Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression

Although depressed mood is a normal occurrence in response to adversity in all individuals, what distinguishes those who are vulnerable to major depressive disorder (MDD) is their inability to effectively regulate negative mood when it arises. Investigating the neural underpinnings of adaptive emotion regulation and the extent to which such processes are compromised in MDD may be helpful in understanding the pathophysiology of depression. We report results from a functional magnetic resonance imaging study demonstrating left-lateralized activation in the prefrontal cortex (PFC) when downregulating negative affect in nondepressed individuals, whereas depressed individuals showed bilateral PFC activation. Furthermore, during an effortful affective reappraisal task, nondepressed individuals showed an inverse relationship between activation in left ventrolateral PFC and the amygdala that is mediated by the ventromedial PFC (VMPFC). No such relationship was found for depressed individuals, who instead show a positive association between VMPFC and amygdala. Pupil dilation data suggest that those depressed patients who expend more effort to reappraise negative stimuli are characterized by accentuated activation in the amygdala, insula, and thalamus, whereas nondepressed individuals exhibit the opposite pattern. These findings indicate that a key feature underlying the pathophysiology of major depression is the counterproductive engagement of right prefrontal cortex and the lack of engagement of left lateral-ventromedial prefrontal circuitry important for the downregulation of amygdala responses to negative stimuli.

Top-down solar modulation of climate: evidence for centennial-scale change

During the descent into the recent ‘exceptionally’ low solar minimum, observations have revealed a larger change in solar UV emissions than seen at the same phase of previous solar cycles. This is particularly true at wavelengths responsible for stratospheric ozone production and heating. This implies that ‘top-down’ solar modulation could be a larger factor in long-term tropospheric change than previously believed, many climate models allowing only for the ‘bottom-up’ effect of the less-variable visible and infrared solar emissions. We present evidence for long-term drift in solar UV irradiance, which is not found in its commonly used proxies. In addition, we find that both stratospheric and tropospheric winds and temperatures show stronger regional variations with those solar indices that do show long-term trends. A top-down climate effect that shows long-term drift (and may also be out of phase with the bottom-up solar forcing) would change the spatial response patterns and would mean that climate-chemistry models that have sufficient resolution in the stratosphere would become very important for making accurate regional/seasonal climate predictions. Our results also provide a potential explanation of persistent palaeoclimate results showing solar influence on regional or local climate indicators.

Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n = 8), lean (fal-, n = 8) and lean (-/-, n = 8)) were characterized via high-resolution H-1 NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fal- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

Bottom-up, not top-down, modulation of imitation by human and robotic models

Visual observation of human actions provokes more motor activation than observation of robotic actions. We investigated the extent to which this visuomotor priming effect is mediated by bottom-up or top-down processing. The bottom-up hypothesis suggests that robotic movements are less effective in activating the ‘mirror system’ via pathways from visual areas via the superior temporal sulcus to parietal and premotor cortices. The top-down hypothesis postulates that beliefs about the animacy of a movement stimulus modulate mirror system activity via descending pathways from areas such as the temporal pole and prefrontal cortex. In an automatic imitation task, subjects performed a prespecified movement (e.g. hand opening) on presentation of a human or robotic hand making a compatible (opening) or incompatible (closing) movement. The speed of responding on compatible trials, compared with incompatible trials, indexed visuomotor priming. In the first experiment, robotic stimuli were constructed by adding a metal and wire ‘wrist’ to a human hand. Questionnaire data indicated that subjects believed these movements to be less animate than those of the human stimuli but the visuomotor priming effects of the human and robotic stimuli did not differ. In the second experiment, when the robotic stimuli were more angular and symmetrical than the human stimuli, human movements elicited more visuomotor priming than the robotic movements. However, the subjects’ beliefs about the animacy of the stimuli did not affect their performance. These results suggest that bottom-up processing is primarily responsible for the visuomotor priming advantage of human stimuli.

Top down influence on visuo-tactile interaction modulates neural oscillatory responses

Multisensory integration involves bottom-up as well as top-down processes. We investigated the influences of top-down control on the neural responses to multisensory stimulation using EEG recording and time-frequency analyses. Participants were stimulated at the index or thumb of the left hand, using tactile vibrators mounted on a foam cube. Simultaneously they received a visual distractor from a light emitting diode adjacent to the active vibrator (spatially congruent trial) or adjacent to the inactive vibrator (spatially incongruent trial). The task was to respond to the elevation of the tactile stimulus (upper or lower), while ignoring the simultaneous visual distractor. To manipulate top-down control on this multisensory stimulation, the proportion of spatially congruent (vs. incongruent) trials was changed across blocks. Our results reveal that the behavioral cost of responding to incongruent than congruent trials (i.e., the crossmodal congruency effect) was modulated by the proportion of congruent trials. Most importantly, the EEG gamma band response and the gamma-theta coupling were also affected by this modulation of top-down control, whereas the late theta band response related to the congruency effect was not. These findings suggest that gamma band response is more than a marker of multisensory binding, being also sensitive to the correspondence between expected and actual multisensory stimulation. By contrast, theta band response was affected by congruency but appears to be largely immune to stimulation expectancy.

Facebook & BlackBoard: comparative view of learning environments

For several years, online educational tools such as Blackboard have been used by Universities to foster collaborative learning in an online setting. Such tools tend to be implemented in a top-down fashion, with the institution providing the tool to the students and instructing them to use it. Recently, however, a more informal, bottom up approach is increasingly being employed by the students themselves in the form of social networks such as Facebook. With over 9,000 registered Facebook users at the beginning of this study, rising to over 12,000 at the University of Reading alone, Facebook is becoming the de facto social network of choice for higher education students in the UK, and there was increasing anecdotal evidence that students were actively learning via Facebook rather than through BlackBoard. To test the validity of these anecdotes, a questionnaire was sent to students, asking them about their learning experiences via BlackBoard and Facebook. The results show that students are making use of the tools available to them even when there is no formal academic content, and that increased use of a social networking tool is correlated with a reported increase in learning as a result of that use.

Refashioning local government and inner-city regeneration: The Salford experience

This paper explores the role of local government in urban regeneration in England. The first part describes local-central government relations during recent decades. It concludes that 'actually occurring' regeneration fuses top-down and bottom-up priorities and preferences, as well as path dependencies created by past decisions and local relations. The second part illustrates this contention by examining the regeneration of inner-city Salford over a 25-year period. It describes Salford City Council's approach in achieving the redevelopment of the former Salford Docks and how this created the confidence for the council to embark on further regeneration projects. Yet the top-down decision-making model has failed to satisfy local expectations, creating apathy which threatens the Labour government's desire for active citizens in regeneration projects.

Social interactions and resource ownership in two private protected areas of Paraguay

This paper describes the results of field research to dissect how social interactions differ between two reserves in Paraguay having very different styles of governance. The two reserves were Mbaracayu Natural Forest Reserve (Reserva Natural del Bosque de Mbaracayti, RNBM) and San Rafael Managed Resource Reserve (Reserva de Recursos Manejados San Rafael, RRMSR). RNBM is a private reserve owned by a non-governmental organisation. while RRNISR is a publicly-managed reserve, albeit with a substantial degree of private land ownership. Both reserves are intended to protect Atlantic Forest, one of the five world biodiversity 'hotspots', and also one of the most highly threatened. Each reserve and its buffer zone comprises a set of stakeholders, including indigenous communities and farmers, and the paper explores the interactions between these and the management regime. Indeed, while the management regimes of the two reserves are different, one being highly top-down (RNBM) and the other more socially inclusive (RRMSR), the issues that they have to deal with are much the same. However, while both management regimes will readily acknowledge the need to address poverty, inequality appears to be a far more sensitive issue. Whereas this may be expected for the privately-owned RNBM it is perhaps more surprising in RRNISR even when allowing for the fact that much of the land in the latter is in private hands. It is argued that the origins of this sensitivity rest within the broader features of Paraguayan society, and the prevalence of private land ownership. Yet ironically, it is the inequality in land ownership that is perhaps the most significant threat to conservation in both reserves. Therefore, while reserve-level analyses can provide some insight into the driving forces at play in the interaction between conservation and sustainable management, larger scales may be necessary to gain a fuller appreciation of the dynamics operating at site level. Even in a society with a history of centralised control these dynamics may be surprising. (c) 2005 Elsevier Ltd. All rights reserved.

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions. Conversely, subjects with greater activation in the ventral lateral prefrontal cortex (VLPFC) in anticipation of pain in the UC versus C conditions reported less pain in response to UC versus C pain. Activation in the VLPFC was significantly correlated with the acceptance and denial subscales of the COPE inventory [Carver, C. S., Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically based approach. Journal of Personality and Social Psychology, 56, 267–283, 1989], supporting the interpretation that this anticipatory activation was associated with an attempt to cope with the emotional impact of uncontrollable pain. A regression model containing the two prefrontal clusters (VLPFC and pACC) predicted 64% of the variance in pain rating difference, with activation in the two additional regions (PAG and insula/SII) predicting almost no additional variance. In addition to supporting the conclusion that the impact of perceived controllability on pain perception varies highly between individuals, these findings suggest that these effects are primarily top-down, driven by processes in regions of the prefrontal cortex previously associated with cognitive modulation of pain and emotion regulation.

Viewing the body modulates tactile receptive fields

Tactile discrimination performance depends on the receptive field (RF) size of somatosensory cortical (SI) neurons. Psychophysical masking effects can reveal the RF of an idealized "virtual" somatosensory neuron. Previous studies show that top-down factors strongly affect tactile discrimination performance. Here, we show that non-informative vision of the touched body part influences tactile discrimination by modulating tactile RFs. Ten subjects performed spatial discrimination between touch locations on the forearm. Performance was improved when subjects saw their forearm compared to viewing a neutral object in the same location. The extent of visual information was relevant, since restricted view of the forearm did not have this enhancing effect. Vibrotactile maskers were placed symmetrically on either side of the tactile target locations, at two different distances. Overall, masking significantly impaired discrimination performance, but the spatial gradient of masking depended on what subjects viewed. Viewing the body reduced the effect of distant maskers, but enhanced the effect of close maskers, as compared to viewing a neutral object. We propose that viewing the body improves functional touch by sharpening tactile RFs in an early somatosensory map. Top-down modulation of lateral inhibition could underlie these effects.

Dynamical evolution of the 2003 southern hemisphere stratospheric winter using Envisat trace-gas observations

Data from the MIPAS instrument on Envisat, supplemented by meteorological analyses from ECMWF and the Met Office, are used to study the meteorological and trace-gas evolution of the stratosphere in the southern hemisphere during winter and spring 2003. A pole-centred approach is used to interpret the data in the physically meaningful context of the evolving stratospheric polar vortex. The following salient dynamical and transport features are documented and analysed: the merger of anticyclones in the stratosphere; the development of an intense, quasi-stationary anticyclone in spring; the associated top-down breakdown of the polar vortex; the systematic descent of air into the polar vortex; and the formation of a three-dimensional structure of a tracer filament on a planetary scale. The paper confirms and extends existing paradigms of the southern hemisphere vortex evolution. The quality of the MIPAS observations is seen to be generally good. though the water vapour retrievals are unrealistic above 10 hPa in the high-latitude winter.

Solar induced climate effects

Solar electromagnetic radiation powers Earth’s climate system and, consequently, it is often naively assumed that changes in this solar output must be responsible for changes in Earth’s climate. However, the Sun is close to a blackbody radiator and so emits according to its surface temperature and the huge thermal time constant of the outer part of the Sun limits the variability in surface temperature and hence output. As a result, on all timescales of interest, changes in total power output are limited to small changes in effective surface temperature (associated with magnetic fields) and potential, although as yet undetected, solar radius variations. Larger variations are seen in the UV part of the spectrum which is emitted from the lower solar atmosphere (the chromosphere) and which influences Earth’s stratosphere. There is interest in“top-down” mechanisms whereby solar UV irradiance modulates stratospheric temperatures and winds which, in turn, may influence the underlying troposphere where Earth’s climate and weather reside. This contrasts with “bottom-up” effects in which the small total solar irradiance (dominated by the visible and near-IR) variations cause surface temperature changes which drive atmospheric circulations. In addition to these electromagnetic outputs, the Sun modulates energetic particle fluxes incident on the Earth. Solar Energetic Particles (SEP) are emitted by solar flares and from the shock fronts ahead of supersonic (and super-Alfvenic) ejections of material from the solar atmosphere. These SEPs enhance the destruction of polar stratospheric ozone which could be an additional form of top-down climate forcing. Even more energetic are Galactic Cosmic Rays (GCRs). These particles are not generated by the Sun, rather they originate at the shock fronts emanating from violent galactic events such as supernovae explosions; however, the expansion of the solar magnetic field into interplanetary space means that the Sun modulates the number of GCRs reaching Earth. These play a key role in enabling Earth’s global electric (thunderstorm) circuit and it has been proposed that they also modulate the formation of clouds. Both electromagnetic and corpuscular solar effects are known to vary over the solar magnetic cycle which is typically between 10 and 14 yrs in length (with an average close to 11 yrs). The solar magnetic field polarity at any one phase of one of these activity cycles is opposite to that at the same phase of the next cycle and this influences some phenomena, for example GCRs, which therefore show a 22 yr (“Hale”) cycle on average. Other phenomena, such as irradiance modulation, do not depend on the polarity of the magnetic field and so show only the basic 11-yr activity cycle. However, any effects on climate are much more significant for solar drifts over centennial timescales. This chapter discusses and evaluates potential effects on Earth’s climate system of variations in these solar inputs. Because of the great variety of proposed mechanisms, the wide range of timescales studied (from days to millennia) and the many debates (often triggered by the application of inadequate statistical methods), the literature on this subject is vast, complex, divergent and rapidly changing: consequently the number of references cited in this review is very large (yet still only a small fraction of the total).

Direct estimates of emissions from the megacity of Lagos

We report here top-down emissions estimates for an African megacity. A boundary layer circumnavigation of Lagos, Nigeria was completed using the FAAM BAe146 aircraft as part of the AMMA project. These observations together with an inferred boundary layer height allow the flux of pollutants to be calculated. Extrapolation gives annual emissions for CO, NOx, and VOCs of 1.44 Tg yr−1, 0.03 Tg yr−1 and 0.37 Tg yr−1 respectively with uncertainties of +250/−60%. These inferred emissions are consistent with bottom-up estimates for other developing megacities and are attributed to the evaporation of fuels, mobile combustion and natural gas emissions.

The income requirements of marine protected areas

Given the growing impact of human activities on the sea, managers are increasingly turning to marine protected areas (MPAs) to protect marine habitats and species. Many MPAs have been unsuccessful, however, and lack of income has been identified as a primary reason for failure. In this study, data from a global survey of 79 MPAs in 36 countries were analysed and attempts made to construct predictive models to determine the income requirements of any given MPA. Statistical tests were used to uncover possible patterns and relationships in the data, with two basic approaches. In the first of these, an attempt was made to build an explanatory "bottom-up" model of the cost structures that might be required to pursue various management activities. This proved difficult in practice owing to the very broad range of applicable data, spanning many orders of magnitude. In the second approach, a "top-down" regression model was constructed using logarithms of the base data, in order to address the breadth of the data ranges. This approach suggested that MPA size and visitor numbers together explained 46% of the minimum income requirements (P < 0.001), with area being the slightly more influential factor. The significance of area to income requirements was of little surprise, given its profile in the literature. However, the relationship between visitors and income requirements might go some way to explaining why northern hemisphere MPAs with apparently high incomes still claim to be under-funded. The relationship between running costs and visitor numbers has important implications not only in determining a realistic level of funding for MPAs, but also in assessing from where funding might be obtained. Since a substantial proportion of the income of many MPAs appears to be utilized for amenity purposes, a case may be made for funds to be provided from the typically better resourced government social and educational budgets as well as environmental budgets. Similarly visitor fees, already an important source of funding for some MPAs, might have a broader role to play in how MPAs are financed in the future. (C) 2007 Elsevier Ltd. All rights reserved.

Building synergies in development research: The application of the mosaic model to animal health research

Development research has responded to a number of charges over the past few decades. For example, when traditional research was accused of being 'top-down', the response was participatory research, linking the 'receptors' to the generators of research. As participatory processes were recognised as producing limited outcomes, the demand-led agenda was born. In response to the alleged failure of research to deliver its products, the 'joined-up' model, which links research with the private sector, has become popular. However, using examples from animal-health research, this article demonstrates that all the aforementioned approaches are seriously limited in their attempts to generate outputs to address the multi-faceted problems facing the poor. The article outlines a new approach to research: the Mosaic Model. By combining different knowledge forms, and focusing on existing gaps, the model aims to bridge basic and applied findings to enhance the efficiency and value of research, past, present, and future.