A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: Implications for ADHD and its treatment Articles uri icon

authors

  • DEL CAMPO, NATALIA
  • FRYER, TIM D.
  • HONG, YOUNG T.
  • SMITH, ROB
  • BRICHARD, LAURENT
  • ACOSTA-CABRONERO, JULIO
  • CHAMBERLAIN, SAMUEL R.
  • TAIT, ROGER
  • IZQUIERDO GARCÍA, DAVID
  • REGENTHAL, RALF
  • DOWSON, JONATHAN
  • SUCKLING, JOHN
  • BARON, JEAN-CLAUDE
  • AIGBIRHIO, FRANKLIN I.
  • ROBBINS, TREVOR W.
  • SAHAKIAN, BARBARA J.
  • MÜLLER, ULRICH

published in

publication date

  • November 2013

start page

  • 3252

end page

  • 3270

issue

  • 11

volume

  • 136

International Standard Serial Number (ISSN)

  • 0006-8950

Electronic International Standard Serial Number (EISSN)

  • 1460-2156

abstract

  • Through the combined use of 18F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder.

subjects

  • Biology and Biomedicine

keywords

  • attention deficit/hyperactivity disorder; 18f-fallypride pet; dopamine; methylphenidate; sustained attention