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The effects of methylphenidate on cerebral activations to salient stimuli in healthy adults.

ABSTRACT: Detection of a salient stimulus is critical to cognitive functioning. A stimulus is salient when it appears infrequently, carries high motivational value, and/or when it dictates changes in behavior. Individuals with neurological conditions that implicate altered catecholaminergic signaling, such as those with attention deficit hyperactivity disorder, are impaired in detecting salient stimuli, a deficit that can be remediated by catecholaminergic medications. However, the effects of these catecholaminergic agents on cerebral activities during saliency processing within the context of the stop-signal task are not clear. Here, we examined the effects of a single oral dose (45 mg) of methylphenidate in 24 healthy adults performing the stop-signal task during functional MRI (fMRI). Compared to 92 demographically matched adults who did not receive any medications, the methylphenidate group showed higher activations in bilateral caudate head, primary motor cortex, and the right inferior parietal cortex during stop as compared to go trials (p < .05, corrected for family-wise error of multiple comparisons). These results show that methylphenidate enhances saliency processing by promoting specific cerebral regional activities. These findings may suggest a neural basis for catecholaminergic treatment of attention disorders.

SUBMITTER: Farr OM

PROVIDER: S-EPMC4105943 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesViloxazine extended-release (viloxazine ER, SPN-812) is a novel non-stimulant with activity at serotonin receptors and the norepinephrine transporter, which is under investigation as a potential treatment for attention-deficit/hyperactivity disorder. Given the potential for viloxazine ER to be coadministered with other pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine ER + methylphenidate versus viloxazine ER or methylphenidate alone.MethodsIn this single-center, crossover, open-label trial, healthy adult participants received oral administration of 700 mg viloxazine ER alone, 36 mg methylphenidate alone, and combination viloxazine ER (700 mg) + methylphenidate (36 mg), with blood samples collected over 4 days post-administration. The active drug in viloxazine ER (viloxazine) and methylphenidate was measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events (AEs), vital signs, echocardiograms, and clinical laboratory evaluations.ResultsOf 36 healthy adults who were enrolled, 34 completed the trial. The geometric least squares mean ratios are reported as [combination/single drug (90% confidence intervals)]. For viloxazine ER, maximum measured plasma concentration (Cmax) = 100.98% (96.21-105.99), area under the concentration-time curve from time zero to the last measurable time (AUCt) = 98.62% (96.21-101.08), and area under the concentration-time curve from time zero to infinity (AUC∞) = 98.96% (96.55-101.44). For methylphenidate, Cmax = 103.55% (97.42-110.07), AUCt = 106.67% (101.01-112.64), and AUC∞ = 106.61% (100.99-112.54). All reported AEs were mild in severity.ConclusionsCoadministration of viloxazine ER and methylphenidate did not impact the pharmacokinetics of viloxazine or methylphenidate relative to administration of either drug alone. The combination appeared to be safe and well tolerated.

Project description:Humans perceive snakes as threatening stimuli, resulting in fast emotional and behavioral responses. However, snake species differ in their true level of danger and are highly variable in appearance despite the uniform legless form. Different snakes may evoke fear or disgust in humans, or even both emotions simultaneously. We designed three-step-selection experiments to identify prototypical snake species evoking exclusively fear or disgust. First, two independent groups of respondents evaluated 45 images covering most of the natural variability of snakes and rated responses to either perceived fear (n = 175) or disgust (n = 167). Snakes rated as the most fear-evoking were from the family Viperidae (Crotalinae, Viperinae, and Azemiopinae), while the ones rated as the most disgusting were from the group of blind snakes called Typhlopoidea (Xenotyphlopinae, Typhlopinae, and Anomalepidinae). We then identified the specific traits contributing to the perception of fear (large body size, expressive scales with contrasting patterns, and bright coloration) and disgust (thin body, smooth texture, small eyes, and dull coloration). Second, to create stimuli evoking a discrete emotional response, we developed a picture set consisting of 40 snakes with exclusively fear-eliciting and 40 snakes with disgust-eliciting features. Another set of respondents (n = 172) sorted the set, once according to perceived fear and the second time according to perceived disgust. The results showed that the fear-evoking and disgust-evoking snakes fit mainly into their respective groups. Third, we randomly selected 20 species (10 fear-evoking and 10 disgust-evoking) out of the previous set and had them professionally illustrated. A new set of subjects (n = 104) sorted these snakes and confirmed that the illustrated snakes evoked the same discrete emotions as their photographic counterparts. These illustrations are included in the study and may be freely used as a standardized assessment tool when investigating the role of fear and disgust in human emotional response to snakes.

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The effects of methylphenidate on cerebral activations to salient stimuli in healthy adults.

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