The current study aims to investigate the effects of catecholamine modulation by methylphenidate during initial stages of consolidation on memory retention and the underlying neural correlates of memory retrieval.
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Source
Brief title
Condition
- Other condition
Synonym
Health condition
fundamental cognitive neuroscience research of memory consolidation and retention with possible future implications in psychopharmacy and treatment for patients with memory deficits
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1) Memory retention on the associative memory task
At behavioural level, the primary study measure is memory performance,
quantified as the number of correctly learned associative memories and measured
directly at the end of the learning task (Test 1 on Day 1) and on the second
testing day to check long-term memory performance (Test 2 on Day 2). The main
study parameter is the comparison of memory retention (i.e., the difference in
memory performance between Test 1 and 2) between the MPH and placebo group to
test if modulation of catecholamines affects memory retention
2) At neural level, the primary study parameters are activation and functional
connectivity during memory retrieval on the second study day, to test if
modulation of catecholamines is associated with between-group differences in
neural responses to memory retrieval, potentially explaining the behavioral
differences. Furthermore, we will investigate functional connectivity during
resting-state of the MTL and mPFC with each other and with other (neo)cortical
regions.
Secondary outcome
The outcome on three questionnaires will be used as baseline measures of
impulsivity and possible ADHD symptoms. In addition, the outcome of the
Daneman and Carpenter listening span test will be used as a baseline estimate
of working memory capacity, which has been found to be a valid surrogate
measure of catecholamine levels at baseline
Background summary
Adequate memory is essential for normal functioning in daily life. Memory
consolidation refers to the processes that stabilize initially fragile memories
for long-term use. Memory for most experiences fades quickly while memories of
some, usually more significant, events can persist for decades. Release of
catecholamines (noradrenaline and dopamine) during initial stages of
consolidation is thought to underlie this enhanced memory persistence. In
rodents, it has been shown that catecholamine modulation augments memory
retention by influencing consolidation processes. In humans, however, the
effects of catecholamines on memory retention are not yet well investigated.
Also, the mechanistic underpinnings of catecholamine enhanced memory
consolidation are unclear. Methylphenidate (MPH) enhances catecholamine levels
and is currently widely used both as treatment for Attention Deficit
Hyperactivity Disorder (ADHD) as in the healthy student population to improve
study performance.
Study objective
The current study aims to investigate the effects of catecholamine modulation
by methylphenidate during initial stages of consolidation on memory retention
and the underlying neural correlates of memory retrieval.
Study design
A randomized, between-subject, double-blind, placebo-controlled, design will be
employed.
All subjects will visit the Donders Centre for Cognitive Neuroimaging (DCCN)
for one screening session and two testing sessions. During the first testing
session (study Day 1), the subjects will perform a learning task during which
they are instructed to learn the associations between objects and locations.
During this task, 30 subjects will receive an oral capsule of 20mg MPH and 30
subjects will receive an oral placebo capsule. The drug will be administered
halfway during the task to have maximum effect on the consolidation phase after
learning but no effect on learning itself (based on prior studies and
pharmacokinetics). On the second testing day (study Day 2), all subjects will
return and their memory for the learned associations will be tested in a recall
task while measuring brain activity using fMRI. Additionally, brain activity
will be measured during a resting-state period.
The total duration of the experiment is approximately 8 hours per subject,
divided over a screening session (1 hr), study Day 1 (5 hrs) and Day 2 (1,75
hr). The experimental procedures (= study procedures minus the screening
procedures) take place on two days that are 45 to 75 hrs apart.
Intervention
Subjects will receive an oral capsule of 20mg MPH or placebo. These can be
administered safely without any relevant risk of serious adverse events
((S)AEs) and have been approved for clinical use in the Netherlands.
Study burden and risks
Subjects will perform a learning task prior and immediately after
administration of 20mg MPH or placebo. On the second study day, subjects will
perform a recall task while lying in an MRI scanner. On the day preceding the
drug first study day, subjects will have to adhere to some simple restrictions
with respect to alcohol and drug intake. Also, subjects will have to refrain
from smoking and stimulant containing drinks on the morning of the first day.
The most common side effect of taking methylphenidate MPH is mild headache
(occurring in about 10% of people who take the drug). Less common side effects
include feeling dizzy, nauseous or anxious. However, numerous research studies
have demonstrated that 20mg (or more) of MPH is well tolerated in healthy
volunteers between 18 and 35 years of age. Another possible source of
discomfort to participants is the completion of the MRI measurements. Although
the noise and the relative confined space of the MRI scanner may cause
discomfort to some subjects, MRI measurements themselves do not pose any risk,
if appropriate precautions are made.
Considering the extensive exclusion criteria, screening procedure, and constant
monitoring of the subjects we do not expect (S)AEs. The consent discussion
starts sufficiently in advance of the initiation of study-related procedures to
allow potential subjects time to reflect on the potential benefits and risks
and possible discomforts. We estimate the risk associated with participation in
this study as minimal.
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
Healthy right-handed male volunteers between 18 and 35 of age. Normal or corrected-to-normal vision and willingness and ability to sign informed consent
Exclusion criteria
• (History of) psychiatric treatment
• (History of) neurological treatment
• (History of) endocrine treatment
• (History of) autonomic failure (e.g., vasovagal reflex syncope).
• (History of) clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic or pulmonary disease
• Family history of sudden death or ventricular arrhythmia
• (History of) epilepsy
• (History of) drug dependence (opiate, LSD, (meth)amphetamine, cocaine, solvents, or barbiturate) or alcohol dependence
• Family history of schizophrenia or bipolar disorder
• Current or past use of psychotropic medication
• Regular use of corticosteroids.
• Suicidality
• Diabetes
• Uncontrolled hypertension, defined as diastolic blood pressure at rest > 95 mmHg or systolic blood pressure at rest > 180 mmHg
• Hypotension, defined as diastolic blood pressure < 50 mm Hg or systolic < 95 mm Hg or resting pulse rate < 45 beats/min
• Abnormal hearing or (uncorrected) vision.
• Lactose intolerance (placebo pill is a lactose product)
• Irregular sleep/wake rhythm (e.g., regular nightshifts or cross timeline travel).
• Current use of oral medication aside from occasional use of paracetamol
• Use of recreational drugs or alcohol over a period of 24 hours prior to the first study day
• Subjects with any personal characteristics that make him/her ineligible for MR scanning
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL49516.091.14 |