In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.
Posttraumatic stress disorder (PTSD) affects 5-10% of the general U.S. population at some point during their lifetime; however, the prevalence in much higher among certain subgroups, including active duty military personnel and veterans. Pharmacotherapy of PTSD has made little headway on the past two decades. Methylphenidate (Ritalin®) is a stimulant drug that amplifies dopaminergic and noradrenergic signaling in the brain. Dopamine and norepinephrine are thought to play a critical role during fear extinction by moderating medial prefrontal cortex (mPFC) activity. The magnitude of mPFC activity seems to crucially affect the degree of fear extinction. The model of fear extinction is one approach to conceptualize PTSD. Thereby a previously neutral stimulus is paired with a highly aversive unconditioned stimulus. Fear extinction refers to the decrement in that conditioned fear responses that occur with repeated presentation of the conditioned neutral fear stimulus without the aversive stimulus. While preclinical data suggest that a single dose of methylphenidate enhances fear extinction, it is less clear how methylphenidate affects fear extinction in humans. However, exposing PTSD patients to new therapies is difficult. In the present study, investigator will investigate the effects of methylphenidate (40 mg) on mPFC activity in healthy male volunteers during fear extinction using functional magnetic resonance imaging (fMRI). Additionally, investigators will examine the effects of methylphenidate during aversive interoceptve arousal. The present study will help to identify brain structures and networks involved in anxiety and will give insights for methylphenidate as a possible adjunct to behavioral therapy for patients with anxiety disorders. Further, this study may provide important information about the possible use of fMRI to help the development of drugs for the treatment of anxiety disorders.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
24
UCSD Psychiatry Clinical Research
San Diego, California, United States
Changes in blood oxygenation level-dependent BOLD signal responses
Methylphenidate-induced changes in BOLD signal responses in brain regions relevant in fear disorders (e.g. amygdala, insula, and prefrontal cortex) during a fear extinction task compared to placebo.
Time frame: 6 hours
Changes in BOLD signal responses
Methylphenidate induced changes in BOLD signal responses in regions implicated in emotional processing while anticipating a positive interoceptive stimulus compared to placebo.
Time frame: 6 hours
Changes in skin conductance response
Changes compared to placebo in skin conductance respo during a fear extinction task
Time frame: 6 hours
Latency and accuracy during a interoceptive stimulus task
This task aims to examine the participants' response to an aversive interoceptive stimulus. Individuals will perform a simple continuous performance task during the paradigm. Subjects are asked to press one of three buttons to rate the images on the screen as either 'dislike', 'neutral' or 'like'. Both accuracy and response latency (ms) will be recorded to determine effects of anticipation and stimulus presentation
Time frame: 2 hours
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