Methylphenidate‐induced activation of the anterior cingulate but not the striatum: A [¹⁵O]H₂O PET study in healthy volunteers

Abstract

The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders, such as schizophrenia, depression, and addiction. (Dys)function of the dopaminergic system may be studied by combining [15O]H2O PET with a dopaminergic drug challenge. In this pilot study we investigated the suitability of the dopamine reuptake blocker methylphenidate (MP) as a dopaminergic probe. Measurements of regional cerebral blood flow (rCBF) were made at 10 and 30 min after placebo and MP (0.25 mg/kg) injection to seven healthy volunteers. During scanning the behavioral condition of the subjects was standardized using a continuous performance task. Growth hormone levels were assessed and subjective ratings were obtained. MP significantly elevated growth hormone levels. After receiving MP, the subjective experience varied from neutral to highly pleasurable. Ten minutes after MP administration, significant relative increases in rCBF were found in the rostral anterior cingulate (AC), temporal poles, and the supplementary motor area. Significant reductions were seen in the superior temporal gyri, right medial frontal gyrus, and right inferior parietal cortex. At 30 min after MP administration, increases were seen in the AC, temporal pole, and right cerebellum. No changes were observed in the striatum. The activation in the right rostral AC was significantly higher in the subjects with the highest euphoria scores compared to the subjects with minimal MP-induced changes in euphoria. We suggest that the combined MP challenge with functional imaging, as described in our study, may be a useful tool to study the functional integrity of the dopaminergic system in psychiatric disorders.

Variability in paralimbic dopamine signaling correlates with subjective responses to d-amphetamine

“…The radiotracer 18 F-fallypride, however, is able to estimate DRD2/3 BPnd in PFC, temporal lobes, and the insula in addition to the striatum (Mukherjee et al , 2002; Riccardi et al , 2008) and can index DA release after d-amphetamine (dAMPH) administration, measured as %ΔBPnd from baseline (Riccardi et al , 2006a; Slifstein et al , 2010). We were particularly interested in using fallypride to test whether DA functions in paralimbic cortical areas, specifically the mPFC/OFC, related to subjective responses to dAMPH given past evidence that activity in these areas are increased in response to psychostimulants in drug naïve individuals (Vollm et al , 2004) and correlate with their self-reported euphoric effects (Udo de Haes et al , 2007). …”

Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study

“…In a spatial working memory task, the MPH-induced improvements in task performance are accompanied by task-related reductions in regional cerebral blood flow (rCBF) in the dorsolateral prefrontal cortex and posterior parietal cortex in healthy males [19] . MPH activates the anterior cingulate but not the striatum according to a [ 15 O]H 2 O PET study in healthy volunteers [20] . There are also some studies in which the MPH effects were evaluated using functional magnetic resonance imaging (fMRI).…”

Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients

“…10 for review). For example, studies have shown that stimulants alter cerebral activation and influence cognitive functions, including improving inhibitory control, in healthy individuals (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Similarly, Overtoom et al (22) reported that methylphenidate improved stopping performance and restored the electrophysiological potential of stopping in a stop signal task, whereas it did not affect go trial reaction time, in adult patients with ADHD.…”