Evidencing a place for the hippocampus within the core scene processing network.

Functional neuroimaging studies have identified several "core" brain regions that are preferentially activated by scene stimuli, namely posterior parahippocampal gyrus (PHG), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS). The hippocampus (HC), too, is thought to play a key role in scene processing, although no study has yet investigated scene-sensitivity in the HC relative to these other "core" regions. Here, we characterised the frequency and consistency of individual scene-preferential responses within these regions by analysing a large dataset (n = 51) in which participants performed a one-back working memory task for scenes, objects, and scrambled objects. An unbiased approach was adopted by applying independently-defined anatomical ROIs to individual-level functional data across different voxel-wise thresholds and spatial filters. It was found that the majority of subjects had preferential scene clusters in PHG (max = 100% of participants), RSC (max = 76%), and TOS (max = 94%). A comparable number of individuals also possessed significant scene-related clusters within their individually defined HC ROIs (max = 88%), evidencing a HC contribution to scene processing. While probabilistic overlap maps of individual clusters showed that overlap "peaks" were close to those identified in group-level analyses (particularly for TOS and HC), inter-individual consistency varied across regions and statistical thresholds. The inter-regional and inter-individual variability revealed by these analyses has implications for how scene-sensitive cortex is localised and interrogated in functional neuroimaging studies, particularly in medial temporal lobe regions, such as the HC. Hum Brain Mapp 37:3779-3794, 2016. © 2016 Wiley Periodicals, Inc.

Brain structure correlates of emotion-based rash impulsivity.

Negative urgency (the tendency to engage in rash, ill-considered action in response to intense negative emotions), is a personality trait that has been linked to problematic involvement in several risky and impulsive behaviours, and to various forms of disinhibitory psychopathology, but its neurobiological correlates are poorly understood. Here, we explored whether inter-individual variation in levels of trait negative urgency was associated with inter-individual variation in regional grey matter volumes. Using voxel-based morphometry (VBM) in a sample (n=152) of healthy participants, we found that smaller volumes of the dorsomedial prefrontal cortex and right temporal pole, regions previously linked to emotion appraisal, emotion regulation and emotion-based decision-making, were associated with higher levels of trait negative urgency. When controlling for other impulsivity linked personality traits (sensation seeking, lack of planning/perseverance) and negative emotionality per se (neuroticism), these associations remained, and an additional relationship was found between higher levels of trait negative urgency and smaller volumes of the left ventral striatum. This latter finding mirrors recent VBM findings in an animal model of impulsivity. Our findings offer novel insight into the brain structure correlates of one key source of inter-individual differences in impulsivity.

Evidence against altered excitatory/inhibitory balance in the posteromedial cortex of young adult APOE E4 carriers: A resting state 1H-MRS study.

A strategy to gain insight into early changes that may predispose people to Alzheimer's disease (AD) is to study the brains of younger cognitively healthy people that are at increased genetic risk of AD. The Apolipoprotein (APOE) E4 allele is the strongest genetic risk factor for AD, and several neuroimaging studies comparing APOE E4 carriers with non-carriers at age ∼20-30 years have detected hyperactivity (or reduced deactivation) in posteromedial cortex (PMC), a key hub of the default network (DN), which has a high susceptibility to early amyloid deposition in AD. Transgenic mouse models suggest such early network activity alterations may result from altered excitatory/inhibitory (E/I) balance, but this is yet to be examined in humans. Here we test the hypothesis that PMC fMRI hyperactivity could be underpinned by altered levels of excitatory (glutamate) and/or inhibitory (GABA) neurotransmitters in this brain region. Forty-seven participants (20 APOE E4 carriers and 27 non-carriers) aged 18-25 years underwent resting-state proton magnetic resonance spectroscopy (1H-MRS), a non-invasive neuroimaging technique to measure glutamate and GABA in vivo. Metabolites were measured in a PMC voxel of interest and in a comparison voxel in the occipital cortex (OCC). There was no difference in either glutamate or GABA between the E4 carriers and non-carriers in either MRS voxel, or in the ratio of glutamate to GABA, a measure of E/I balance. Default Bayesian t-tests revealed evidence in support of this null finding. Our findings suggest that PMC hyperactivity in APOE E4 carriers is unlikely to be associated with, or possibly may precede, alterations in local resting-state PMC neurotransmitters, thus informing our understanding of the spatio-temporal sequence of early network alterations underlying APOE E4 related AD risk.

Bioactivity of amphitoxin, the major constituent of the Jamaican sponge Amphimedon compressa.

Fractionation of the MeOH/CH2Cl2 extract of the sponge Amphimedon compressa afforded the secondary metabolite amphitoxin (1), the structure of which was elucidated by interpretation of 1H- and 13C-NMR data. The crude extract and the fractions containing the metabolite 1 were assessed for ichthyotoxic and insecticidal activity towards Xiphophorus variatus (moon fish) and Cylas formicarius elegantulus (sweet potato weevil), respectively. In addition, the ability of 1 to cause mortality (toxicity and lethal effect) in the rodent Rattus norvegicus (Norway rat) was examined. Moderate insecticidal activity was observed, while the toxicity towards the moon fish was evidenced by the high mortality rates for all the fractions tested. In contrast, the rodent was not affected by the metabolite.

Evidence for endogenous opioid release in the amygdala during positive emotion.

Endogenous opioid release has been linked to relief from aversive emotional memories, thereby promoting a euphoric state and subsequent interactions towards social stimuli resulting in the formation of social preferences. However, this theory remains controversial. Using positron emission tomography and [(11)C]diprenorphine (DPN) in healthy volunteers, we found significantly reduced DPN binding to opioid receptor in the hippocampus during positive mood induction compared to neutral mood. Furthermore, the magnitude of positive mood change correlated negatively with DPN binding in the amygdala bilaterally. Our finding of reduced DPN binding is consistent with increased release of endogenous opioids, providing direct evidence that localised release of endogenous opioids is involved in the regulation of positive emotion in humans.

Changes in psychomotor effects of L-dopa and methylphenidate after sustained dopaminergic therapy in Parkinson's disease.

BACKGROUND: Sustained drug therapy in Parkinson's disease may alter the psychomotor responses to acute challenges with dopaminergic drugs, L-dopa and methylphenidate, and cause cross sensitisation. METHODS: The mood, psychomotor and reward potentiating effects of an acute challenge with L-dopa and methylphenidate on separate occasions were assessed under double blind (medication naïve) conditions after a placebo and then the testing sessions were repeated in the same (medication experienced) patients following a median period of 16.7 months of continuous dopaminergic drug therapy. RESULTS: In the medication naïve condition, affect was not changed by L-dopa or methylphenidate and only L-dopa improved motor function. In the medication experienced condition, active drugs improved positive affect compared with the medication naïve condition and there was an enhanced effect of L-dopa on motor function. Reward responsivity was enhanced by both L-dopa and methylphenidate in medication naïve and experienced conditions. CONCLUSION: Sustained dopaminergic drug therapy augments the motor effects of an acute challenge with L-dopa and induces euphoriant effects to L-dopa and methylphenidate challenges.

Extraction, processing, and storage effects on curcuminoids and oleoresin yields from Curcuma longa L. grown in Jamaica.

Aromatic diarylheptanoid compounds from Curcuma longa Linn grown in Jamaica were quantified by UV-vis spectrophotometry and high-performance liquid chromatographic (HPLC) analyses. The oleoresin yields from ethanolic extracts were quantified and evaluated with regard to the effects of the type of postharvesting process and the type of extraction method conducted on the plant material. Fresh samples that were hot solvent extracted provided the highest oleoresin yields of 15.7% +/- 0.4 ( n = 3), and the lowest oleoresin yields of 7.8% +/- 0.2 ( n = 3) were from the dried milled samples that were cold solvent extracted. Data from the ASTA spectrophotometer assay confirmed that dried samples contained the highest curcuminoid content of 55.5% +/- 2.2 ( n = 6) at the fifth month of storage, and the fresh samples showed a curcuminoid content of 47.1% +/- 6.4 ( n = 6) at the third month of storage. A modified HPLC analysis was used to quantify curcumin content. Data from the HPLC analysis confirmed that the dried treated, hot extracted, room temperature stored samples had the highest curcumin content of 24.3%. A novel high-performance thin layer chromatography (HPTLC) method provided a chemical fingerprint of the C. longa with the use of a commercial curcumin standard.

Validation of a PCR-based method for the detection of various rendered materials in feedstuffs using a forensic DNA extraction kit.

A method trial was initiated to validate the use of a commercial DNA forensic kit to extract DNA from animal feed as part of a PCR-based method. Four different PCR primer pairs (one bovine pair, one porcine pair, one ovine primer pair, and one multispecies pair) were also evaluated. Each laboratory was required to analyze a total of 120 dairy feed samples either not fortified (control, true negative) or fortified with bovine meat and bone meal, porcine meat and bone meal (PMBM), or lamb meal. Feeds were fortified with the animal meals at a concentration of 0.1% (wt/wt). Ten laboratories participated in this trial, and each laboratory was required to evaluate two different primer pairs, i.e., each PCR primer pair was evaluated by five different laboratories. The method was considered to be validated for a given animal source when three or more laboratories achieved at least 97% accuracy (29 correct of 30 samples for 96.7% accuracy, rounded up to 97%) in detecting the fortified samples for that source. Using this criterion, the method was validated for the bovine primer because three laboratories met the criterion, with an average accuracy of 98.9%. The average false-positive rate was 3.0% in these laboratories. A fourth laboratory was 80% accurate in identifying the samples fortified with bovine meat and bone meal. A fifth laboratory was not able to consistently extract the DNA from the feed samples and did not achieve the criterion for accuracy for either the bovine or multispecies PCR primers. For the porcine primers, the method was validated, with four laboratories meeting the criterion for accuracy with an average accuracy of 99.2%. The fifth laboratory had a 93.3% accuracy outcome for the porcine primer. Collectively, these five laboratories had a 1.3% false-positive rate for the porcine primer. No laboratory was able to meet the criterion for accuracy with the ovine primers, most likely because of problems with the synthesis of the primer pair; none of the positive control DNA samples could be detected with the ovine primers. The multispecies primer pair was validated in three laboratories for use with bovine meat and bone meal and lamb meal but not with PMBM. The three laboratories had an average accuracy of 98.9% for bovine meat and bone meal, 97.8% for lamb meal, and 63.3% for PMBM. When examined on an individual laboratory basis, one of these four laboratories could not identify a single feed sample containing PMBM by using the multispecies primer, whereas the other laboratory identified only one PMBM-fortified sample, suggesting that the limit of detection for PMBM with this primer pair is around 0.1% (wt/wt). The results of this study demonstrated that the DNA forensic kit can be used to extract DNA from animal feed, which can then be used for PCR analysis to detect animal-derived protein present in the feed sample.

Cognitive functions and corticostriatal circuits: insights from Huntington's disease.

The basic mechanisms of information processing by corticostriatal circuits are currently a matter of intense debate amongst cognitive scientists. Huntington's disease, an autosomal-dominant neurogenetic disorder characterized clinically by a triad of motor, cognitive, and affective disturbance, is associated with neuronal loss within corticostriatal circuits, and as such provides a valuable model for understanding the role of these circuits in normal behaviour, and their disruption in disease. We review findings from our studies of the breakdown of cognition in Huntington's disease, with a particular emphasis on executive functions and visual recognition memory. We show that Huntington's disease patients exhibit a neuropsychological profile that shows a discernible pattern of progression with advancing disease, and appears to result from a breakdown in the mechanisms of response selection. These findings are consistent with recent computational models that suggest that corticostriatal circuits compute the patterns of sensory input and response output which are of behavioural significance within a particular environmental context.

Biological activity and chemical composition of the essential oil from Jamaican Hyptis verticillata Jacq.

The chemical composition of the essential oil obtained by hydrodistillation from the aerial parts of Hyptis verticillata Jacq. was elucidated by a combination of GC and GC-MS analyses. The oil was dominated by the sesquiterpenoids cadina-4,10(15)-dien-3-one (15.1%) (1) and aromadendr-1(10)-en-9-one (squamulosone) (30.7%) (2). The oil exhibited chemosterilant activities against the cattle tick, Boophilus microplus Canest., and toxic action against adult Cylas formicarius elegantulus Summer, the most destructive pest of sweet potato (Ipomoea species).

APOE-ε4 selectively modulates posteromedial cortex activity during scene perception and short-term memory in young healthy adults.

Apolipoprotein E (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), yet the mechanisms by which APOE-ε4 influences early-life brain function, and hence, in turn, risk for later-life AD, are poorly understood. Here, we report a novel, and selective, pattern of functional brain activity alteration in healthy young adult human APOE-ε4 carriers. Our findings suggest that APOE-ε4 may influence vulnerability to poorer later life cognitive health via its effect on posteromedial cortex (PMC), a hub region within a brain network involved in spatial processing, and necessary for episodic memory. In two neuroimaging tasks, APOE-ε4 carriers showed an inability to effectively modulate PMC during scene, but not face and object, working memory and perception. This striking pattern overlaps both functionally and topographically, with the earliest cognitive deficits seen in clinical AD, as well as reported alterations in the default network in amyloid-positive individuals at increased risk of AD.

Discrimination, reversal, and shift learning in Huntington's disease: mechanisms of impaired response selection.

In a series of three experiments, we investigated different aspects of response selection in early-stage clinically symptomatic Huntington's disease (HD) patients in the context of discrimination learning. A series of structurally related response selection tasks involving discrimination, reversal, and shift learning were employed. In Experiment 1, the mechanisms of our previously reported [37] finding of impaired extra-dimensional shift learning were explored. The results suggested that impaired shift learning in HD is a result of perseverative responding. In Experiment 2, performance on a concurrent-pair (CP) discrimination and reversal task was examined. HD patients showed no deficits in CP discrimination learning or reversal. In Experiment 3, the performance of HD patients on a probabilistic discrimination and reversal task was examined. HD patients were impaired in the learning of a probabilistic discrimination, and also its reversal. This reversal deficit was again the result of perseverative responding. In addition, there was a strong correlation between HD patients' activities of daily living scores and reversal errors. The result are consistent with current theories of the role of the basal ganglia in cognition, and suggest specific impairments in response selection mechanisms in HD, in particular, in overcoming selection biases based on prior reinforcement.

Impaired planning but intact decision making in early Huntington's disease: implications for specific fronto-striatal pathology.

Previous neuropsychological data have suggested that deficits in early Huntington's disease (HD) include executive impairments, which often are linked with frontal-lobe dysfunction. This study sought to investigate the profile of cognitive deficits using two computerised tasks whose performance is known to rely on intact functions of separate areas of the prefrontal cortex. Twenty patients with early HD and 20 matched controls were given the one-touch Tower of London, a stringent measure of visuo-spatial planning, and a decision making task, which involved selecting and gambling on outcomes on the basis of their differing probabilities. Patients were significantly less accurate than controls on the planning test, which is sensitive to frontal lobe lesions and is strongly associated with the dorsolateral prefrontal cortex in functional imaging studies. On the decision making task, patients were unimpaired on the quality of their decision making, in contrast to previous reports of impairment on this task in patients with ventromedial prefrontal cortex lesions. This dissociation of performance is discussed in terms of the usual path of progression of HD through the striatum and the resultant pattern of disruption of the functioning of the different cortico-striatal functional loops.

Feedback effects on sequential ordering in humans.

Under various feedback conditions, 38 college undergraduates were asked to rearrange abstract graphic characters on a computer screen, placing them in arbitrarily designated "correct" sequences. Two sets of seven horizontally arrayed stimuli were used. In Experiment 1, subjects in Group 1 learned to arrange the first set under Selection Feedback in which a "+" appeared above each character after it was selected in the correct order and to arrange the second set under Order Feedback in which a correct response produced a copy of the character in its correct ordinal position at the top of the screen. For Group 2 the order of these conditions was reversed. In Experiment 2, for subjects in Group 3, correct responses produced neither of these types of feedback. Subjects in Group 4 received Order Feedback only until the first set was correctly ordered once. Order Feedback was more effective than Selection Feedback during initial acquisition of the first set but not during maintenance; no differences were found for the second set. Only 2 of 9 subjects successfully put the characters in correct sequential order under the No Feedback condition. When, in Experiment 2, Order Feedback was eliminated after the first correctly arranged sequence, the steady-state criteria were met more slowly than in Experiment 1.

Antiproliferative activity and absolute configuration of zonaquinone acetate from the Jamaican alga Stypopodium zonale.

The chemical investigation of specimens of the Jamaican brown alga Stypopodium zonale led to the isolation of a cytotoxic compound, zonaquinone acetate (1), along with known compounds flabellinone, not previously identified in S. zonale, stypoldione, 5',7'-dihydroxy-2'-pentadecylchromone and sargaol. The structures of the metabolites were established by analysis of the spectral data including 1D and 2D NMR experiments while the stereochemistry of 1 was assessed by VCD measurements. Cytotoxic activity was reported in vitro for 1 against breast cancer and colon cancer cell lines at IC(50) values of 19.22-21.62 µM and 17.11-18.35 µM respectively, comparing favorably with standard treatments tamoxifen (17.22-17.32 µM) and fluorouracil (27.03-31.48 µM). When tested with liver cancer cells (Hep G2), no activity was observed. Weak antioxidant activity was observed with 1 but sargaol exhibited high activity.

Chemical composition and biological activity of the essential oil from Jamaican Cleome serrata.

The chemical composition of the essential oil obtained from the aerial parts of Cleome serrata by hydrodistillation was analyzed by employing GC-FID, GC-MS and RI. Fourteen compounds comprising 90.4% of the total oil composition were characterized. The main components identified were (Z)-phytol (53.0%) and di(2-ethylhexyl)-phthalate (DEHP) (14.7%). The oil was evaluated for its in vitro antimicrobial activities against nine pathogenic microorganisms using the filter paper disc diffusion method. Moderate antimicrobial activity was observed against five of the pathogens assayed. In addition, the essential oil was tested against the sweet potato weevil, Cylas formicarius elegantulus. Strong knockdown insecticidal activity was observed.

Chemical composition and antimicrobial activity of the essential oils from Cleome spinosa.

Five different essential oil extractions of the aerial parts of Cleome spinosa Jacq. were examined. The oils obtained by hydrodistillation of the whole aerial parts, aerial parts without flowers (fruit, leaves and stem), flowers, fruits and leaves have been examined by GC-FID and GC-MS. The chemical profiles of the oils reveal the dominance of oxygenated sesqui- and diterpenes, with the exception of the fruit oil, which contained a high content of fatty acids. The most abundant compounds from the whole aerial parts were (Z)-phytol (31.3%), integerrimine (5.5%) and incensole (4.0%). The major compounds from the aerial portion without flowers were caryophyllene oxide (10.5%), (-)-spathulenol (7.5%) and Z-phytol (6.9%). In the flower oil, the main components were 7-alpha-hydroxy manool (23.8%), incensole (9.2%) and sclareol (8.7%). The chief constituents in the fruit oil were tetradecanoic acid (40.6%), (Z)-phytol (6.58%) and sclareol (4.5%). In the leaf oil, (Z)-phytol (19.5%), 7-alpha-hydroxy manool (6.8%) and caryophyllene oxide (4.36%) were the predominant compounds. Antimicrobial activity of the oil obtained from the whole aerial part was evaluated against nine microbial strains using a filter paper disc-diffusion method. The volatile oil showed moderate action against seven of the eight bacteria strains used, with significant inhibitory activity against Streptococcus pyogenes Group A when compared with the standard antibiotics, ampicillin and gentamicin. The fungus, Candida albicans was less sensitive to the essential oil. The oils showed moderate insecticidal activity against Cylas formicarius elegantalus, but possessed no antioxidant activity as indicated by the DPPH method. This represents the first report on the chemical composition of the essential oils from C. spinosa found in Jamaica and the in vitro antioxidant, insecticidal and antimicrobial potential of the oil from the aerial parts.