Neural implementation of computational mechanisms underlying the continuous trade-off between cooperation and competition.

Social interactions evolve continuously. Sometimes we cooperate, sometimes we compete, while at other times we strategically position ourselves somewhere in between to account for the ever-changing social contexts around us. Research on social interactions often focuses on a binary dichotomy between competition and cooperation, ignoring people's evolving shifts along a continuum. Here, we develop an economic game - the Space Dilemma - where two players change their degree of cooperativeness over time in cooperative and competitive contexts. Using computational modelling we show how social contexts bias choices and characterise how inferences about others' intentions modulate cooperativeness. Consistent with the modelling predictions, brain regions previously linked to social cognition, including the temporo-parietal junction, dorso-medial prefrontal cortex and the anterior cingulate gyrus, encode social prediction errors and context-dependent signals, correlating with shifts along a cooperation-competition continuum. These results provide a comprehensive account of the computational and neural mechanisms underlying the continuous trade-off between cooperation and competition.

The anatomy of apathy: A neurocognitive framework for amotivated behaviour.

Apathy is a debilitating syndrome associated with many neurological disorders, including several common neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, and focal lesion syndromes such as stroke. Here, we review neuroimaging studies to identify anatomical correlates of apathy, across brain disorders. Our analysis reveals that apathy is strongly associated with disruption particularly of dorsal anterior cingulate cortex (dACC), ventral striatum (VS) and connected brain regions. Remarkably, these changes are consistent across clinical disorders and imaging modalities. Review of the neuroimaging findings allows us to develop a neurocognitive framework to consider potential mechanisms underlying apathy. According to this perspective, an interconnected group of brain regions - with dACC and VS at its core - plays a crucial role in normal motivated behaviour. Specifically we argue that motivated behaviour requires a willingness to work, to keep working, and to learn what is worth working for. We propose that deficits in any one or more of these processes can lead to the clinical syndrome of apathy, and outline specific approaches to test this hypothesis. A richer neurobiological understanding of the mechanisms underlying apathy should ultimately facilitate development of effective therapies for this disabling condition.

Contributions of the Medial Prefrontal Cortex to Social Influence in Economic Decision-Making.

Economic decisions are guided by highly subjective reward valuations (SVs). Often these SVs are over-ridden when individuals conform to social norms. Yet, the neural mechanisms that underpin the distinct processing of such normative reward valuations (NVs) are poorly understood. The dorsomedial and ventromedial portions of the prefrontal cortex (dmPFC/vmPFC) are putatively key regions for processing social and economic information respectively. However, the contribution of these regions to economic decisions guided by social norms is unclear. Using functional magnetic resonance imaging and computational modeling we examine the neural mechanisms underlying the processing of SVs and NVs. Subjects (n = 15) indicated either their own economic preferences or made similar choices based on a social norm-learnt during a training session. We found that that the vmPFC and dmPFC make dissociable contributions to the processing of SV and NV. Regions of the dmPFC processed "only" the value of rewards when making normative choices. In contrast, we identify a novel mechanism in the vmPFC for the coding of value. This region signaled both subjective and normative valuations, but activity was scaled positively for SV and negatively for NV. These results highlight some of the key mechanisms that underpin conformity and social influence in economic decision-making.

Reinforcement learning signals in the anterior cingulate cortex code for others' false beliefs.

The ability to recognise that another's belief is false is a hallmark of our capacity to understand others' mental states. It has been suggested that the computational and neural mechanisms that underpin learning about others' mental states may be similar to those that underpin first-person Reinforcement Learning (RL). In RL, unexpected decision-making outcomes constitute prediction errors (PE), which are coded for by neurons in the Anterior Cingulate Cortex (ACC). Does the ACC signal the PEs (false beliefs) of others about the outcomes of their decisions? We scanned subjects using fMRI while they monitored a third-person's decisions and similar responses made by a computer. The outcomes of the trials were manipulated, such that the actual outcome was unexpectedly different from the predicted outcome on 1/3 of trials. We examined activity time-locked to privileged information which indicated the actual outcomes only to subjects. Activity in the gyral ACC was found when the outcomes of the third-person's decisions were unexpectedly positive. Activity in the sulcal ACC was found when the third-person's or computer's outcomes were unexpectedly positive. We suggest that a property of the ACC is that it codes PEs, with a portion of the gyral ACC specialised for processing the PEs of others.

The anterior cingulate cortex: monitoring the outcomes of others' decisions.

The ability to attribute mental states to others and understand the basis of their decisions is essential for human social interaction. A controversial theory states that this is achieved by simulating another's information processing in one's own neural circuits. The anterior cingulate cortex (ACC) is known to play an important role in the registration of discrepancies between the predicted and actual outcomes of decisions (prediction errors).When positive and negative feedback fails altogether, the failure may also signal errors in the prediction that the outcome of that decision would be informative and guide future decisions. Does the ACC signal that an outcome is unexpectedly uninformative? When an outcome directed to others is uninformative, do we understand their mental states by simulating them in the circuits of the ACC in our own brain? The aim of our study was to test for these two possibilities in the human brain with event-related fMRI. We tested whether the ACC processes errors in the prediction of informative feedback and whether the ACC is also activated when scanned subjects process the same outcomes of another's decisions. We show that each is processed by a separate subregion of the ACC.

Cerebellar information processing in relapsing-remitting multiple sclerosis (RRMS).

Recent research has characterized the anatomical connectivity of the cortico-cerebellar system - a large and important fibre system in the primate brain. Within this system, there are reciprocal projections between the prefrontal cortex and Crus II of the cerebellar cortex, which both play important roles in the acquisition and execution of cognitive skills. Here, we propose that this system also plays a particular role in sustaining skilled cognitive performance in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), in whom advancing neuropathology causes increasingly inefficient information processing. We scanned RRMS patients and closely matched healthy subjects while they performed the Paced Auditory Serial Addition Test (PASAT), a demanding test of information processing speed, and a control task. This enabled us to localize differences between conditions that change as a function of group (group-by-condition interactions). Hemodynamic activity in some patient populations with CNS pathology are not well understood and may be atypical, so we avoided analysis strategies that rely exclusively on models of hemodynamic activity derived from the healthy brain, using instead an approach that combined a 'model-free' analysis technique (Tensor Independent Component Analysis, TICA) that was relatively free of such assumptions, with a post-hoc 'model-based' approach (General Linear Model, GLM). Our results showed group-by-condition interactions in cerebellar cortical Crus II. We suggest that this area may have in role maintaining performance in working memory tasks by compensating for inefficient data transfer associated with white matter lesions in MS.

Resilience and vulnerability of northern regions to social and environmental change.

The arctic tundra and boreal forest were once considered the last frontiers on earth because of their vast expanses remote from agricultural land-use change and industrial development. These regions are now, however, experiencing environmental and social changes that are as rapid as those occurring anywhere on earth. This paper summarizes the role of northern regions in the global system and provides a blueprint for assessing the factors that govern their sensitivity to social and environmental change.

Recent patterns and mechanisms of carbon exchange by terrestrial ecosystems.

Knowledge of carbon exchange between the atmosphere, land and the oceans is important, given that the terrestrial and marine environments are currently absorbing about half of the carbon dioxide that is emitted by fossil-fuel combustion. This carbon uptake is therefore limiting the extent of atmospheric and climatic change, but its long-term nature remains uncertain. Here we provide an overview of the current state of knowledge of global and regional patterns of carbon exchange by terrestrial ecosystems. Atmospheric carbon dioxide and oxygen data confirm that the terrestrial biosphere was largely neutral with respect to net carbon exchange during the 1980s, but became a net carbon sink in the 1990s. This recent sink can be largely attributed to northern extratropical areas, and is roughly split between North America and Eurasia. Tropical land areas, however, were approximately in balance with respect to carbon exchange, implying a carbon sink that offset emissions due to tropical deforestation. The evolution of the terrestrial carbon sink is largely the result of changes in land use over time, such as regrowth on abandoned agricultural land and fire prevention, in addition to responses to environmental changes, such as longer growing seasons, and fertilization by carbon dioxide and nitrogen. Nevertheless, there remain considerable uncertainties as to the magnitude of the sink in different regions and the contribution of different processes.

The carbon budget of Canadian forests: a sensitivity analysis of changes in disturbance regimes, growth rates, and decomposition rates.

Ecosystem responses to climate changes will affect the exchange of carbon (C) with the atmosphere, thus providing feedback for future climate response. We have developed a C budget model of Canadian forests and forest sector activities and used sensitivity analysis runs with changes in productivity, decomposition, and disturbance regimes to assess the sensitivity of the Canadian forest sector C budget over the next century. The model operates on data derived from Canada's National Forest Biomass Inventory, from the Oak Ridge National Laboratory global soil C data base, and from Canadian data bases that document areas annually disturbed by fire, insects, and harvesting. It simulates the dynamics of biomass and soil C pools (including detritus and coarse woody debris) as they are affected by growth, decomposition, and disturbances. For the reference run of the model, we assumed unchanging climate and disturbance regimes. Under these conditions, total ecosystem C increased by 2 Gt C (2.3%) over the 100-year simulation period. In the sensitivity analysis, we explored the effects of changes in the area annually disturbed by fire and insect-induced stand mortality (-60 to +300%), growth rates (-10 to +20%), decomposition rates (-10 to +25%), and combined changes in growth and decomposition rates. In every model run, the change of total ecosystem C relative to the reference run was less than 10%. Combined changes to growth and decomposition rates yielded very small deviations from the results of the reference run (-0.8 to +1.2%). Because disturbance regime changes affect forest age-class structure as well as forest dynamics, they are expected to affect C budgets strongly. Total ecosystem C, however, is slightly more sensitive to changes in growth and decomposition parameters than to changes in disturbance regimes. Although the sensitivity analysis results suggest that C budgets are little affected by the range of parameter changes implemented here, we must emphasize that our sensitivity analyses do not account for potentially important processes, such as regeneration failure or the shifts in forest distribution.

A guide to lung function tests.

In patients with respiratory disease, measurement of lung function should be part of the assessment if possible. In the ward, clinic and lung function laboratory there are tests available to examine airflow, lung volume, gas transfer and exercise capacity. These provide information on lung function which may be vital for adequate diagnosis and assessment of the patient.

The value of ear lobe oximetry in the assessment of disability in asbestos-related disease.

Thirty-four asbestos workers, with either asbestosis, diffuse pleural thickening, calcified pleural plaques, or with comparable asbestos exposure but no evidence of asbestos-related disease and seven normal controls underwent a progressive exercise test. The subjects were categorized on the basis of lung function tests and PA chest X-rays. During the exercise test oxygen saturation was measured continuously by an ear lobe oximeter. The asbestosis and diffuse pleural thickening groups showed significant oxygen desaturation on exertion, confirming that both these conditions give rise to appreciable respiratory disability.

Calf blood flow and oxygen carriage after reversal of polycythaemia secondary to hypoxic lung disease.

Reduction of packed cell volume has been recommended as a therapeutic procedure in patients with polycythaemia secondary to hypoxic lung disease. We have investigated the effects of this policy on blood flow and oxygen carriage to the calf in 12 such patients. Packed cell volume was decreased from 0.61 to 0.51 (mean) by isovolaemic haemodilution on a cell separator, with significant reductions in blood viscosity at high and low shear rates. Resting calf blood flow was unchanged but peak flow during reactive hyperaemia increased by 17% and 21% one and seven days after the procedure. Oxygen carriage to the calf at rest was initially unchanged but had fallen by 20% at seven days. During reactive hyperaemia oxygen carriage was not impaired by the reduction in packed cell volume since the rise in blood flow offset any reduction in arterial oxygen content. This study has shown that when blood flow is stressed during reactive hyperaemia oxygen carriage is not compromised by a therapeutic reduction in packed cell volume.

Nocturnal hypoxia and sleep apnoea in asymptomatic obese men.

A disorder of breathing during sleep with a fall in arterial oxygen saturation (%SaO2) and apnoea is reported in association with obesity. In obese women an increased severity of oxygen desaturation and the appearance of sleep apnoea is often seen after the menopause whereas the factors influencing sleep-breathing patterns in obese men are uncertain. We investigated this by studying respiration during sleep in 20 asymptomatic obese men (mean wt 125 kg, age range 18-59 y) and 20 control men of normal weight (mean wt 67 kg, age range 19-67 y). In the obese men the mean awake %SaO2 measured in the supine position was significantly less than controls (obese 95 +/- 0.4, controls 97 +/- 0.2, P less than 0.01) and a greater fall in %SaO2 occurred in this group during sleep (mean asleep %SaO2 obese 90.5 +/- 0.9, controls 96 +/- 0.2, P less than 0.01). In addition, the minimum asleep %SaO2 was significantly less in the obese (mean minimum %SaO2 obese 75 +/- 3, controls 93 +/- 0.9, P less than 0.001). Sleep apnoea was uncommon and infrequent in the controls but was seen in nine obese men and was frequent throughout the night in seven of them. In the obese group increasing age and increasing obesity were not significantly correlated with an increased severity of nocturnal oxygen desaturation. We conclude that disordered sleep-breathing with marked oxygen desaturation and apnoea is a common finding in extremely obese men of all ages and suggest that this results from the mechanical impedence of breathing due to abdominal adipose tissue combined with abnormal central respiratory control.

Respiration and sleep in Parkinson's disease.

Sleep and respiration during sleep were studied in patients with idiopathic Parkinson's disease, patients with Parkinsonism with autonomic disturbance, and normal age and sex matched controls. Patients with idiopathic Parkinson's disease showed significantly reduced REM sleep, and more frequent and prolonged waking throughout the night. Hypoventilation and sleep apnoea did not occur in the idiopathic Parkinson's disease or normal groups, but respiration was disorganised with frequent central and obstructive apnoeas in the autonomic disturbance group. Respiratory rate during non rapid eye movement sleep was similar in the idiopathic Parkinson's disease and normal groups, but patients with idiopathic Parkinson's disease showed tachypnoea awake and during REM sleep.

Rumen papillomas in sheep.

Out of a sample of 200 rumens from sheep slaughtered in Edinburgh, papillomas were found in 25. They occurred as fibro-papillomas, mostly along the pillar of muscle between the dorsal and ventral rumen, and were often multiple. No inclusion bodies were seen in the lesions or papilloma virus particles on electron microscopy. Homogenisation of papillomatous tissue followed by various methods of purification did not yield identifiable virus particles, and viral DNA was not detected. Immunoperoxidase staining showed a very small number of positive cells at or on the surface of 6 out of 10 lesions examined. Thus, it seems probable that virus particles are not found in large numbers in the rumen papillomas of sheep, unlike the situation in ovine skin warts, but are present in a few epithelial cells which are rapidly shed from the surface of the mucous membrane.

Adult onset acid maltase deficiency. Distribution and progression of clinical and pathological abnormality in a family.

The adult onset form of acid maltase deficiency (Type IIb) clinically affects only skeletal muscle. Proximal weakness is more severe in legs than arms and involvement of respiratory muscles is prominent in about a third of the cases. In three siblings with the disease, the severity of limb weakness was related to age and duration of disease. Respiratory muscle involvement was a feature in two of the patients. The pathological abnormality was more marked in quadriceps than deltoid, and was strikingly patchy in distribution within these muscles. In one case, vacuolar change was not evident by light microscopy in two quadriceps biopsies taken 2 years apart. There is thus a spectrum of clinical and pathological expression of the disorder even in a single sibship.

Erythrapheresis compared with placebo apheresis in patients with polycythaemia secondary to hypoxic lung disease.

We have assessed the effects of erythrapheresis, a method of isovolaemic haemodilution, and placebo apheresis in 10 patients with polycythaemia secondary to chronic hypoxic lung disease (Mean PaO2 7.2kPa (54 mm Hg]. The mean packed cell volume decreased from 0.60 to 0.48, with significant decreases in blood viscosity at both high and low shear rates (p less than 0.001). The 6-min walking distance improved after erythrapheresis with no significant placebo effect of the procedure compared to control subjects (p less than 0.01). Erythrapheresis is a safe procedure for packed cell volume reduction. It is associated with clinical improvement and there is no demonstrable placebo effect on exercise tolerance.