Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task.
Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.
Goldstein
Rita Z
RZ
Department of Medical Research, Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973-5000, USA. rgoldstein@bnl.gov
Woicik
Patricia A
PA
Maloney
Thomas
T
Tomasi
Dardo
D
Alia-Klein
Nelly
N
Shan
Juntian
J
Honorio
Jean
J
Samaras
Dimitris
D
Wang
Ruiliang
R
Telang
Frank
F
Wang
Gene-Jack
GJ
Volkow
Nora D
ND
D000284:Administration, Oral; D000328:Adult; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D003071:Cognition / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage*; D008875:Middle Aged; D009483:Neuropsychological Tests; D013647:Task Performance and Analysis
D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate
J Comp Neurol. 2005 Dec 5;493(1):154-66
16254997
Cognition. 1994 Apr-Jun;50(1-3):7-15
8039375
Clin Rehabil. 2006 Jan;20(1):24-30
16502746
Trends Cogn Sci. 2000 Jun;4(6):215-222
10827444
Annu Rev Neurosci. 2001;24:167-202
11283309
J Neurosci. 2005 Apr 13;25(15):3932-9
15829645
Drug Alcohol Depend. 2003 Aug 20;71(2):207-11
12927659
Physiol Behav. 2002 Dec;77(4-5):477-82
12526986
Am J Psychiatry. 2009 Nov;166(11):1286-94
19755575
Science. 2004 Oct 15;306(5695):443-7
15486290
PLoS One. 2008 Apr 16;3(4):e2017
18414677
Neuropsychiatr Dis Treat. 2008 Dec;4(6):1251-66
19337466
PLoS One. 2010 Jul 09;5(7):e11509
20634975
Biol Psychiatry. 2004 Mar 15;55(6):612-20
15013830
Neuron. 2006 Sep 21;51(6):871-82
16982430
Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14455-9
20660731
Neuroscience. 2007 Feb 23;144(4):1153-9
17197102
Biol Psychiatry. 2008 Oct 1;64(7):636-9
18504036
Neuropsychopharmacology. 2006 Mar;31(3):651-8
16160709
J Head Trauma Rehabil. 2006 Mar-Apr;21(2):107-18
16569985
Curr Opin Neurol. 2006 Dec;19(6):607-12
17102701
Cereb Cortex. 2000 Mar;10(3):206-19
10731217
Biol Psychiatry. 2001 Dec 15;50(12):932-42
11750889
Cereb Cortex. 2003 Feb;13(2):144-54
12507945
Psychiatry Res. 1998 Jun 15;79(2):163-73
9705054
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):688-93
11209066
J Neurosci. 2000 Mar 15;20(6):RC65
10704519
Cogn Affect Behav Neurosci. 2006 Jun;6(2):152-6
17007235
Magn Reson Med. 1995 Sep;34(3):308-12
7500867
Addict Behav. 1998 Jul-Aug;23(4):449-61
9698974
Neuroimage. 2003 Oct;20(2):1411-8
14568510
Am J Psychiatry. 1998 Oct;155(10):1325-31
9766762
Magn Reson Med. 2001 Jul;46(1):6-12
11443704
Nat Rev Drug Discov. 2002 Sep;1(9):710-26
12209151
Nat Rev Neurosci. 2005 Sep;6(9):691-702
16136173
J Neurochem. 1997 May;68(5):2032-7
9109529
J Neurosci. 2003 Jan 1;23(1):12-6
12514195
Drug Alcohol Depend. 1993 Dec;34(1):19-28
8174499
Neuroimage. 2005 Aug 15;27(2):377-86
15893942
Biol Psychiatry. 2007 Jun 15;61(12):1317-9
17556026
Psychol Med. 2008 Feb;38(2):247-56
17825123
Trends Cogn Sci. 2005 Apr;9(4):195-201
15808502
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9453-8
19478067
Biol Psychiatry. 1998 Dec 15;44(12):1219-28
9861465
Am J Psychiatry. 2002 Oct;159(10):1642-52
12359667
Neuroimage. 1997 Nov;6(4):344-52
9417976
Neuroimage. 2008 Feb 1;39(3):1266-73
18024160
J Subst Abuse Treat. 1992;9(3):199-213
1334156
Hum Brain Mapp. 1996;4(1):58-73
20408186
Arch Gen Psychiatry. 2005 Jul;62(7):761-8
15997017
Mol Psychiatry. 2004 Jun;9(6):557-69
15098002
Psychopharmacology (Berl). 2005 Aug;180(4):624-33
15830222
Nat Neurosci. 2008 Apr;11(4):514-20
18311134