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Title: Methylphenidate Decreased the Amount of Glucose Needed by the Brain to Perform a Cognitive Task

Journal Article · · PLoS ONE
 [1];  [2];  [2];  [3];  [2];  [2];  [3];  [2];  [2];  [4]
  1. National Inst. on Drug Abuse, Bethesda, MD (United States); National Inst. on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). Medical Dept.
  3. National Inst. on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)
  4. Univ. of California, Irvine, CA (United States). Child Development Center

The use of stimulants (methylphenidate and amphetamine) as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose) in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations) given with and without methylphenidate (20 mg, oral). Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less). This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate’s reduction of the metabolic increases in regions from the default network (implicated in mind-wandering) was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a ‘‘focusing’’ of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering) or impaired (i.e., attention deficit hyperactivity disorder), but it could be detrimental when brain activity is already optimally focused. This would explain why methylphenidate has beneficial effects in some individuals and contexts and detrimental effects in others.

Research Organization:
Associated Universities, Inc., Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-76CH00016
OSTI ID:
1627345
Journal Information:
PLoS ONE, Vol. 3, Issue 4; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Drug Regimen Individualization for Attention‐Deficit/Hyperactivity Disorder: Guidance for Methylphenidate and Dexmethylphenidate Formulations
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  • Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Vol. 39, Issue 6 https://doi.org/10.1002/phar.2190
journal November 2018
Non-specific effects of methylphenidate (Ritalin) on cognitive ability and decision-making of ADHD and healthy adults journal April 2010
Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study journal December 2011
Methylphenidate administration promotes sociability and reduces aggression in a mouse model of callousness journal April 2019
Oral Methylphenidate Normalizes Cingulate Activity and Decreases Impulsivity in Cocaine Addiction During an Emotionally Salient Cognitive Task journal November 2010
Methylphenidate’s effects on thalamic metabolism and functional connectivity in cannabis abusers and healthy controls journal December 2018
Association between striatal dopamine D2/D3 receptors and brain activation during visual attention: effects of sleep deprivation journal May 2016
Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients journal July 2010
Nonmedical Prescription Stimulant Use Among College Students: Why We Need to Do Something and What We Need to Do journal September 2010
Methylphenidate Enhances Executive Function and Optimizes Prefrontal Function in Both Health and Cocaine Addiction journal November 2012
Cocaine Decreases Spontaneous Neuronal Activity and Increases Low-Frequency Neuronal and Hemodynamic Cortical Oscillations journal April 2018
ADHD symptoms map onto noise-driven structure-function decoupling between hub and peripheral brain regions posted_content January 2019
Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate: Default mode network modulation in ADHD journal November 2010
Differential therapeutic effects of atomoxetine and methylphenidate in childhood attention deficit/hyperactivity disorder as measured by near-infrared spectroscopy journal May 2017
Methylphenidate as a cognitive enhancer in healthy young people journal June 2016
Biomarkers for attention-deficit/hyperactivity disorder (ADHD). A consensus report of the WFSBP task force on biological markers and the World Federation of ADHD journal July 2012
Obesity Management: What Should We Do If Fat Gain Is Necessary to Maintain Body Homeostasis in a Modern World? journal June 2018
Sedentariness and Health: Is Sedentary Behavior More Than Just Physical Inactivity? journal September 2018
ADHD symptoms map onto noise-driven structure–function decoupling between hub and peripheral brain regions journal October 2019
An investigation into aripiprazole’s partial D2 agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers journal February 2016
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Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention journal June 2009
Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers journal July 2010
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Elevated Background Noise in Adult Attention Deficit Hyperactivity Disorder Is Associated with Inattention journal February 2015
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Effects of the 2-Repeat Allele of the DRD4 Gene on Neural Networks Associated With the Prefrontal Cortex in Children With ADHD journal July 2018
Absent without leave; a neuroenergetic theory of mind wandering journal January 2013

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