Propranololbehandling vid schizofreni

Six schizophrenic patients were treated with propranolol in order to evaluate pharmacological, endocrinological and antipsychotic properties of the drug. They had previously been unsuccessfully treated with phenothiazines.

After a drug-free period of two weeks, propranolol was administered in gradually increasing doses. After 2–4 weeks phenothiazines in a low dose was added. The clinical effect was evaluated with the CPRS rating scale. Propranolol in plasma was positively correlated to dosage. The proportion of its major metabolite, 4-hydroxy-propranolol, decreased with increasing drug dose.

Serotonin in whole blood and monoamine-oxidase activity in platelets did not change during propranolol treatment.

Melatonin and prolactin levels in serum decreased markedly on propranolol. When phenothiazines were added, prolactin increased above drug-free levels. These results support the view that propranolol has an antipsychotic potential which should be further evaluated in clinical trials and possibly also used for the elucidation of biological correlates to psychoses.     

Expectation affects neural repetition suppression in infancy

Recent work provides evidence that the infant brain is able to make top-down predictions, but this has been explored only in limited contexts and domains. We build upon this evidence of predictive processing in infants using a new paradigm to examine auditory repetition suppression (RS). RS is a well-documented neural phenomenon in which repeated presentations of the same stimulus result in reduced neural activation compared to non-repeating stimuli. Many theories explain RS using bottom-up mechanisms, but recent work has posited that top-down expectation and predictive coding may bias, or even explain, RS. Here, we investigate whether RS in the infant brain is similarly sensitive to top-down mechanisms. We use fNIRS to measure infants’ neural response in two experimental conditions, one in which variability in stimulus presentation is expected (occurs 75% of the time) and a control condition where variability and repetition are equally likely (50% of the time). We show that 6-month-old infants exhibit attenuated frontal lobe response to blocks of variable auditory stimuli during contexts when variability is expected as compared to the control condition. These findings suggest that young infants’ neural responses are modulated by predictions gained from experience and not simply by bottom-up mechanisms.     

The kynurenine pathway and cognitive performance in community-dwelling older adults. The Hordaland Health Study

IntroductionTryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults.MethodsThis cross-sectional study included 2174 participants aged 70–72 years of the community-based Hordaland Health Study. Tryptophan, kynurenine, neopterin and eight downstream kynurenines were measured in plasma. Kendrick Object Learning Test (KOLT), Digit Symbol Test (DST) and the Controlled Oral Word Association Test (COWAT) were all outcomes in standardized Zellner’s regression. The Wald test of a composite linear hypothesis of an association with each metabolite was adjusted by the Bonferroni method. Age, body mass index, C-reactive protein, depressive symptoms, diabetes, education, glomerular filtration rate, hypertension, previous myocardial infarction, prior stroke, pyridoxal 5′phosphate, sex and smoking were considered as potential confounders.ResultsHigher levels of the kynurenine-to-tryptophan ratio (KTR) and neopterin were significantly associated with poorer, overall cognitive performance (p < 0.002). Specifically, KTR was negatively associated with KOLT (β −0.08, p = 0.001) and COWAT (β −0.08, p = 0.001), but not with DST (β −0.03, p = 0.160). This pattern was also seen for neopterin (KOLT: β −0.07; p = 0.001; COWAT: β −0.06, p = 0.010; DST: β −0.01, p = 0.800). The associations were not confounded by the examined variables. No significant associations were found between the eight downstream kynurenines and cognition.ConclusionHigher KTR and neopterin levels, biomarkers of cellular immune activation, were associated with reduced cognitive performance, implying an association between the innate immune system, memory, and language.     

Effets de l’huile des fruits de Dacryodes edulis sur les symptômes de l’anxiété et les performances cognitives chez la souris,après administration prolongée

ObjectiveTo study the effects of prolonged administration of Dacryodes edulis (G. Don) H.J. Lam (HDE) fruit oil on the symptoms of anxiety and cognitive performance in mice.MethodsAnxiolytic activity and effects of HDE (5 and 10 ml/kg) on cognitive performance were evaluated in male mice after oral administration for 45 days. Anxiolytic effects were investigated in open field test, elevated plus Maze and hole board test. The Morris Water Maze test was used to evaluate cognitive performance in mice. Efficacy of HDE (5 and 10 ml/kg) was compared with that of fluoxetine (2 mg/kg p.o).ResultsHDE decreases the total distance traveled, significantly increases the number of adjustments and the number of entries in the central area of open field. In the elevated cross labyrinth test, HDE increases the number of entries and the time spent in the open arms. HDE significantly increases the number of head insertion into the holes. In the Morris Water Maze test, HDE reduces latency before finding the platform and increases the time spent in the target quadrant.ConclusionThe results confirm anxiolytic effects and improved cognitive performance after prolonged oral administration of HDE in rodents.     

Comparison of PC and iPad administrations of the Cogstate Brief Battery in the Mayo Clinic Study of Aging: Assessing cross-modality equivalence of computerized neuropsychological tests

Objective: Computerized neuropsychological assessments are increasingly used in clinical practice, population studies of cognitive aging and clinical trial enrichment. Subtle, but significant, performance differences have been demonstrated across different modes of test administration and require further investigation.

Method: Participants included cognitively unimpaired adults aged 50 and older from the Mayo Clinic Study of Aging who completed the Cogstate Brief Battery and Cogstate’s Groton Maze Learning Test (GMLT) on an iPad or a personal computer (PC) in the clinic. Mode of administration differences and test–retest reliability coefficients were examined across 3 cohorts: a demographically matched test–retest cohort completing PC and iPad administrations the same day (N?=?168); a test naïve cohort comparing baseline PC (n?=?1820) and iPad (n?=605) performance; and a demographically matched longitudinal cohort completing 3 Cogstate visits over 15 months on either the PC (n?=63) or iPad (n?=63).

Results: Results showed a small but statistically significant and consistent finding for faster performance on PC relative to iPad for several Cogstate Brief Battery measures. Measures of accuracy generally did not differ or differences were very small. The GMLT showed faster performance and higher total errors on iPad. Most Cogstate variables showed no difference in the rate of change across PC and iPad administrations.

Conclusions: There are small, but significant, differences in performance when giving the same cognitive tests on a PC or an iPad. Future studies are needed to better understand if these small differences impact the clinical interpretation of results and research outcomes.     

Automated and manual segmentation of the hippocampus in human infants

The hippocampus, critical for learning and memory, undergoes substantial changes early in life. Investigating the developmental trajectory of hippocampal structure and function requires an accurate method for segmenting this region from anatomical MRI scans. Although manual segmentation is regarded as the “gold standard” approach, it is laborious and subjective. This has fueled the pursuit of automated segmentation methods in adults. However, little is known about the reliability of these automated protocols in infants, particularly when anatomical scan quality is degraded by head motion or the use of shorter and quieter infant-friendly sequences. During a task-based fMRI protocol, we collected quiet T1-weighted anatomical scans from 42 sessions with awake infants aged 4–23 months. Two expert tracers first segmented the hippocampus in both hemispheres manually. The resulting inter-rater reliability (IRR) was only moderate, reflecting the difficulty of infant segmentation. We then used four protocols to predict these manual segmentations: average adult template, average infant template, FreeSurfer software, and Automated Segmentation of Hippocampal Subfields (ASHS) software. ASHS generated the most reliable hippocampal segmentations in infants, exceeding the manual IRR of experts. Automated methods thus provide robust hippocampal segmentations of noisy T1-weighted infant scans, opening new possibilities for interrogating early hippocampal development.