Effects of Ketamine on Eye Movements, Perception and Brain Function

Study Overview
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Brief Summary
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In this study, the investigators examine the effects of low-dose ketamine on different oculomotor, perceptual and cognitive functions. They also examine effects on concurrent brain activity using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). A sample of N=25 healthy, male participants is required to complete the study. The design is within-subjects, placebo-controlled, double-blind and cross-over. A targeted ketamine level in plasma of 100ng/ml is applied. It is hypothesised that ketamine, compared to placebo, will lead to changes in task performance and brain activity similar to those observed in patients with schizophrenia.

Detailed Description
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The uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been proposed as a model system of the symptoms of schizophrenia. To complement this model system and to allow neurobiological as well as translational studies, biomarkers are often applied to people under the influence of ketamine. Here, we apply oculomotor, perceptual and cognitive biomarkers to healthy human volunteers whilst they undergo BOLD fMRI at 3 Tesla field strength. We use a counter-balanced, placebo-controlled, double-blind, within-subjects design. A sample of 25 healthy participants is required. Participants will receive intravenous (IV) racemic ketamine (with a 100ng/ml target plasma concentration) on one of two assessment days and they will receive placebo (intravenous saline) on the other assessment day. BOLD fMRI will be carried out on a Siemens Trio scanner at the Life&Brain Centre, Bonn. In addition to brain functional and cognitive, perceptual and oculomotor responses, we will also measure self-ratings of psychosis-like experiences. These will be obtained using the Psychotomimetic States Inventory (PSI; Mason et al 2008).

Official Title
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Effects of Ketamine on Eye Movements, Perception and Brain Function

Conditions
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Functional Neuroimaging

Intervention / Treatment
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* Drug: Ketamine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MRI-suitability suitability for video-based combined pupil and corneal reflection (VCPCR) eye-tracking good command of German language willingness to take part Exclusion Criteria: any current or history of axis I disorder diagnosis as assessed by the Mini-International Neuropsychiatric Interview (M.I.N.I.) any neurological conditions and heart conditions use of any prescription or non-prescription medication up to one week before participation personal history of head-injuries, loss of consciousness, eye surgery or impairment of vision (other than corrective lenses) any other relevant medical conditions such as high blood pressure positive urine drug test (Drug-Screen Multi 5T, nal von minden GmbH) history of drug use or current drug use under- or overweight (below 18.5 and above 24.9 body mass index (BMI) values) any diagnosis of psychotic disorders among first-degree relatives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ketamine-Saline<br>Each participant receives both ketamine and placebo (saline) in randomised order in a repeated-measures design. In this arm, ketamine is administered on the first assessment and placebo (saline) is administered on the second assessment. | Drug: Ketamine<br>* Racemic ketamine, intravenous, at a concentration of 10mg ketamine per 50ml infusion<br>* Other names: Ketamin Ratiopharm;Drug: Saline<br>* Saline, intravenous infusion<br>* Other names: Kochsalzloesung;|
| Other: Saline-Ketamine<br>Each participant receives both ketamine and placebo (saline) in randomised order in a repeated-measures design. In this arm, placebo (saline) is administered on the first assessment and ketamine is administered on the second assessment. | Drug: Ketamine<br>* Racemic ketamine, intravenous, at a concentration of 10mg ketamine per 50ml infusion<br>* Other names: Ketamin Ratiopharm;Drug: Saline<br>* Saline, intravenous infusion<br>* Other names: Kochsalzloesung;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain activity in cortical and subcortical areas as assessed using BOLD (blood oxygen level dependent) functional magnetic resonance imaging (fMRI) at 3 Tesla field strength |  | within 1 hour of start of IV infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychotomimetic State Inventory (PSI) |  | within 1 hour of start of IV infusion | 
| Visual Analogue Rating Scales (VARS) from Norris 1971; self-rating scores of the subscales mental sedation, physical sedation, tranquillisation and other feelings and attitudes |  | within 1 hour of start of IV infusion | 
| d2 Attention Test, a measure of sustained attention | The test requires the crossing out of the letter d combined with two dashes amidst letters d and p combined with one, two, three or four dashes and is a well-established measure of sustained attention | within 1 hour of start of IV infusion | 
| Recognition memory performance (latencies in ms) |  | after 5 days of washout period | 
| Recognition memory performance (percent correct responses) |  | after 5 days of washout period | 
| Smooth pursuit gain (%) |  | within 1 hour of start of IV infusion | 
| Smooth pursuit root mean square error (RMSE) |  | within 1 hour of start of IV infusion | 
| Smooth pursuit saccadic frequency (number per second) |  | within 1 hour of start of IV infusion | 
| Prosaccade latency (ms) |  | within 1 hour of start of IV infusion | 
| Prosaccade gain (%) |  | within 1 hour of start of IV infusion | 
| Prosaccade spatial error (%) |  | within 1 hour of start of IV infusion | 
| Prosaccade velocity (degrees per second) |  | within 1 hour of start of IV infusion | 
| Prosaccade error rate (%) |  | within 1 hour of start of IV infusion | 
| Antisaccade latency (ms) |  | within 1 hour of start of IV infusion | 
| Antisaccade gain (%) |  | within 1 hour of start of IV infusion | 
| Antisaccade spatial error (%) |  | within 1 hour of start of IV infusion | 
| Antisaccade velocity (degrees per second) |  | within 1 hour of start of IV infusion | 
| Antisaccade error rate (%) |  | within 1 hour of start of IV infusion |