Are there Sex Differences in Confidence and Metacognitive Monitoring Accuracy for Everyday, Academic, and Psychometrically Measured Spatial Ability?

The current study evaluated sex differences in (1) self-perceptions of everyday and academic spatial ability, and (2) metacognitive monitoring accuracy for measures of spatial visualization and spatial orientation. Undergraduate students completed the Paper Folding Test, Spatial Relations Test, and the Revised Purdue Spatial Visualization Test while making confidence judgments (CJs) for each trial. They also made global estimates of performance and rated their ability to perform several everyday and academic spatial scenarios. Across multiple spatial measures, female students displayed lower confidence in their item-level monitoring and global assessments of performance than did male students, even when no actual differences in spatial performance occurred. Women were also less confident in their self-assessments of their visualspatial ability for scientific domains than were men. However, the absolute and relative accuracy of CJs did not differ as a function of sex suggesting that women can monitor their spatial performance as well as men.

Pharmacokinetic Characterization of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in Urine Following Acute Oral Cannabis Ingestion in Healthy Adults.

Understanding the urine excretion profile for Δ9-tetrahydrocannabinol (THC) metabolites is important for accurate detection and interpretation of toxicological testing for cannabis use. Prior literature has primarily evaluated the urinary pharmacokinetics of the non-psychoactive THC metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) following smoked cannabis administration. The present study examined the urine THCCOOH excretion profile following oral cannabis administration in 18 healthy adults. Following ingestion of a cannabis-containing brownie with 10, 25 or 50 mg of THC (N = 6 per dose), urine specimens were collected on a closed residential research unit for 6 days, followed by three outpatient visits on Days 7-9. Average maximum concentrations (Cmax) of THCCOOH were 107, 335 and 713 ng/mL, and average times to maximum concentration (Tmax) were 8, 6 and 9 h for the 10, 25 and 50 mg THC doses, respectively. Detection windows to first positive and last positive varied as a function of dose; higher doses had shorter time to first positive and longer time to last positive. Considerable inter-subject variability was observed on study outcomes. Gas chromatography/mass spectrometry (GC/MS; 15 ng/mL cutoff) was used as the criterion to assess sensitivity, specificity and agreement for THCCOOH qualitative immunoassay tests using 20, 50 and 100 ng/mL cutoffs. The 50 ng/mL cutoff displayed good sensitivity (92.5%), specificity (92.4%) and overall agreement (92.4%), whereas the 20 ng/mL cutoff demonstrated poor specificity (58.4%), and the 100 ng/mL cutoff exhibited reduced sensitivity (70.9%). Ingestion of cannabis brownies containing the 10 and 25 mg THC doses yielded THCCOOH concentrations that differed in magnitude and time course from those previously reported for the smoked route of administration of comparable doses.

Chemogenetic locus coeruleus activation restores reversal learning in a rat model of Alzheimer's disease.

See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer's disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies. Here, a transgenic rat (TgF344-AD) expressing disease-causing mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1ΔE9) was characterized for histological and behavioural signs of locus coeruleus dysfunction reminiscent of mild cognitive impairment/early Alzheimer's disease. In TgF344-AD rats, hyperphosphorylated tau was detected in the locus coeruleus prior to accrual in the medial entorhinal cortex or hippocampus, and tau pathology in the locus coeruleus was negatively correlated with noradrenergic innervation in the medial entorhinal cortex. Likewise, TgF344-AD rats displayed progressive loss of hippocampal norepinephrine levels and locus coeruleus fibres in the medial entorhinal cortex and dentate gyrus, with no frank noradrenergic cell body loss. Cultured mouse locus coeruleus neurons expressing hyperphosphorylation-prone mutant human tau had shorter neurites than control neurons, but similar cell viability, suggesting a causal link between pretangle tau accrual and altered locus coeruleus fibre morphology. TgF344-AD rats had impaired reversal learning in the Morris water maze compared to their wild-type littermates, which was rescued by chemogenetic locus coeruleus activation via designer receptors exclusively activated by designer drugs (DREADDs). Our results indicate that TgF344-AD rats uniquely meet several key criteria for a suitable model of locus coeruleus pathology and dysfunction early in Alzheimer's disease progression, and suggest that a substantial window of opportunity for locus coeruleus/ norepinephrine-based therapeutics exists.