25 research outputs found
Beta receptor-mediated modulation of the late positive potential in humans
RATIONALE
Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about the source of that modulation.
OBJECTIVES
The present study investigated whether beta-adrenergic receptors are involved in the generation of the LPP.
METHODS
We used a genetic individual differences approach (experiment 1) and a pharmacological manipulation (experiment 2) to test the hypothesis that the LPP is modulated by the activation of β-adrenergic receptors.
RESULTS
In experiment 1, we found that LPP amplitude depends on allelic variation in the β1-receptor gene polymorphism. In experiment 2, we found that LPP amplitude was modulated by the β-blocker propranolol in a direction dependent on subjects' level of trait anxiety: In participants with lower trait anxiety, propranolol led to a (nonsignificant) decrease in the LPP modulation; in participants with higher trait anxiety, propranolol increased the emotion-related LPP modulation.
CONCLUSIONS
These results provide initial support for the hypothesis that the LPP reflects the downstream effects, in visual cortical areas, of β-receptor-mediated activation of the amygdala.Stress-related psychiatric disorders across the life spa
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Catecholamine-mediated increases in neural gain improve the precision of cortical representations
Neurophysiological evidence suggests that neuromodulators, such as norepinephrine and dopamine, increase neural gain in target brain areas. Computational models and prominent theoretical frameworks indicate that this should enhance the precision of neural representations, but direct empirical evidence for this hypothesis is lacking. In two functional MRI studies, we examine the effect of baseline catecholamine levels (as indexed by pupil diameter and manipulated pharmacologically) on the precision of object representations in the human ventral temporal cortex using angular dispersion, a powerful, multivariate metric of representational similarity (precision). We first report the results of computational model simulations indicating that increasing catecholaminergic gain should reduce the angular dispersion, and thus increase the precision, of object representations from the same category, as well as reduce the angular dispersion of object representations from distinct categories when distinct-category representations overlap. In Study 1 (N = 24), we show that angular dispersion covaries with pupil diameter, an index of baseline catecholamine levels. In Study 2 (N = 24), we manipulate catecholamine levels and neural gain using the norepinephrine transporter blocker atomoxetine and demonstrate consistent, causal effects on angular dispersion and brain-wide functional connectivity. Despite the use of very different methods of examining the effect of baseline catecholamine levels, our results show a striking convergence and demonstrate that catecholamines increase the precision of neural representations
Catecholaminergic neuromodulation shapes intrinsic MRI functional connectivity in the human brain
The brain commonly exhibits spontaneous (i.e., in the absence of a task) fluctuations in neural activity that are correlated across brain regions. It has been established that the spatial structure, or topography, of these intrinsic correlations is in part determined by the fixed anatomical connectivity between regions. However, it remains unclear which factors dynamically sculpt this topography as a function of brain state. Potential candidate factors are subcortical catecholaminergic neuromodulatory systems, such as the locus ceruleus-norepinephrine system, which send diffuse projections to most parts of the forebrain. Here, we systematically characterized the effects of endogenous central neuromodulation on correlated fluctuations during rest in the human brain. Using a double-blind placebo-controlled crossover design, we pharmacologically increased synaptic catecholamine levels by administering atomoxetine, an NE transporter blocker, and examined the effects on the strength and spatial structure of resting-state MRI functional connectivity. First, atomoxetine reduced the strength of inter-regional correlations across three levels of spatial organization, indicating that catecholamines reduce the strength of functional interactions during rest. Second, this modulatory effect on intrinsic correlations exhibited a substantial degree of spatial specificity: the decrease in functional connectivity showed an anterior-posterior gradient in the cortex, depended on the strength of baseline functional connectivity, and was strongest for connections between regions belonging to distinct resting-state networks. Thus, catecholamines reduce intrinsic correlations in a spatially heterogeneous fashion. We conclude that neuromodulation is an important factor shaping the topography of intrinsic functional connectivity
Beta receptor-mediated modulation of the oddball P3 but not error-related ERP components in humans
Sociodemographic and substance use characteristics of Îł hydroxybutyrate (GHB) dependent inpatients and associations with dependence severity
The number of admissions to addiction treatment centers in the Netherlands for gamma hydroxybutyrate (GHB) dependence is rapidly growing. Until now, treatment seeking GHB users have hardly been studied. This study characterizes inpatients in treatment for GHB dependence in terms of sociodemographics, motives for substance use and reasons for seeking treatment. In addition, variables associated with dependence severity are identified. Patients were recruited by their therapists at 4 different addiction treatment centers dispersed throughout the Netherlands. They were asked to fill out the questionnaire, including sociodemographic and clinical characteristics, GHB and other drug use, and a modified version of the Drug Use Disorders Identification Test (DUDIT) to screen for GHB dependence. The associations of relevant variables with dependence severity were determined using multiple regression analysis. A total of 75 inpatients (response rate 90.4%) participated in the study. Most patients were young (mean 26.8 ± 9.1) males (73%) with low education (78%) and not employed (48%). Most of them (75%) had started using GHB the year before treatment admission, 42 (56%) frequently combined GHB with sedatives and 26 (35%) frequently combined GHB with stimulants. Dependence severity was strongly associated with sleep problems and the combined use of GHB and stimulants. This study shows that sociodemographic characteristics of GHB inpatients are similar to those of problematic users of other club drugs. Sleep problems and combined use of GHB and stimulants were strongly associated with GHB dependence. Together, these factors might help to better identify people at risk for GHB dependenc
A Case Series of Pharmaceutical Gamma-Hydroxybutyrate in 3 Patients With Severe Benzodiazepine-Resistant Gamma-Hydroxybutyrate Withdrawal in the Hospital
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The effect of atomoxetine on random and directed exploration in humans
The adaptive regulation of the trade-off between pursuing a known reward ( exploitation) and sampling lesser-known options in search of something better ( exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system. We administered atomoxetine, a norepinephrine transporter blocker that increases extracellular levels of norepinephrine throughout the cortex, to 22 healthy human participants in a double-blind crossover design. We examined the effect of treatment on performance in a gambling task designed to produce distinct measures of directed exploration and random exploration. In line with our hypothesis we found an effect of atomoxetine on random, but not directed exploration. However, contrary to expectation, atomoxetine reduced rather than increased random exploration. We offer three potential explanations of our findings, involving the non-linear relationship between tonic NE and cognitive performance, the interaction of atomoxetine with other neuromodulators, and the possibility that atomoxetine affected phasic norepinephrine activity more so than tonic norepinephrine activity.European Research Council [StG_2011 283314]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Data from: The effect of atomoxetine on random and directed exploration in humans
The adaptive regulation of the trade-off between pursuing a known reward (exploitation) and sampling lesser-known options in search of something better (exploration) is critical for optimal performance. Theory and recent empirical work suggest that humans use at least two strategies for solving this dilemma: a directed strategy in which choices are explicitly biased toward information seeking, and a random strategy in which decision noise leads to exploration by chance. Here we examined the hypothesis that random exploration is governed by the neuromodulatory locus coeruleus-norepinephrine system. We administered atomoxetine, a norepinephrine transporter blocker that increases extracellular levels of norepinephrine throughout the cortex, to 22 healthy human participants in a double-blind crossover design. We examined the effect of treatment on performance in a gambling task designed to produce distinct measures of directed exploration and random exploration. In line with our hypothesis we found an effect of atomoxetine on random, but not directed exploration. However, contrary to expectation, atomoxetine reduced rather than increased random exploration. We speculate that our results may be due to interactions with other neuromodulators that are also affected by atomoxetine, or that the reduction in random exploration was driven by a drug-related increase in phasic norepinephrine activity rather than in baseline norepinephrine levels