title: Anatomical connection strength predicts dopaminergic drug effects on fronto-striatal function.
abstract: BACKGROUND
  The neurotransmitter dopamine plays a key role in cognitive functions that are associated with fronto-striatal circuitry and has been implicated in many neuropsychiatric disorders. However, there is a large variability in the direction and extent of dopaminergic drug effects across individuals.
  
  
  OBJECTIVE
  We investigated whether individual differences in dopaminergic drug effects on human fronto-striatal functioning are associated with individual differences in white matter tracts.
  
  
  METHODS
  The effects of the dopamine receptor agonist bromocriptine were assessed using functional magnetic resonance imaging in 22 healthy volunteers in a placebo-controlled, double-blind, within-subject design. Human psychopharmacology and functional neuroimaging were combined with functional connectivity analyses and structural connectivity analyses to establish a link between dopaminergic drug effects on fronto-striatal function and fronto-striatal anatomy.
  
  
  RESULTS
  We demonstrate that bromocriptine alters functional signals associated with attention switching in the basal ganglia. Crucially, individual differences in the drug's effect on these signals could be predicted from individual differences in fronto-striato-thalamic white matter tracts, as indexed by diffusion tensor imaging. Anatomical fronto-striatal connectivity also predicted drug effects on switch-related functional connectivity between the basal ganglia and the prefrontal cortex.
  
  
  CONCLUSIONS
  These data reinforce the link between dopamine, cognition and the basal ganglia and have implications for the individual tailoring of dopaminergic drug therapy based on anatomical fronto-striatal connection strength.
authors: Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, and Department of Psychiatry, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. m.vanschouwenburg@donders.ru.nl
authors: Martine R
authors: MR
authors: van Schouwenburg
authors: Marcel P
authors: MP
authors: Zwiers
authors: Marieke E
authors: ME
authors: van der Schaaf
authors: Dirk E M
authors: DE
authors: Geurts
authors: Arnt F A
authors: AF
authors: Schellekens
authors: Jan K
authors: JK
authors: Buitelaar
authors: Robbert J
authors: RJ
authors: Verkes
authors: Roshan
authors: R
authors: Cools
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects; D001931:Brain Mapping; D001971:Bromocriptine / Q000493:pharmacokinetics / Q000494:pharmacology*; D003342:Corpus Striatum / Q000033:anatomy & histology* / Q000187:drug effects* / Q000378:metabolism; D056324:Diffusion Tensor Imaging; D018491:Dopamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011954:Receptors, Dopamine / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D001971:Bromocriptine
references: Nature. 2011 May 15;474(7351):372-5
references: 21572439
references: Nat Neurosci. 2005 Jun;8(6):805-12
references: 15908948
references: Neuroimage. 2006 May 1;30(4):1077-87
references: 16635579
references: Cogn Affect Behav Neurosci. 2004 Dec;4(4):580-99
references: 15849899
references: J Neurosci. 2007 Jun 6;27(23):6219-23
references: 17553994
references: J Neurosci. 2009 Feb 4;29(5):1538-43
references: 19193900
references: Biol Psychiatry. 2011 Jun 15;69(12):e113-25
references: 21531388
references: Neuroimage. 2009 Oct 1;47(4):1974-81
references: 19477281
references: Neuroimage. 2010 Nov 1;53(2):565-75
references: 20600997
references: Neuroimage. 2002 May;16(1):177-99
references: 11969328
references: Brain. 2003 Aug;126(Pt 8):1767-81
references: 12805106
references: NMR Biomed. 2002 Nov-Dec;15(7-8):435-55
references: 12489094
references: Neuropsychopharmacology. 2010 Aug;35(9):1943-51
references: 20463658
references: PLoS Biol. 2009 Aug;7(8):e1000170
references: 19668354
references: J Neurosci. 2009 Aug 12;29(32):10171-9
references: 19675251
references: J Cereb Blood Flow Metab. 2010 Sep;30(9):1551-7
references: 20571517
references: IEEE Trans Med Imaging. 2000 Nov;19(11):1115-27
references: 11204849
references: Curr Biol. 2007 Aug 21;17(16):1426-31
references: 17689962
references: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12212-7
references: 16103359
references: J Cogn Neurosci. 2007 Jul;19(7):1081-8
references: 17583985
references: Neuroimage. 2002 Jan;15(1):273-89
references: 11771995
references: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17951-6
references: 19822738
references: Neuroimage. 1997 Oct;6(3):218-29
references: 9344826
references: J Neurosci. 2010 Oct 20;30(42):14205-12
references: 20962241
references: Cogn Affect Behav Neurosci. 2005 Jun;5(2):212-21
references: 16180627
references: Prog Neurobiol. 2004 Sep;74(1):1-58
references: 15381316
references: J Neurosci. 2009 Mar 25;29(12):3695-704
references: 19321766
references: Cereb Cortex. 2014 Mar;24(3):633-42
references: 23183711
references: Front Hum Neurosci. 2011 Mar 31;5:32
references: 21503140
references: Neuroimage. 2007 Jan 1;34(1):144-55
references: 17070705
references: Neuroimage. 2007 Jul 1;36(3):511-21
references: 17499520
references: Philos Trans R Soc Lond B Biol Sci. 2007 Sep 29;362(1485):1601-13
references: 17428778
references: J Neurosci. 2008 Sep 24;28(39):9790-6
references: 18815263
references: J Neurosci. 2007 May 16;27(20):5506-14
references: 17507572
references: J Neurosci. 2008 Apr 2;28(14):3697-706
references: 18385328
references: Nat Neurosci. 2009 May;12(5):535-40
references: 19396166
references: Curr Pharm Des. 2006;12(20):2487-500
references: 16842172
references: Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13240-5
references: 20622155
references: PLoS One. 2010 Nov 04;5(11):e13848
references: 21079814
references: J Neurosci. 2010 Jul 21;30(29):9910-8
references: 20660273
references: J Neurosci. 2007 Apr 4;27(14):3743-52
references: 17409238
references: Psychopharmacology (Berl). 2005 Aug;180(4):644-53
references: 16001111
references: Neuroreport. 1997 Nov 10;8(16):3581-5
references: 9427330
references: Annu Rev Neurosci. 1986;9:357-81
references: 3085570
references: J Neurosci. 2008 Jun 4;28(23):5976-82
references: 18524902
references: Neuron. 2010 Jul 29;67(2):294-307
references: 20670836