VS misconfigurations emerged only during acute abstinence (indicative of a "state" circuit adaptation). Moreover, DS misconfigurations involved abnormal connection strength rank order arrangement, whereas VS misconfigurations involved abnormal aggregate strength. We found that caudal ventral putamen in smokers uniquely displayed multiple types of connectivity profile misconfiguration, whose interactive magnitude was linked to dependence severity, and that VS misconfiguration magnitude correlated positively with withdrawal severity during acute abstinence. Findings underscore the potential for approaches that more aptly model the neurobiological composition of corticostriatal circuits to yield deeper insights into the neural basis of SUD.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Estriado Ventral , Mapeamento Encefálico , Corpo Estriado/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Nicotina , Putamen , Estriado Ventral/diagnóstico por imagem
15.
Neuroimage ; 258: 119398, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35724856

RESUMO

The default mode network (DMN) has been theorized to participate in a range of social, cognitive, and affective functions. Yet, previous accounts do not consider how the DMN contributes to other brain regions depending on psychological context, thus rendering our understanding of DMN function incomplete. We addressed this gap by applying a novel network-based psychophysiological interaction (nPPI) analysis to the reward task within the Human Connectome Project. We first focused on the task-evoked responses of the DMN and other networks involving the prefrontal cortex, including the executive control network (salience network) and the left and right frontoparietal networks. Consistent with a host of prior studies, the DMN exhibited a relative decrease in activation during the task, while the other networks exhibited a relative increase during the task. Next, we used nPPI analyses to assess whether these networks exhibit task-dependent changes in connectivity with other brain regions. Strikingly, we found that the experience of reward enhances task-dependent connectivity between the DMN and the ventral striatum, an effect that was specific to the DMN. Surprisingly, the strength of DMN-VS connectivity was correlated with personality characteristics relating to openness. Taken together, these results advance models of DMN by demonstrating how it contributes to other brain systems during task performance and how those contributions relate to individual differences.


Assuntos
Conectoma , Estriado Ventral , Encéfalo/fisiologia , Mapeamento Encefálico , Conectoma/métodos , Rede de Modo Padrão , Humanos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiologia , Recompensa , Estriado Ventral/diagnóstico por imagem
16.
Transl Psychiatry ; 12(1): 190, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523767

RESUMO

Alcohol Use Disorder (AUD) is a major contributor to global mortality and morbidity. Postmortem human brain tissue enables the investigation of molecular mechanisms of AUD in the neurocircuitry of addiction. We aimed to identify differentially expressed (DE) genes in the ventral and dorsal striatum between individuals with AUD and controls, and to integrate the results with findings from genome- and epigenome-wide association studies (GWAS/EWAS) to identify functionally relevant molecular mechanisms of AUD. DNA-methylation and gene expression (RNA-seq) data was generated from postmortem brain samples of 48 individuals with AUD and 51 controls from the ventral striatum (VS) and the dorsal striatal regions caudate nucleus (CN) and putamen (PUT). We identified DE genes using DESeq2, performed gene-set enrichment analysis (GSEA), and tested enrichment of DE genes in results of GWASs using MAGMA. Weighted correlation network analysis (WGCNA) was performed for DNA-methylation and gene expression data and gene overlap was tested. Differential gene expression was observed in the dorsal (FDR < 0.05), but not the ventral striatum of AUD cases. In the VS, DE genes at FDR < 0.25 were overrepresented in a recent GWAS of problematic alcohol use. The ARHGEF15 gene was upregulated in all three brain regions. GSEA in CN and VS pointed towards cell-structure associated GO-terms and in PUT towards immune pathways. The WGCNA modules most strongly associated with AUD showed strong enrichment for immune response and inflammation pathways. Our integrated analysis of multi-omics data sets provides further evidence for the importance of immune- and inflammation-related processes in AUD.


Assuntos
Alcoolismo , Estriado Ventral , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/genética , DNA , Humanos , Inflamação
17.
Am J Psychiatry ; 179(7): 470-481, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35582783

RESUMO

OBJECTIVE: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium. METHODS: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivityrw). The main analyses assessed associations of VS connectivityrw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations. RESULTS: Higher right VS connectivityrw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivityrw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivityrw and anhedonia emerged in the structural equation model: left VS connectivityrw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivityrw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivityrw did not predict low mood at any time point in the structural equation model. CONCLUSIONS: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivityrw in anhedonia but not in low mood.


Assuntos
Anedonia , Estriado Ventral , Adolescente , Depressão , Feminino , Humanos , Imageamento por Ressonância Magnética , Recompensa , Estriado Ventral/diagnóstico por imagem
18.
Neuroimage ; 256: 119267, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35504565

RESUMO

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.


Assuntos
Rede de Modo Padrão , Estriado Ventral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Rede de Modo Padrão/diagnóstico por imagem , Função Executiva , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Confiança , Estriado Ventral/diagnóstico por imagem , Adulto Jovem
19.
Curr Top Behav Neurosci ; 58: 111-127, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35397065

RESUMO

Anhedonia is a hallmark feature of depression and is highly prevalent among individuals with mood disorders. The history and neurobiology of anhedonia has been most extensively studied in the context of unipolar Major Depressive Disorder (MDD), with converging lines of evidence indicating that marked anhedonia heralds a more chronic and treatment-refractory illness course. Furthermore, findings from neuroimaging studies suggest that anhedonia in MDD is associated with aberrant reward-related activation in key brain reward regions, particularly blunted reward anticipation-related activation in the ventral striatum. However, the ongoing clinical challenge of treating anhedonia in the context of Bipolar Disorder (BD) also highlights important gaps in our understanding of anhedonia's prevalence, severity, and pathophysiology along the entire mood disorder spectrum. In addition, although current theoretical models posit a key role for reward hyposensitivity in BD depression, unlike studies in MDD, studies in BD do not clearly show evidence for reduced reward-related activation in striatal or other brain regions. Although further research is needed, the evidence to date hints at a divergent pathophysiology for anhedonia in unipolar and bipolar mood disorders, which, if better understood, could lead to significant improvements in the diagnosis and treatment of MDD and BD.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Estriado Ventral , Anedonia/fisiologia , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Recompensa
20.
Neuropharmacology ; 212: 109074, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35487273

RESUMO

Alcohol use disorder is a complex psychiatric disorder that can be modeled in rodents using a number of drinking paradigms. Drinking-in-the-dark (DID) is widely used to model the binge/intoxication stage of addiction, and chronic intermittent ethanol vapor procedures (CIE) are used to induce dependence and model withdrawal/negative affect induced escalation of drinking. We discuss experiments showing the ventral striatum (vStr) and extended amygdala (EA) are engaged in response to ethanol in rodents through c-Fos/Fos immunoreactivity studies. We also discuss experiments in rodents that span a wide variety of techniques where the function of vStr and EA structures are changed following DID or CIE, and the role of neurotransmitter and neuropeptide systems studies in these ethanol-related outcomes. We note where signaling systems converge across regions and paradigms and where there are still gaps in the literature. Dynorphin/κ-opioid receptor (KOR) signaling, as well as corticotropin releasing factor (CRF)/CRF receptor signaling were found to be important regulators of drinking behaviors across brain regions and drinking paradigms. Future research will require that females and a variety of rodent strains are used in preclinical experiments in order to strengthen the generalizability of findings and improve the likelihood of success for testing potential therapeutics in human laboratory studies.


Assuntos
Consumo de Bebidas Alcoólicas , Estriado Ventral , Tonsila do Cerebelo/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Etanol , Humanos , Receptores de Hormônio Liberador da Corticotropina , Estriado Ventral/metabolismo
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