EFFECTS OF ASPIRATION VERSUS NEUROTOXIC LESIONS OF THE AMYGDALA ON EMOTIONAL RESPONSES IN MONKEYS

All previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibers of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala to those induced by fiber-sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of Defense, Aggression, Submission, and Approach responses. In unoperated controls, Defense and Approach behaviors were elicited by all four stimuli, "social" and inanimate alike, whereas Aggression and Submission responses occurred only in the presence of the two "social" stimuli. Furthermore, all Defense reactions were reduced with an attractive inanimate item, while Freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioral changes as those with aspiration lesions, namely reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two-thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, since some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fiber damage

Representational specializations of the hippocampus in phylogenetic perspective

In a major evolutionary transition that occurred more than 520 million years ago, the earliest vertebrates adapted to a life of mobile, predatory foraging guided by distance receptors concentrated on their heads. Vision and olfaction served as the principal sensory systems for guiding their search for nutrients and safe haven. Among their neural innovations, these animals had a telencephalon that included a homologue of the hippocampus. Experiments on goldfish, turtles, lizards, rodents, macaque monkeys and humans have provided insight into the initial adaptive advantages provided by the hippocampus homologue. These findings indicate that it housed specialized map-like representations of odors and sights encountered at various locations in an animal’s home range, including the order and timing in which they should be encountered during a journey. Once these representations emerged in early vertebrates, they also enabled a variety of behaviors beyond navigation. In modern rodents and primates, for example, the specialized representations of the hippocampus enable the learning and performance of tasks involving serial order, timing, recency, relations, sequences of events and behavioral contexts. During primate evolution, certain aspects of these representations gained particular prominence, in part due to the advent of foveal vision in haplorhines. As anthropoid primates—the ancestors of monkeys, apes and humans—changed from small animals that foraged locally into large ones with an extensive home range, they made foraging choices at a distance based on visual scenes. Experimental evidence shows that the hippocampus of monkeys specializes in memories that reflect the representation of such scenes, rather than spatial processing in a general sense. Furthermore, and contrary to the idea that the hippocampus functions in memory to the exclusion of perception, brain imaging studies and lesion effects in humans show that its specialized representations support both the perception and memory of scenes and sequences

What We Know and Do Not Know about the Functions of the Orbitofrontal Cortex after 20 Years of Cross-Species Studies

When Pat Goldman-Rakic described the circuitry and function of primate prefrontal cortex in her influential 1987 monograph (Goldman-Rakic, 1987), she included only a few short paragraphs on the orbitofrontal cortex (OFC). That year, there were only nine papers published containing the term “orbitofrontal,” an average of less than one paper per month. Twenty years later, this rate has increased to 32 papers per month. This explosive growth is partly attributable to the remarkable similarities that exist in structure and function across species. These similarities suggest that OFC function can be usefully modeled in nonhuman and even nonprimate species. Here, we review some of these similarities

Guidance for laboratories performing molecular pathology for cancer patients

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here

Action selection in early stages of psychosis: an active inference approach

BACKGROUND: To interact successfully with their environment, humans need to build a model to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case for people with psychosis, disturbs optimal action selection. Recent computational models, such as active inference, have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an active inference framework, we sought to evaluate previous knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls. METHODS: Twenty-three individuals with an at-risk mental state, 26 patients with first-episode psychosis and 31 controls completed a probabilistic task in which action choice (go/no-go) was dissociated from outcome valence (gain or loss). We evaluated group differences in performance and active inference model parameters and performed receiver operating characteristic (ROC) analyses to assess group classification. RESULTS: We found reduced overall performance in patients with psychosis. Active inference modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behaviour, with poorer action-state associations. Importantly, ROC analysis showed fair-to-good classification performance for all groups, when combining modelling parameters and performance measures. LIMITATIONS: The sample size is moderate. CONCLUSION: Active inference modelling of this task provides further explanation for dysfunctional mechanisms underlying decision-making in psychosis and may be relevant for future research on the development of biomarkers for early identification of psychosis

How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans

The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides, indicating that the model developed is of generic relevance to this important microbial community

Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia

Beliefs—attitudes toward some state of the environment—guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia

Accretion of Planetary Material onto Host Stars

Accretion of planetary material onto host stars may occur throughout a star's life. Especially prone to accretion, extrasolar planets in short-period orbits, while relatively rare, constitute a significant fraction of the known population, and these planets are subject to dynamical and atmospheric influences that can drive significant mass loss. Theoretical models frame expectations regarding the rates and extent of this planetary accretion. For instance, tidal interactions between planets and stars may drive complete orbital decay during the main sequence. Many planets that survive their stars' main sequence lifetime will still be engulfed when the host stars become red giant stars. There is some observational evidence supporting these predictions, such as a dearth of close-in planets around fast stellar rotators, which is consistent with tidal spin-up and planet accretion. There remains no clear chemical evidence for pollution of the atmospheres of main sequence or red giant stars by planetary materials, but a wealth of evidence points to active accretion by white dwarfs. In this article, we review the current understanding of accretion of planetary material, from the pre- to the post-main sequence and beyond. The review begins with the astrophysical framework for that process and then considers accretion during various phases of a host star's life, during which the details of accretion vary, and the observational evidence for accretion during these phases.Comment: 18 pages, 5 figures (with some redacted), invited revie

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio