An integrative approach to determine the best behavioral and biological markers of methylphenidate.
OBJECTIVE
To distinguish the most sensitive markers of methylphenidate (MPH) effects on behavior and underlying biology using an integrated cognitive and brain function test battery.


METHODS
A randomized placebo-controlled trial with 32 healthy adult males. Subjects were tested on MPH doses across 18 sessions with subjective mood, objective behavioral and biological endpoints. From a computerized battery of tests, behavioral measures were cognitive performance scores, while biological measures of brain function included electroencephalographs (EEG) and event-related potentials (ERPs) with complementary measures of autonomic arousal. Using mixed modeling analyses; we determined which measures were most affected by MPH dose and correlation analyses determined the associations among them.


RESULTS
MPH dose had the most pronounced effect on cognitive performance (sustained attention/vigilance), baseline autonomic arousal (heart rate, blood pressure) and baseline brain activity (EEG theta power). The faster reaction time, reduced errors, increased autonomic arousal and reductions in theta showed strong to moderate inter-correlations. MPH least affected subjective mood measures and early sensory ERP components.


CONCLUSIONS
These findings suggest that MPH increases cortical and autonomic arousal, facilitating vigilance. The combination of behavioral and biological measures may provide an objective set of markers of MPH response.


CONCLUSIONS
This approach has provided additional insight into the mechanism of the stimulant medication, MPH, which would not be achieved by using such measures in isolation.
Hermens
Daniel F
DF
The Brain Dynamics Center, University of Sydney and Westmead Hospital, Westmead, NSW 2145, Australia. daniel.hermens@brainresource.com
Cooper
Nicholas J
NJ
Clark
C Richard
CR
Debrota
David
D
Clarke
Simon D
SD
Williams
Leanne M
LM
D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D001519:Behavior / Q000187:drug effects*; D015415:Biomarkers; D001921:Brain / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D004311:Double-Blind Method; D004569:Electroencephalography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008606:Mental Processes / Q000187:drug effects*; D008774:Methylphenidate / Q000494:pharmacology*; D009483:Neuropsychological Tests; D011930:Reaction Time / Q000187:drug effects
D015415:Biomarkers; D000697:Central Nervous System Stimulants; D008774:Methylphenidate