Pharmacological fMRI Study Research Articles

Resting-state functional MRI as a tool for evaluating brain hemodynamic responsiveness to external stimuli in rats.

Anesthesia is a major confounding factor in functional MRI (fMRI) experiments attributed to its effects on brain function. Recent evidence suggests that parameters obtained with resting-state fMRI (rs-fMRI) are coupled with anesthetic depth. Therefore, we investigated whether parameters obtained with rs-fMRI, such as functional connectivity (FC), are also directly related to blood-oxygen-level-dependent (BOLD) responses. A simple rs-fMRI protocol was implemented in a pharmacological fMRI study to evaluate the coupling between hemodynamic responses and FC under five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane). Temporal change in the FC was evaluated at 1-hour interval. Supplementary forepaw stimulation experiments were also conducted. Under thiobutabarbital anesthesia, FC was clearly coupled with nicotine-induced BOLD responses. Good correlation values were also obtained under isoflurane and medetomidine anesthesia. The observations in the thiobutabarbital group were supported by forepaw stimulation experiments. Additionally, the rs-fMRI protocol revealed significant temporal changes in the FC in the α-chloralose, thiobutabarbital, and urethane groups. Our results suggest that FC can be used to estimate brain hemodynamic responsiveness to stimuli and evaluate the level and temporal changes of anesthesia. Therefore, analysis of the fMRI baseline signal may be highly valuable tool for controlling the outcome of preclinical fMRI experiments. Magn Reson Med 78:1136-1146, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study.

Sex-hormone fluctuations may increase risk for developing depressive symptoms and alter emotional processing as supported by observations in menopausal and pre- to postpartum transition. In this double-blinded, placebo-controlled study, we used blood−oxygen level dependent functional magnetic resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16±3 days post intervention. At both sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol to menopausal levels, which was accompanied by an increase in subclinical depressive symptoms relative to placebo. Women who displayed larger GnRHa-induced increase in depressive symptoms had a larger increase in both negative and positive emotion-elicited activity in the anterior insula. When considering the post-GnRHa scan only, depressive responses were associated with emotion-elicited activity in the anterior insula and amygdala. The effect on regional activity in anterior insula was not associated with the estradiol net decline, only by the GnRHa-induced changes in mood. Our data implicate enhanced insula recruitment during emotional processing in the emergence of depressive symptoms following sex-hormone fluctuations. This may correspond to the emotional hypersensitivity frequently experienced by women postpartum.

Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study

The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model – a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans.

Brain Functional Effects of Psychopharmacological Treatment in Major Depression: a Focus on Neural Circuitry of Affective Processing.

In the last two decades, neuroimaging research has reached a much deeper understanding of the neurobiological underpinnings of major depression (MD) and has converged on functional alterations in limbic and prefrontal neural networks, which are mainly linked to altered emotional processing observed in MD patients. To date, a considerable number of studies have sought to investigate how these neural networks change with pharmacological antidepressant treatment. In the current review, we therefore discuss results from a) pharmacological functional magnetic resonance imaging (fMRI) studies investigating the effects of selective serotonin or noradrenalin reuptake inhibitors on neural activation patterns in relation to emotional processing in healthy individuals, b) treatment studies in patients with unipolar depression assessing changes in neural activation patterns before and after antidepressant pharmacotherapy, and c) predictive neural biomarkers of clinical response in depression. Comparing results from pharmacological fMRI studies in healthy individuals and treatment studies in depressed patients nicely showed parallel findings, mainly for a reduction of limbic activation in response to negative stimuli. A thorough investigation of the empirical findings highlights the importance of the specific paradigm employed in every study which may account for some of the discrepant findings reported in treatment studies in depressed patients.

Dopamine and memory dedifferentiation in aging

The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (1.25mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between aging, dopaminergic function and dedifferentiation in the hippocampus.

Butorphanol Suppression of Histamine Itch Is Mediated by Nucleus Accumbens and Septal Nuclei: A Pharmacological fMRI Study

Opioid receptors in the central nervous system are important modulators of itch transmission. In this study, we examined the effect of mixed-action opioid butorphanol on histamine itch, cowhage itch and heat pain in healthy volunteers. Using functional MRI, we investigated significant changes in cerebral perfusion to identify the critical brain centers mediating the antipruritic effect of butorphanol. Butorphanol suppressed the itch induced experimentally with histamine, reduced the intensity of cowhage itch by approximately 35%, and did not affect heat pain sensitivity. In comparison with the placebo, butorphanol produced a bilateral deactivation of claustrum, insula and putamen, areas activated during itch processing. Analysis of cerebral perfusion patterns of brain processing of itch vs. itch inhibition under the effect of the drug, revealed that the reduction of cowhage itch by butorphanol was correlated with changes in cerebral perfusion in the midbrain, thalamus, S1, insula and cerebellum. The suppression of histamine itch by butorphanol was paralleled by the activation of nucleus accumbens and septal nuclei, structures expressing high levels of kappa opioid receptors. In conclusion, important relays of the mesolimbic circuit were involved in the inhibition of itch by butorphanol and could represent potential targets for the development of antipruritic therapy.

The Effects of Drug Induced Changes in Dopamine and Galantamine Levels on Attentional Selection and Working Memory Storage in Young and Elderly. A Pharmacological fMRI Study.

Event Abstract Back to Event The Effects of Drug Induced Changes in Dopamine and Galantamine Levels on Attentional Selection and Working Memory Storage in Young and Elderly. A Pharmacological fMRI Study. Anne Vellage1, 2*, Andreas Becke3, Hendrik Strumpf4, Max Hopf5, Ariel Schönfeld5 and Notger Müller1 1 German Centre of Neurodegenerative Diseases, Germany 2 Berlin School of Mind and Brain, Germany 3 Institute for Cognitive Neurology and Dementia Research, Germany 4 Leibniz Intsitute for Neurobiology, Germany 5 Leibniz Institute for Neurobiology, Germany Attentional selection and storage of relevant information in working memory (WM) are influenced by different neurotransmitters. A key role in memory processes plays dopamine (DA) which seems to modulate WM via dopaminergic neurons mainly in prefrontal cortex and basal ganglia. Former Studies have shown that basal ganglia are involved in controlling access of information to WM. Attentional filtering processes seem to be supported by acetylcholine (Ach). Cholinergic receptors in the parietal cortex that are innervated by the upcoming cholinergic system from the basal forebrain might explain this relation. During normal aging neuronal structures degenerate, leading to a decreasing level of neurotransmitter in the brain and deficits in certain cognitive abilities. In this study we investigated the effects of pharmacological modulation of neurotransmitter levels on memory and attention processes in young (20-30 ys.) and old (60-75 ys.) healthy subjects via fMRI (3T). In two sessions each of the subjects received either a placebo or a drug (Levodopa 100 mg + 25 mg Carbidopa/ Galantamine 8 mg) and performed a delayed-match-to-sample task with high and low demands on filtering and memory processes. We found an extensive neuronal network during filtering in both age groups, including occipital cortex, the thalamus, basal ganglia and various regions in the prefrontal cortex. Confirming the results of former studies we found the right parietal cortex to be activated during memory processes. Increasing the DA and Ach levels via drug had strong effects on these regions which differed between age groups. These findings show that brain areas related to storage or attention are differentially recruited during age, depending on the baseline neurotransmitter level. Pharmacological modulation of DA and Ach level can lead to a more effective recruitment of these brain areas in elderly people and an improvement in cognitive abilities like WM and selective attention. Keywords: Acetylcholine, Dopamine, fMRI, working memory, selective attention Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Memory and Learning Citation: Vellage A, Becke A, Strumpf H, Hopf M, Schönfeld A and Müller N (2015). The Effects of Drug Induced Changes in Dopamine and Galantamine Levels on Attentional Selection and Working Memory Storage in Young and Elderly. A Pharmacological fMRI Study.. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00352 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Mrs. Anne Vellage, German Centre of Neurodegenerative Diseases, Magdeburg, Germany, a.vellage@googlemail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anne Vellage Andreas Becke Hendrik Strumpf Max Hopf Ariel Schönfeld Notger Müller Google Anne Vellage Andreas Becke Hendrik Strumpf Max Hopf Ariel Schönfeld Notger Müller Google Scholar Anne Vellage Andreas Becke Hendrik Strumpf Max Hopf Ariel Schönfeld Notger Müller PubMed Anne Vellage Andreas Becke Hendrik Strumpf Max Hopf Ariel Schönfeld Notger Müller Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Brain biomarkers of treatment for multi-domain dysfunction: pharmacological FMRI studies in pediatric mania.

It is well established that pediatric bipolar disorder (PBD) not only presents with affected dysregulation but also cognitive difficulties in working memory, attention, verbal memory, and executive functional domains (Pavuluri et al, 2009). Neural circuitry abnormalities that explain this multi-domain dysfunction (Pavuluri, in press) have led to the pursuit of how such abnormal pathophysiology can be reversed with pharmacotherapy (Mayanil et al, 2011). We conducted the first series of fMRI studies in pediatric mania by examining the effects of lamotrigine, risperidone, and divalproex sodium (DVPX) individually as well as through a pharmacotherapy algorithm. The pharmacological fMRI studies used tasks to probe the domains of emotion processing, response inhibition, and the interface of emotion and cognition. Biomarkers of pharmacotherapy response, especially the increase in ventrolateral prefrontal cortex (VLPFC) activity in PBD relative to the healthy controls (HC), have been tied to the reduction in manic symptoms regardless of any task (Mayanil et al, 2011). Most studies summarized here were conducted on adolescents suffering from hypomanic state at baseline and are illustrated in Figure 1.

P.1.g.005 Serotonergic modulation of emotion processing by the mixed 5-HT1A/2A receptor agonist psilocybin reduces amygdala activation to negative stimuli – a pharmacological fMRI study

P.1.g.005 Serotonergic modulation of emotion processing by the mixed 5-HT1A/2A receptor agonist psilocybin reduces amygdala activation to negative stimuli – a pharmacological fMRI study

Dose-dependent effects of intravenous alcohol administration on cerebral blood flow in young adults.

Functional magnetic resonance imaging (fMRI) studies involving alcohol challenge are important for identifying neural correlates of alcohol's psychopharmacological effects. However, evaluating acute alcohol effects on blood oxygen level-dependent (BOLD) signal change is complicated by alcohol-related increases in cerebral blood flow (CBF). The present study aimed to further characterize acute alcohol effects on CBF using intravenous alcohol administration to maximize control over brain alcohol exposure. Twenty heavy-drinking young adults (M = 19.95 years old, SD = 0.76) completed alcohol and placebo imaging sessions in a within-subject, counter-balanced, placebo-controlled design. Arterial spin labeling (ASL) provided estimates of perfusion change at two target blood alcohol concentrations (40 and 80 mg%) relative to baseline and relative to a saline control infusion. Voxel-wise analyses showed widespread and dose-dependent effects of alcohol on CBF increase. Region-of-interest analyses confirmed these findings, also indicating regional variation in the magnitude of perfusion change. Additional findings indicated that lower self-reported sensitivity to alcohol corresponded with reduced perfusion change during alcohol administration. This study provides further evidence for widespread effects of acute alcohol on cerebral perfusion, also demonstrating regional, dose-dependent, and inter-individual variation. Further research is needed to evaluate implications of these effects for the design and interpretation of pharmacological fMRI studies involving alcohol challenge.

The endocannabinoid system and emotional processing: A pharmacological fMRI study with ∆9-tetrahydrocannabinol

Various psychiatric disorders such as major depression are associated with abnormalities in emotional processing. Evidence indicating involvement of the endocannabinoid system in emotional processing, and thus potentially in related abnormalities, is increasing. In the present study, we examined the role of the endocannabinoid system in processing of stimuli with a positive and negative emotional content in healthy volunteers. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist ∆9-tetrahydrocannabinol (THC) on brain function related to emotional processing in 11 healthy subjects. Performance and brain activity during matching of stimuli with a negative (‘fearful faces’) or a positive content (‘happy faces’) were assessed after placebo and THC administration. After THC administration, performance accuracy was decreased for stimuli with a negative but not for stimuli with a positive emotional content. Our task activated a network of brain regions including amygdala, orbital frontal gyrus, hippocampus, parietal gyrus, prefrontal cortex, and regions in the occipital cortex. THC interacted with emotional content, as activity in this network was reduced for negative content, while activity for positive content was increased. These results indicate that THC administration reduces the negative bias in emotional processing. This adds human evidence to support the hypothesis that the endocannabinoid system is involved in modulation of emotional processing. Our findings also suggest a possible role for the endocannabinoid system in abnormal emotional processing, and may thus be relevant for psychiatric disorders such as major depression.

The role of dopamine in inhibitory control in smokers and non-smokers: A pharmacological fMRI study

Contemporary theoretical models of substance dependence posit that deficits in inhibitory control play an important role in substance dependence. The neural network underlying inhibitory control and its association with substance dependence have been widely investigated. However, the pharmacology of inhibitory control is still insufficiently clear. The aims of the current study were twofold. First, we investigated the role of dopamine in inhibitory control and associated brain activation. Second, the proposed link between dopamine and impaired inhibitory control in nicotine dependence was investigated by comparing smokers and non-smoking controls. Haloperidol (2mg), a dopamine D2/D3 receptor antagonist, and placebo were administered to 25 smokers and 25 non-smoking controls in a double-blind randomized cross-over design while performing a Go/NoGo task during fMRI scanning. Haloperidol reduced NoGo accuracy and associated brain activation in the ACC, right SFG and left IFG, showing that optimal dopamine levels are crucial to effectively implement inhibitory control. In addition, smokers showed behavioral deficits on the Go/NoGo task as well as hypoactivity in the left IFG, right MFG and ACC after placebo, supporting the hypothesis of a hypoactive prefrontal system in smokers. Haloperidol had a stronger impact on prefrontal brain activation in non-smoking controls compared to smokers, which is in line with the inverted ‘U’ curve theory of dopamine and cognitive control. The current findings suggest that altered baseline dopamine levels in addicted individuals may contribute to the often observed reduction in inhibitory control in these populations.

Dopaminergic dysfunction in abstinent dexamphetamine users: Results from a pharmacological fMRI study using a reward anticipation task and a methylphenidate challenge

BackgroundDopamine (DA) is involved in systems governing motor actions, motivational processes and cognitive functions. Preclinical studies have shown that even relatively low doses of d-amphetamine (dAMPH) (equivalent to doses used in clinical Practice) can lead to DA neurotoxicity in rodents and non-human primates (Ricaurte et al., 2005). MethodsTherefore, we investigated the DAergic function in eight male recreational users of dAMPH and eight male healthy controls using functional magnetic resonance imaging (fMRI). We compared brain activation between both groups during a monetary incentive delay task (Knutson et al., 2001) with and without an oral methylphenidate (MPH) challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1.5h after receiving an oral dose of 35mg MPH (approximately 0.5mg/kg) when peak MPH binding was assumed. ResultsWhen anticipating reward, dAMPH users showed lower striatal activation in comparison to control subjects. In addition, MPH induced a reduction in the striatal activation during reward anticipation in healthy controls, whereas no such effect was observed in dAMPH users. ConculsionThe combination of these findings provides further evidence for frontostriatal DAergic dysfunction in recreational dAMPH users and is consistent with preclinical data suggesting neurotoxic effects of chronic dAMPH use. The findings of this explorative study could have important implications for humans in need for treatment with dAMPH, such as patients suffering from ADHD and therefore this study needs replication in a larger sample.

Effects of Δ9-Tetrahydrocannabinol Administration on Human Encoding and Recall Memory Function: A Pharmacological fMRI Study

Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Δ9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans.

Modulatory Effects of Levodopa on Cognitive Control in Young but not in Older Subjects: A Pharmacological fMRI Study

Older individuals show decline of prefrontal cortex (PFC) functions which may be related to altered dopaminergic neurotransmission. We investigated the effects of aging and dopaminergic stimulation in 15 young and 13 older healthy subjects on the neural correlates of interference control using fMRI. In a double-blind, placebo-controlled within-subject design, subjects were measured after levodopa (100 mg) or placebo administration. In each session, subjects performed a visual-spatial interference task based on a Stroop/Simon-like paradigm. Across age groups, interference (incongruent relative to congruent trials) was associated with activations in the presupplementary motor area, ACC, and intraparietal cortex. Increased interference was found behaviorally in older volunteers. Differential activation in left dorsolateral PFC in young subjects and bilateral PFC activity in older subjects was observed to be associated with interference control. Performance deteriorated under levodopa only in young subjects. This was accompanied by an increase of neural activity in ACC (p < .05; small-volume correction for multiple comparisons). Worsening of performance under levodopa in young subjects and the associated effect on ACC may indicate that overstimulation of the dopaminergic system compromises interference control. This supports the inverted-U-shaped model of neurotransmitter action.

Effects of caffeine on attentional networks in healthy individuals: A pharmacological fMRI study

Effects of caffeine on attentional networks in healthy individuals: A pharmacological fMRI study

P.1.e.006 Involvement of the endocannabinoid system in executive function: a pharmacological fMRI study with delta9-tetrahydrocannabinol (THC)

P.1.e.006 Involvement of the endocannabinoid system in executive function: a pharmacological fMRI study with delta9-tetrahydrocannabinol (THC)

P.1.e.007 The effects of delta9-tetrahydrocannabinol (THC) on human brain function involved in emotional processing: a pharmacological fMRI study

P.1.e.007 The effects of delta9-tetrahydrocannabinol (THC) on human brain function involved in emotional processing: a pharmacological fMRI study

Involvement of the endocannabinoid system in reward processing in the human brain.

RationaleDisturbed reward processing in humans has been associated with a number of disorders, such as depression, addiction, and attention-deficit hyperactivity disorder. The endocannabinoid (eCB) system has been implicated in reward processing in animals, but in humans, the relation between eCB functioning and reward is less clear.ObjectivesThe current study uses functional magnetic resonance imaging (fMRI) to investigate the role of the eCB system in reward processing in humans by examining the effect of the eCB agonist Δ9-tetrahydrocannabinol (THC) on reward-related brain activity.MethodsEleven healthy males participated in a randomized placebo-controlled pharmacological fMRI study with administration of THC to challenge the eCB system. We compared anticipatory and feedback-related brain activity after placebo and THC, using a monetary incentive delay task. In this task, subjects are notified before each trial whether a correct response is rewarded (“reward trial”) or not (“neutral trial”).ResultsSubjects showed faster reaction times during reward trials compared to neutral trials, and this effect was not altered by THC. THC induced a widespread attenuation of the brain response to feedback in reward trials but not in neutral trials. Anticipatory brain activity was not affected.ConclusionsThese results suggest a role for the eCB system in the appreciation of rewards. The involvement of the eCB system in feedback processing may be relevant for disorders in which appreciation of natural rewards may be affected such as addiction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2428-8) contains supplementary material, which is available to authorized users.

Cholinergic enhancement augments the magnitude and specificity of perceptual learning in the human visual system: a pharmacological fMRI study

Cholinergic enhancement augments the magnitude and specificity of perceptual learning in the human visual system: a pharmacological fMRI study