A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment
A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment
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 D 2/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.
Attention deficit/hyperactivity disorder, Dopamine, Methylphenidate, Sustained attention
3252-3270
Del Campo, Natalia
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Fryer, Tim D.
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Hong, Young T.
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Smith, Rob
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Brichard, Laurent
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Acosta-Cabronero, Julio
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Chamberlain, Samuel R.
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Tait, Roger
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Izquierdo, David
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Regenthal, Ralf
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Dowson, Jonathan
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Suckling, John
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Baron, Jean Claude
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Aigbirhio, Franklin I.
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Robbins, Trevor W.
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Sahakian, Barbara J.
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Müller, Ulrich
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1 November 2013
Del Campo, Natalia
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Fryer, Tim D.
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Hong, Young T.
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Smith, Rob
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Brichard, Laurent
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Acosta-Cabronero, Julio
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Chamberlain, Samuel R.
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Tait, Roger
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Izquierdo, David
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Regenthal, Ralf
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Dowson, Jonathan
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Suckling, John
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Baron, Jean Claude
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Aigbirhio, Franklin I.
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Robbins, Trevor W.
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Sahakian, Barbara J.
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Müller, Ulrich
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Del Campo, Natalia, Fryer, Tim D., Hong, Young T., Smith, Rob, Brichard, Laurent, Acosta-Cabronero, Julio, Chamberlain, Samuel R., Tait, Roger, Izquierdo, David, Regenthal, Ralf, Dowson, Jonathan, Suckling, John, Baron, Jean Claude, Aigbirhio, Franklin I., Robbins, Trevor W., Sahakian, Barbara J. and Müller, Ulrich
(2013)
A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.
Brain, 136 (11), .
(doi:10.1093/brain/awt263).
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 D 2/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.
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Published date: 1 November 2013
Keywords:
Attention deficit/hyperactivity disorder, Dopamine, Methylphenidate, Sustained attention
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Local EPrints ID: 492576
URI: http://eprints.soton.ac.uk/id/eprint/492576
ISSN: 0006-8950
PURE UUID: 572b7387-1003-4f12-9b19-2bb0f05b52c2
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Date deposited: 06 Aug 2024 16:46
Last modified: 07 Aug 2024 01:59
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Contributors
Author:
Natalia Del Campo
Author:
Tim D. Fryer
Author:
Young T. Hong
Author:
Rob Smith
Author:
Laurent Brichard
Author:
Julio Acosta-Cabronero
Author:
Samuel R. Chamberlain
Author:
Roger Tait
Author:
David Izquierdo
Author:
Ralf Regenthal
Author:
Jonathan Dowson
Author:
John Suckling
Author:
Jean Claude Baron
Author:
Franklin I. Aigbirhio
Author:
Trevor W. Robbins
Author:
Barbara J. Sahakian
Author:
Ulrich Müller
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