Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks

Abstract

ObjectiveAntihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.MethodsIn this double‐blind, placebo‐controlled, three‐way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two‐back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near‐infrared spectroscopy.ResultsEnergy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.ConclusionsPhysiological “coupling” between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.

Validation of the Image Registration Technique from Functional Near Infrared Spectroscopy (fNIRS) Signal and Positron Emission Tomography (PET) Image

“…In Kikuchi et al, 2018, fNIRS signal is superimposed on standard MRI template images to compare the sedative effects of antihistamines in term of cerebral glucose metabolic changes measured by PET and hemodynamic response measured by fNIRS [17]. Therefore, if fNIRS signal could be view on the own subject image, we can view both information in one image of the same subject.…”

Registration of Positron Emission Tomography (PET) Image and Functional Near Infrared Spectroscopy (NIRS) Data

“…3. The details of this study are found in elsewhere [15]. Before the preparation for the NIRS examination, the subject was inserted with normal saline drip into the left antecubital vein.…”

“…It is involving the injection of a radiotracer into human body where the tracer is a biological compound of interest labelled with a positron emitters isotope such as 11 C, 18 F and 15 O [11]. Specific tracers are chosen to illustrate the particular brain functions, for example, 18 F-2-deoxyglucose ( 18 FDG) is used to investigate cerebral glucose metabolism, whereas H2 15 O is used to examine cerebral blood flow [11].…”