PET Study Examining Pharmacokinetics, Detection  and Likeability, and Dopamine Transporter Receptor Occupancy of Short- and Long-Acting  Oral Methylphenidate

Spencer, Thomas; Biederman, Joseph; Ciccone, Patrick E.; Dougherty, Darin D.; Bonab, Ali; Livni, Elijahu; Parasrampuria, Dolly A.; Fischman, Alan J.

doi:10.1176/appi.ajp.163.3.387

Cited by 185 publications

(132 citation statements)

References 27 publications

(33 reference statements)

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“…Spencer et al (2006) have subsequently provided confirmatory PET data illustrating how striatal effects of MPH match behavioral effects using immediate and extended release formulations of MPH. Recent study in ADHD adults has also shown depressed dopamine activity in the caudate, and possibly some default network regions (amygdala/hippocampus) were associated with inattention .…”

Section: Functional Studies: Pet and Fmrimentioning

confidence: 92%

“…Both SPECT and PET have generally been supplanted by fMRI for functional studies, as fMRI offers superior spatial and temporal resolution, and SPECT and PET's use of radiopharmaceuticals makes it ethically difficult to justify their use in healthy volunteers, especially children (Castellanos, 2002). However, both SPECT and PET still have important uses that other non-invasive techniques do not offer, such as neurotransmitter receptor characterization, measurement of dopamine transporter (DAT) levels, and quantification of extracellular dopamine Spencer et al, 2006Spencer et al, , 2005Volkow et al, 2005Volkow et al, , 2007. Early SPECT studies suggested striatal/basal ganglia abnormalities (Lou et al, 1984(Lou et al, , 1990(Lou et al, , 1989, despite some methodological issues (Castellanos, 2002).…”

Section: Functional Studies: Pet and Fmrimentioning

confidence: 99%

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Attention-Deficit/Hyperactivity Disorder and Attention Networks

Bush

2009

Neuropsychopharmacol

296

251

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Research attempting to elucidate the neuropathophysiology of attention-deficit/hyperactivity disorder (ADHD) has not only shed light on the disorder itself, it has simultaneously provided new insights into the mechanisms of normal cognition and attention. This review will highlight and integrate this bidirectional flow of information. Following a brief overview of ADHD clinical phenomenology, ADHD studies will be placed into a wider historical perspective by providing illustrative examples of how major models of attention have influenced the development of neurocircuitry models of ADHD. The review will then identify major components of neural systems potentially relevant to ADHD, including attention networks, reward/feedbackbased processing systems, as well as a 'default mode' resting state network. Further, it will suggest ways in which these systems may interact and be influenced by neuromodulatory factors. Recent ADHD imaging data will be selectively provided to both illustrate the field's current level of knowledge and to show how such data can inform our understanding of normal brain functions. The review will conclude by suggesting possible avenues for future research.

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Section: Functional Studies: Pet and Fmrimentioning

confidence: 92%

Section: Functional Studies: Pet and Fmrimentioning

confidence: 99%

Attention-Deficit/Hyperactivity Disorder and Attention Networks

Bush

2009

Neuropsychopharmacol

296

251

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“…PET and SPECT studies have detected NT release in response to pharmacological challenges, including amphetamine (e.g., Dewey et al, 1993;Innis et al, 1992;Laruelle et al, 1995;Mach et al, 1997), cocaine (Mach et al, 1997;Volkow et al, 1999), methylphenidate (Mach et al, 1997;Spencer et al, 2006;Volkow et al, 1999;Volkow et al, 1994) and other drugs, as well as behavioral challenges such as videogaming (Koepp et al, 1998), gambling and monetary reward (Pappata et al, 2002;Zald et al, 2004), and other tasks. In conventional PET analyses, NT release is detected by change in binding potential (BP: e.g., Logan et al, 1996;Logan et al, 1990), an index of the time-averaged decrease in receptor availability from baseline to activation condition.…”

Section: Introductionmentioning

confidence: 99%

“…However, the time course of neurotransmitter release in response to specific stimuli has not been measured in humans and may encode pertinent information about brain function. It has been hypothesized that the speed of dopamine release elicited by a drug may be a strong indicator of the drug's addictive liability and potential for abuse (Spencer et al, 2006;Volkow et al, 1995;Volkow et al, 1999;Volkow and Swanson, 2003). Boileau et al (2007) speculated that amphetamine-and placebo-induced dopamine responses may follow distinct time courses, but noted that PET was not capable of distinguishing such differences.…”

Section: Introductionmentioning

confidence: 99%

Estimating neurotransmitter kinetics with ntPET: A simulation study of temporal precision and effects of biased data

Normandin

Morris

2008

NeuroImage

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We recently introduced ntPET (neurotransmitter PET), an analysis technique which estimates the kinetics of stimulus-induced neurotransmitter (NT) release. Here, we evaluate two formulations of ntPET. The arterial (ART) approach measures the tracer input function (TIF) directly. The reference (REF) approach derives the TIF from reference region data. Arterial sampling is considered the gold standard in PET modeling but reference region approaches are preferred for reduced cost and complexity. If simulated PET data with unbiased TIFs were analyzed using ART or REF, temporal precision was better than three minutes provided NT concentration peaked less than 30 minutes into the scanning session. The consequences of biased TIFs or stimulus-induced changes in tracer delivery were also evaluated. ART TIFs were biased by the presence of uncorrected radiometabolites in the plasma whereas REF TIFs were biased by specific binding in the reference region. Simulated changes in tracer delivery emulated ethanol-induced blood flow alterations observed previously with PET (Volkow et al., 1988). ART performance deteriorated significantly if metabolites amounted to 50% of plasma radioactivity by 60 minutes. The accuracy and precision of REF were preserved even if the reference region contained 40% of the receptor density of the target region. Both methods were insensitive to blood flow alterations (proportional changes in K 1 and k 2 ). Our results suggest that PET data contain information -heretofore not extracted -about the timing of NT release. The REF formulation of ntPET proved to be robust to many plausible model violations and under most circumstances is an appropriate alternative to ART.

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“…One study 7 showed that OROS methylphenidate had no detection or likeability in subjects tested every hour for 10 hours after ingestion.…”

Section: Stimulant Treatmentmentioning

confidence: 99%