Serotonergic Modulation of Cognition, Emotion and Brain Activation in Healthy Volunteers
Study Details
Study Description
Brief Summary
The aim of this project is:
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To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
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To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
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To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
The aim of this project is:
-
To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
-
To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
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To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.
Serotonin is a monoamine neurotransmitter implicated in diverse cognitive and affective brain functions. Serotonin has a significant role in the regulation of cognition and mood, including emotional appraisal, perception and flexible behaviour, with 5-HT receptors found in the cortex, amygdala and hippocampus. The investigators have previously shown that in healthy human experimental studies, acute dietary tryptophan depletion induces 'waiting' impulsivity and impulsive behaviours, impairs goal-directed behaviour and shifts behavioural control toward habitual responding when appetitive, but goal-directed when aversive. Reduced availability of forebrain serotonin has also shown to impair a range of cognitive processes, such as psychomotor processing, episodic memory, attention and executive function. Recently, the research team have shown that using an acute and clinically relevant dose (20 mg) of escitalopram impaired learning and cognitive flexibility, but improved response inhibition in healthy humans, suggesting a dissociation of effects possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits.
The investigators now aim to investigate the effects of sub-chronic administration of 20 mg of escitalopram (i.e. three weeks) in healthy volunteers using sophisticated neuropsychological testing (Cambridge Neuropsychological Test Automated Battery and EMOTICOM) and functional magnetic resonance imaging (fMRI). Whereas 'cold' cognition refers to the use of non-emotional processing (e.g. episodic memory; spatial working memory), 'hot' cognition is emotion-laden and used in response to stimuli with affective salience (e.g. decision-making under high levels of risk of uncertainty). It has been suggested that cognitive-emotional effects, such as the re-appraisal and re-evaluation of emotions underlying learning mechanisms, may mediate improvements in mood associated with SSRI treatment. This project will help further the understanding of the role of serotonin in the regulation of cognitive and emotional processes, as well the neural correlates underlying reinforcement learning, in healthy humans.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Control Group The placebo control group will be administered the exact same procedure as the intervention group, the only difference being that this group will be administered a placebo pill. |
Drug: Placebo
Placebo daily for approximately 3 weeks.
|
| Experimental: Intervention Group The intervention group will be administered 20mg of Escitalopram daily for approximately 3 weeks. |
Drug: Escitalopram 20 mg
20mg daily for approximately 3 weeks.
|
Outcome Measures
Primary Outcome Measures
- Learning Primary Outcome 1: Mean errors Stage 1 (Learning) - Probability Reversal Learning. [3 years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Learning Primary Outcome 2: Mean errors Stage 2 (Reversal) - Probability Reversal Learning. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Learning Primary Outcome 3: Learning Rate in Reward Trial - Reinforcement Learning. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Learning Primary Outcome 4: Learning Rate in Punishment Trials - Reinforcement Learning. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Inhibition Primary Outcome 1: Stop Signal Reaction Time - Interleaved Stop Signal Task/Go-NoGo. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Executive Function Primary Outcome 1: Extra Dimensional Set Errors -3Dimensional Intra/Extra Dimensional Shift. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Reinforcement Behaviour Model [3 Years]
A model comparison will be conducted to determine the winning model of reinforcement behaviour using one, a combination of, or all these parameters. The winning model will be a single outcome model. Reward Learning Rate Punishment Learning Rate Reinforcement Sensitivity Stimulus Stickiness
- Social Cognition Primary Outcome 1: Proportion of offers accepted - Ultimatum Game [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Social Cognition Primary Outcome 2: Agent Guilt Score - Moral Emotions Task. [3 Years]
3. Agent Shame Score ---------- Moral Emotions Task Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Social Cognition Primary Outcome 3: Agent Shame Score - Moral Emotions Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Primary Outcome 1: Affective bias in decreasing condition - EMOTICOM Intensity Morphing. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Primary Outcome 2: Affective bias for D' - EMOTICOM Emotion Recognition Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Primary Outcome 3: Detection threshold decreasing - EMOTICOM Intensity Morphing. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Primary Outcome 4: D'Prime for Emotion Recognition - EMOTICOM Emotion Recognition Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Biofluids: Serum Escitalopram levels [3 Years]
- PET Imaging: Cerebral (particularly hippocampal) presynaptic density, as measured with 11 C-UCB-J-PET. [3 Years]
Collected in a sub-sample of participants.
Secondary Outcome Measures
- Learning Secondary Outcome 1: Stage 1 Reward-Stay/Lose-Shift behaviour - Probability Reversal Learning. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Learning Secondary Outcome 2: Stage 2 Reward-Stay/ Lose-Shift behaviour - Probability Reversal Learning. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Learning Secondary Outcome 3: Pre Extra Dimension Set Errors - 3Dimensional Intra/Extra Dimensional Shift. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Learning Secondary Outcome 4: Proportion of Stays - Sequential Model-Based/Model-Free. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Inhibition Secondary Outcome 1: Go reaction time - Interleaved Stop Signal Task/Go-NoGo. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Inhibition Secondary Outcome 2: Go omission error rate - Interleaved Stop Signal Task/Go-NoGo. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Inhibition Secondary Outcome 3: Go commission error rate - Interleaved Stop Signal Task/Go-NoGo. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Inhibition Secondary Outcome 4: No-Go error rate - Interleaved Stop Signal Task/Go-NoGo. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Executive Function Secondary Outcome 1: Total Errors Adjusted - 3Dimensional Intra/Extra Dimensional Shift. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Executive Function Secondary Outcome 2: Strategy Score - CANTAB Spatial Working Memory. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Social Cognition Secondary Outcome 1: Fairness Sensitivity---------- Ultimatum Game [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Secondary Outcome 1: Detection threshold increasing - EMOTICOM Intensity Morphing. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Secondary Outcome 2: Affective bias in increasing condition - EMOTICOM Intensity Morphing. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Secondary Outcome 3: Affective bias for Hit Rate - EMOTICOM Emotion Recognition Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Emotion Recognition Secondary Outcome 4: Hit Rate for Emotion Recognition - EMOTICOM Emotion Recognition Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Faces and geometric figure discrimination Outcome 1: Accuracy - Faces fMRI paradigm [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Faces and geometric figure discrimination Outcome 2: Response Speed - Faces fMRI paradigm. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Memory Outcome 1: Total Errors Adj - CANTAB Paired Associates Learning [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Memory Outcome 2: First Trial Memory Score - CANTAB Paired Associates Learning. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Memory Outcome 3: Between Search Errors - CANTAB Spatial Working Memory. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Attention Outcome 1: Target Sensitivity (A') - CANTAB Rapid Visual Processing. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Attention Outcome 2: Latency - CANTAB Rapid Visual Processing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Attention Outcome 3: Probability of False Alarms - CANTAB Rapid Visual Processing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Risky Decision Making Outcome Outcome 1. Quality of Decision Making - EMOTICOM Cambridge Gamble Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Risky Decision Making Outcome 2: Risk Adjustment - EMOTICOM Cambridge Gamble Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Risky Decision Making Outcome 3: Overall Proportion Bet - EMOTICOM Cambridge Gamble Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Risky Decision Making Outcome 4: Deliberation Time - EMOTICOM Cambridge Gamble Task. [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Psychomotor Speed Outcome 1: Simple reaction time - CANTAB Reaction Time Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Psychomotor Speed Outcome 2: Five Choice reaction time - CANTAB Reaction Time Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
- Neural Activations and Correlations - Reinforcement Learning fMRI paradigm [3 Years]
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
- Neural Activations and Correlations - Faces fMRI paradigm [3 Years]
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
- Resting State fMRI [3 Years]
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
- Structural VBM [3 Years]
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
- Diffusion Tensor Imaging [3 Years]
- Profile of Mood State Score [3 Years]
- Beck Depression Inventory-II Score [3 Years]
- State-Trait Anxiety Inventory Scale -State Score [3 Years]
- State and Trait Aggression Questionnaire-State Score [3 Years]
- Baret Impulsivity Scale-State Score [3 Years]
- Visual Analogue Scale Score [3 Years]
- Interpersonal Reactivity Index Score [3 Years]
- Obsessive- Compulsive Inventory Score [3 Years]
- Brief Symptom Checklist Score [3 Years]
- Pittsburgh Sleep Quality Index Score [3 Years]
Other Outcome Measures
- Emotion Recognition Other Outcome 1: Detection threshold decreasing Happy - Intensity Morphing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 2: Detection threshold decreasing Sad - Intensity Morphing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 3: Detection threshold decreasing Anger - Intensity Morphing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 4: Detection threshold decreasing Fear - Intensity Morphing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 5: Detection threshold decreasing Disgust - Intensity Morphing [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 6: D' Happy - Emotion Recognition Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 7: D' Sad - Emotion Recognition Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 8: D' Fear - Emotion Recognition Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Emotion Recognition Other Outcome 9: D' Anger - Emotion Recognition Task [3 Years]
Outcome variables have been grouped a priori into carefully defined cognitive domains.
- Activity Level Score [3 Years]
- Behavioural Inhibition/ Behavioural Avoidance Scale Score [3 Years]
- The Compulsive Personality Assessment Scale Score [3 Years]
- Sexuality Questionnaire Score [3 Years]
- Edinburgh Handedness Inventory Score [3 Years]
- Revised NEO Personality Questionnaire Score [3 Years]
- Family History Assessment Module Score [3 Years]
- Positive Life Events Score [3 Years]
- Stressful Life Events Score [3 Years]
- State and Trait Aggression Questionnaire -Trait Score [3 Years]
- Barret Impulsivity Scale-Trait Score [3 Years]
- The Penn State Worry Questionnaire- Trait Score [3 Years]
- The Penn State Worry Questionnaire- State Score [3 Years]
- The Self-Control Scale- Trait Score [3 Years]
- The Self-Control Scale- State Score [3 Years]
- State- Trait Anxiety Inventory- Trait Score [3 Years]
- The Warwick-Edinburgh Mental Well-being Scale -Trait Score [3 Years]
- The Warwick-Edinburgh Mental Well-being Scale -State Score [3 Years]
- Mindful Attention and Awareness Scale -Trait Score [3 Years]
- Mindful Attention and Awareness Scale -State Score [3 Years]
- The Intolerance of Uncertainty Scale - Trait Score [3 Years]
- The Intolerance of Uncertainty Scale - State Score [3 Years]
- Verran Snyder-Halpern (VSH) Sleep Scale Score [3 Years]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Healthy volunteer (male or female) between 18 and 45 years.
Exclusion Criteria:
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Current or former primary psychiatric disorder (DSM IV Axis I or WHO ICD-10 diagnostic classification).
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Current or previous neurological disease, severe somatic disease, or the consumption of drugs likely to influence the test results.
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Non- fluent in Danish or pronounced visual or auditory impairments.
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Current or past learning disability.
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Pregnancy (females).
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Lactation (females).
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Contraindications for MRI (pacemaker, metal implants, etc.).
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Allergy to the ingredients in the administered drug.
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Abnormal ECG (e.g. prolonged QT syndrome).
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Dizzy when changing from supine to upright position (e.g. postural orthostatic tachycardia syndrome).
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Mild hypotension (blood pressure below 100/70 mmHg) or hypertension (blood pressure above 140/90 mmHg).
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Head injury or concussion resulting in loss of consciousness for more than 2 min.
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Alcohol or drug abuse.
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Drug use other than tobacco and alcohol within the last 30 days.
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Hash > 50 x lifetime.
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Drugs > 10 x lifetime (for each substance).
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Nicotine addiction.
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Current psychoactive medication.
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Severe physical impairments affecting eyesight or motor performance.
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Hamilton-6 depression scale score > 5.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Neurobiology Research Unit | Copenhagen | Denmark | DK-2100 |
Sponsors and Collaborators
- Rigshospitalet, Denmark
- University of Cambridge
- Lundbeck Foundation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Bland AR, Roiser JP, Mehta MA, Schei T, Boland H, Campbell-Meiklejohn DK, Emsley RA, Munafo MR, Penton-Voak IS, Seara-Cardoso A, Viding E, Voon V, Sahakian BJ, Robbins TW, Elliott R. EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition. Front Behav Neurosci. 2016 Feb 24;10:25. doi: 10.3389/fnbeh.2016.00025. eCollection 2016.
- Homberg JR. Serotonin and decision making processes. Neurosci Biobehav Rev. 2012 Jan;36(1):218-36. doi: 10.1016/j.neubiorev.2011.06.001. Epub 2011 Jun 12. Review.
- Meneses A. Are 5-HT(1B/1D) and 5-HT(2A/2B/2C) receptors involved in learning and memory processes? IDrugs. 1999 Aug;2(8):796-801.
- Park SB, Coull JT, McShane RH, Young AH, Sahakian BJ, Robbins TW, Cowen PJ. Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology. 1994 Mar-Apr;33(3-4):575-88.
- Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain. 1988 Jun;111 ( Pt 3):695-718.
- Worbe Y, Palminteri S, Savulich G, Daw ND, Fernandez-Egea E, Robbins TW, Voon V. Valence-dependent influence of serotonin depletion on model-based choice strategy. Mol Psychiatry. 2016 May;21(5):624-9. doi: 10.1038/mp.2015.46. Epub 2015 Apr 14.
- Worbe Y, Savulich G, de Wit S, Fernandez-Egea E, Robbins TW. Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans. Int J Neuropsychopharmacol. 2015 Feb 5;18(10):pyv013. doi: 10.1093/ijnp/pyv013.
- Worbe Y, Savulich G, Voon V, Fernandez-Egea E, Robbins TW. Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance. Neuropsychopharmacology. 2014 May;39(6):1519-26. doi: 10.1038/npp.2013.351. Epub 2014 Jan 2.
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