scholarly journals Medial forebrain bundle structure is linked to human impulsivity

2020 ◽  
Vol 6 (38) ◽  
pp. eaba4788 ◽  
Author(s):  
Kelly H. MacNiven ◽  
Josiah K. Leong ◽  
Brian Knutson
Keyword(s):  
Comparative Research ◽  
Medial Forebrain Bundle ◽  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Stimulant Use ◽  
Motivated Behavior ◽  
Trait Impulsivity ◽  
Structural Coherence ◽  
Midbrain Dopamine ◽  
Bundle Structure

Comparative research indicates that projections from midbrain dopamine nuclei [including the ventral tegmental area (VTA)] to the ventral striatum [including the nucleus accumbens (NAcc)] critically support motivated behavior. Using diffusion-weighted imaging and probabilistic tractography in humans, we characterized the trajectory and structure of two tracts connecting the VTA and NAcc, as well as others connecting the substantia nigra and dorsal striatum. Decreased structural coherence of an inferior VTA–NAcc tract was primarily and replicably associated with increased trait impulsivity and also distinguished individuals with a stimulant use disorder from healthy controls. These findings suggest that decreased coherence of the inferior VTA–NAcc tract is associated with increased impulsivity in humans and identify a previously uncharacterized structural target for diagnosing disorders marked by impulsivity.

scholarly journals Cue-reactivity in the ventral striatum characterizes heavy cannabis use, whereas reactivity in the dorsal striatum mediates dependent use

2019 ◽  
Author(s):  
Xinqi Zhou ◽  
Kaeli Zimmermann ◽  
Fei Xin ◽  
Weihua Zhao ◽  
Roelinka Derckx ◽  
...  
Keyword(s):  
Drug Use ◽  
Ventral Striatum ◽  
Reference Group ◽  
Cue Reactivity ◽  
Dorsal Striatum ◽  
Imaging Study ◽  
Magnetic Resonance Imaging Study ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Trait Impulsivity

AbstractBackgroundAnimal models of addiction suggest that the transition from incentive-driven to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue-control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and cue-reactivity in striatal circuits, however, these studies were not able to separate addiction-related from exposure-related adaptations.MethodsTo differentiate the adaptive changes, the present functional magnetic resonance imaging study examined behavioral and neural cue-reactivity in dependent (n = 18) and non-dependent (n = 20) heavy cannabis users and a non-using reference group (n = 44).ResultsIrrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striato-frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal-striatal reactivity and decreased striato-limbic coupling during cue-exposure. An exploratory analysis revealed that higher ventral caudate cue-reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in non-dependent users.ConclusionsTogether the present findings suggest that an incentive sensitization of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism

2020 ◽  
Author(s):  
Owen Y Chao ◽  
Salil S Pathak ◽  
Hao Zhang ◽  
Nathan Dunaway ◽  
Jay-Shake Li ◽  
...  
Keyword(s):  
Fragile X ◽  
Glutamate Transporter ◽  
Dorsal Striatum ◽  
Autism Spectrum ◽  
Acid Decarboxylase ◽  
Therapeutic Effects ◽  
Spatial Coupling ◽  
Motivated Behavior ◽  
Object Based ◽  
Glutamate Transporter 1

Abstract The dopamine (DA) system has a profound impact on reward-motivated behavior and is critically involved in neurodevelopmental disorders, such as autism spectrum disorder (ASD). Although DA defects are found in autistic patients, it is not well defined how the DA pathways are altered in ASD and whether DA can be utilized as a potential therapeutic agent for ASD. To this end, we employed a phenotypic and a genetic ASD model, i.e., Black and Tan BRachyury T+Itpr3tf/J (BTBR) mice and Fragile X Mental Retardation 1 knockout (Fmr1-KO) mice, respectively. Immunostaining of tyrosine hydroxylase (TH) to mark dopaminergic neurons revealed an overall reduction in the TH expression in the substantia nigra, ventral tegmental area and dorsal striatum of BTBR mice, as compared to C57BL/6J wild-type ones. In contrast, Fmr1-KO animals did not show such an alteration but displayed abnormal morphology of TH-positive axons in the striatum with higher “complexity” and lower “texture”. Both strains exhibited decreased expression of striatal dopamine transporter (DAT) and increased spatial coupling between vesicular glutamate transporter 1 (VGLUT1, a label for glutamatergic terminals) and TH signals, while GABAergic neurons quantified by glutamic acid decarboxylase 67 (GAD67) remained intact. Intranasal administration of DA rescued the deficits in non-selective attention, object-based attention and social approaching of BTBR mice, likely by enhancing the level of TH in the striatum. Application of intranasal DA to Fmr1-KO animals alleviated their impairment of social novelty, in association with reduced striatal TH protein. These results suggest that although the DA system is modified differently in the two ASD models, intranasal treatment with DA effectively rectifies their behavioral phenotypes, which may present a promising therapy for diverse types of ASD.

Differential Modulation by Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3388-3396 ◽  
Author(s):  
J. Russel Keath ◽  
Michael P. Iacoviello ◽  
Lindy E. Barrett ◽  
Huibert D. Mansvelder ◽  
Daniel S. McGehee
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Synaptic Modulation ◽  
Afferent Projections ◽  
Ventral Tegmental ◽  
Midbrain Dopamine ◽  
Da Release

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where α7 nAChRs enhance glutamate inputs and non-α7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.

scholarly journals Neural population dynamics underlying expected value computation

2020 ◽  
Author(s):  
Hiroshi Yamada ◽  
Yuri Imaizumi ◽  
Masayuki Matsumoto
Keyword(s):  
Ventral Striatum ◽  
Temporal Dynamics ◽  
Dorsal Striatum ◽  
Expected Value ◽  
Economic Behavior ◽  
Neural Dynamics ◽  
Neural Population ◽  
Integrative Process ◽  
Expected Values ◽  
The Brain

AbstractComputation of expected values, i.e., probability times magnitude, seems to be a dynamic integrative process performed in the brain for efficient economic behavior. However, neural dynamics underlying this computation remain largely unknown. We examined (1) whether four core reward-related regions detect and integrate the probability and magnitude cued by numerical symbols and (2) whether these regions have distinct dynamics in the integrative process. Extractions of mechanistic structure of neural population signal demonstrated that expected-value signals simultaneously arose in central part of orbitofrontal cortex (cOFC, area 13m) and ventral striatum (VS). These expected-value signals were incredibly stable in contrast to weak and/or fluctuated signals in dorsal striatum and medial OFC. Notably, temporal dynamics of these stable expected-value signals were unambiguously distinct: sharp and gradual signal evolutions in cOFC and VS, respectively. These intimate dynamics suggest that cOFC and VS compute the expected-values with unique time constants, as distinct, partially overlapping processes.

scholarly journals Shared striatal activity in decisions to satisfy curiosity and hunger at the risk of electric shocks

2018 ◽  
Author(s):  
Johnny King L Lau ◽  
Hiroki Ozono ◽  
Kei Kuratomi ◽  
Asuka Komiya ◽  
Kou Murayama
Keyword(s):  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Neural Mechanisms ◽  
Instrumental Value ◽  
Motivational Effect ◽  
Enhanced Activity ◽  
Electric Shocks ◽  
Desirable Feature

AbstractCuriosity is often portrayed as a desirable feature of human faculty. However, curiosity may come at a cost that sometimes puts people in a harmful situation. Here, with a set of behavioural and neuroimaging experiments using stimuli that strongly trigger curiosity (e.g., magic tricks), we examined the psychological and neural mechanisms underlying the motivational effect of curiosity. We consistently demonstrated that across different samples, people were indeed willing to gamble, subjecting themselves to physical risks (i.e. electric shocks) in order to satisfy their curiosity for trivial knowledge that carries no apparent instrumental value. Also, this influence of curiosity shares common neural mechanisms with that of extrinsic incentives (i.e. hunger for food). In particular, we showed that acceptance (compared to rejection) of curiosity/incentive-driven gambles was accompanied by enhanced activity in the ventral striatum (when curiosity was elicited), which extended into the dorsal striatum (when participants made a decision).

scholarly journals The tubular striatum and nucleus accumbens distinctly represent reward-taking and seeking

2020 ◽  
Author(s):  
Katherine N. Wright ◽  
Daniel W Wesson
Keyword(s):  
Nucleus Accumbens ◽  
Ventral Striatum ◽  
Neural Representation ◽  
Single Unit Activity ◽  
Self Administration ◽  
Reward Seeking ◽  
Motivated Behavior ◽  
Behavioral Paradigm ◽  
Motivated Behaviors ◽  
Goal Directed Behavior

The ventral striatum regulates motivated behaviors which are essential for survival. The ventral striatum contains both the nucleus accumbens (NAc), which is well established to contribute to motivated behavior, and the adjacent tubular striatum (TuS), which is poorly understood in this context. We reasoned that these ventral striatal subregions may be uniquely specialized in their neural representation of goal-directed behavior. To test this, we simultaneously examined TuS and NAc single-unit activity as male mice engaged in a sucrose self-administration task, which included extinction and cue-induced reinstatement sessions. While background levels of activity were comparable between regions, more TuS neurons were recruited upon reward-taking, and among recruited neurons, TuS neurons displayed greater changes in their firing during reward-taking and extinction than those in the NAc. Conversely, NAc neurons displayed greater changes in their firing during cue-reinstated reward-seeking. Interestingly, at least in the context of this behavioral paradigm, TuS neural activity predicted reward-seeking whereas NAc activity did not. Together, by directly comparing their dynamics in several behavioral contexts, this work reveals that the NAc and TuS ventral striatum subregions distinctly represent reward-taking and seeking.

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