Functional Neuroimaging
Conditions
Brief summary
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
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).
Interventions
DRUGKetamine
Racemic ketamine, intravenous, at a concentration of 10mg ketamine per 50ml infusion
DRUGSaline
Saline, intravenous infusion
Sponsors
University of Bonn
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | within 1 hour of start of IV infusion | 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 |
| 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 | — |
| Psychotomimetic State Inventory (PSI) | 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 | — |
| Prosaccade gain (%) | within 1 hour of start of IV infusion | — |
Countries
Germany
Outcome results
None listed