The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder

Abstract Background Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. Methods In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. Results Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. Conclusions The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD

Regularization of Mars Reconnaissance Orbiter CRISM along‐track oversampled hyperspectral imaging observations of Mars

Mars Reconnaissance Orbiter Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) hyperspectral image data have been acquired in an along-track oversampled (ATO) mode with the intent of processing the data to better than the nominal ∼18 m/pixel ground resolution. We have implemented an iterative maximum log-likelihood method (MLM) that utilizes the instrument spectral and spatial transfer functions and includes a penalty function to regularize the data. Products are produced both in sensor space and as projected hyperspectral image cubes at 12 m/pixel. Preprocessing steps include retrieval of surface single scattering albedos (SSA) using the Hapke Function and DISORT-based radiative modeling of atmospheric gases and aerosols. Resultant SSA cubes are despiked to remove extrema and tested to ensure that the remaining data are Poisson-distributed, an underlying assumption for the MLM algorithm implementation. Two examples of processed ATO data sets are presented. ATO0002EC79 covers the route taken by the Curiosity rover during its initial ascent of Mount Sharp in Gale Crater. SSA data are used to model mineral abundances and grain sizes predicted to be present in the Namib barchan sand dune sampled and analyzed by Curiosity. CRISM based results compare favorably to in situ results derived from Curiosity's measurement campaign. ATO0002DDF9 covers Marathon Valley on the Cape Tribulation rim segment of Endeavour Crater. SSA spectra indicate the presence of a minor component of Fe^(3+) and Mg^(2+) smectites on the valley floor and walls. Localization to 12 m/pixel provided the detailed spatial information needed for the Opportunity rover to traverse to and characterize those outcrops that have the deepest absorptions. The combination of orbital and rover-based data show that the smectite-bearing outcrops in Marathon Valley are impact breccias that are basaltic in composition and that have been isochemically altered in a low water to rock environment

Response to a Second Single Antihypertensive Agent Used as Monotherapy for Hypertension After Failure of the Initial Drug

BACKGROUND: An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. OBJECTIVE: To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (<90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. METHODS: We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. RESULTS: Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. CONCLUSIONS: We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.(Arch Intern Med. 1995;155:1757-1762