Cingulo-opercular control network and disused motor circuits joined in standby mode

Whole-brain resting-state functional MRI (rs-fMRI) during 2 wk of upper-limb casting revealed that disused motor regions became more strongly connected to the cingulo-opercular network (CON), an executive control network that includes regions of the dorsal anterior cingulate cortex (dACC) and insula. Disuse-driven increases in functional connectivity (FC) were specific to the CON and somatomotor networks and did not involve any other networks, such as the salience, frontoparietal, or default mode networks. Censoring and modeling analyses showed that FC increases during casting were mediated by large, spontaneous activity pulses that appeared in the disused motor regions and CON control regions. During limb constraint, disused motor circuits appear to enter a standby mode characterized by spontaneous activity pulses and strengthened connectivity to CON executive control regions.

Disuse is a powerful paradigm for inducing plasticity that has uncovered key organizing principles of the human brain (1–4). Monocular deprivation—prolonged covering of one eye—revealed that multiple afferent inputs can compete for representational territory in the primary visual cortex (1). Similar competition between afferents also shapes the somatomotor system. Manipulations such as peripheral nerve deafferentation, whisker trimming, and limb constraint all drive plasticity in the primary somatosensory and motor cortex (2–4). Most plasticity studies to date have used focal techniques, such as microelectrode recordings, to study local changes in brain function. As a result, little is known about how behavior and experience shape the brain-wide functional networks that support complex cognitive operations (5).The brain is composed of networks of regions that cooperate to perform specific cognitive functions (5–8). These functional networks show synchronized spontaneous activity while the brain is at rest, a phenomenon known as resting-state functional connectivity (FC) (9–11). FC can be measured noninvasively in humans using resting-state functional MRI (rs-fMRI) and has been used to parse the brain into canonical functional networks (12, 13), including visual, auditory, and somatomotor networks (14, 15); ventral and dorsal attention networks (8, 16); a default mode network with roles in internally directed cognition and episodic memory (7, 11); a salience network thought to assess the homeostatic relevance of external stimuli (17); a frontoparietal control network supporting error processing and moment-to-moment adjustments in behavior (18–20); and a cingulo-opercular control network (CON), which maintains executive control during goal-directed behavior (18, 19, 21). Each functional network likely carries out a variety of additional functions.A more recent advance in human neuroscience has been the recognition of individual variability in network organization (22–25). Most early rs-fMRI studies examined central tendencies in network organization using group-averaged FC measurements (10, 12, 13). Recent work has demonstrated that functional networks can be identified in an individual-specific manner if sufficient rs-fMRI data are acquired, an approach termed precision functional mapping (PFM) (22, 23, 26–30). PFM respects the unique functional anatomy of each person and avoids averaging together functionally distinct brain regions across individuals.We recently demonstrated that PFM can be used to follow the time course of disuse-driven plasticity in the human brain (31). Three adult participants (Nico, Ashley, and Omar) were scanned at the same time of day for 42 to 64 consecutive days (30 min of rs-fMRI per day) before, during, and after 2 wk of dominant upper-extremity casting (Fig. 1 A and B). Casting caused persistent disuse of the dominant upper extremity during daily behaviors and led to a marked loss of strength and fine motor skill in all participants. During casting, the upper-extremity regions of the left primary somatomotor cortex (L-SM1_ue) and right cerebellum (R-Cblm_ue) functionally disconnected from the remainder of the somatomotor network. Disused motor circuits also exhibited large, spontaneous pulses of activity (Fig. 1C). Disuse pulses did not occur prior to casting, started to occur frequently within 1 to 2 d of casting, and quickly waned after cast removal.Open in a separate windowFig. 1.Experimental design and spontaneous activity pulses. (A) Three participants (Nico, Ashley, and Omar) wore casts covering the entire dominant upper extremity for 2 wk. (B) Participants were scanned every day for 42 to 64 consecutive days before, during, and after casting. All scans included 30 min of resting-state functional MRI. (C) During the Cast period, disused somatomotor circuits exhibited large pulses of spontaneous activity. (C, Left) Whole-brain ANOVA showing which brain regions contained disuse-driven pulses. (C, Right) Time courses of all pulses recorded from the disused primary somatomotor cortex.Somatomotor circuits do not function in isolation. Action selection and motor control are thought to be governed by complex interactions between the somatomotor network and control networks, including the CON (18). Prior studies of disuse-driven plasticity, including our own, have focused solely on somatomotor circuits. Here, we leveraged the whole-brain coverage of rs-fMRI and the statistical power of PFM to examine disuse-driven plasticity throughout the human brain.     

From the Cover: Conflict translates environmental and social risk into business costs

Sustainability science has grown as a field of inquiry, but has said little about the role of large-scale private sector actors in socio-ecological systems change. However, the shaping of global trends and transitions depends greatly on the private sector and its development impact. Market-based and command-and-control policy instruments have, along with corporate citizenship, been the predominant means for bringing sustainable development priorities into private sector decision-making. This research identifies conflict as a further means through which environmental and social risks are translated into business costs and decision making. Through in-depth interviews with finance, legal, and sustainability professionals in the extractive industries, and empirical case analysis of 50 projects worldwide, this research reports on the financial value at stake when conflict erupts with local communities. Over the past decade, high commodity prices have fueled the expansion of mining and hydrocarbon extraction. These developments profoundly transform environments, communities, and economies, and frequently generate social conflict. Our analysis shows that mining and hydrocarbon companies fail to factor in the full scale of the costs of conflict. For example, as a result of conflict, a major, world-class mining project with capital expenditure of between US$3 and US$5 billion was reported to suffer roughly US$20 million per week of delayed production in net present value terms. Clear analysis of the costs of conflict provides sustainability professionals with a strengthened basis to influence corporate decision making, particularly when linked to corporate values. Perverse outcomes of overemphasizing a cost analysis are also discussed.Large-scale natural resource extraction projects (including exploration and processing activities) profoundly transform environments, communities, and economies, and often generate social conflict (2, 3). Previous studies of resource extraction and conflict have highlighted the relationship between mining and hydrocarbon resources and broader civil conflict (4, 5) and individual cases of project level conflict (6, 7). In this study, we investigate the importance of company–community conflict in the context of regulation of the sustainability performance of mining and hydrocarbon companies. We estimate the cost of social conflict to companies, determine how companies interpret this conflict, and explain how they respond to conflict. Costs were understood broadly as the negative impacts of company–community conflict on a company’s tangible and intangible assets, including value erosion. Conflict is defined as the coexistence of aspirations, interests, and world views that cannot be met simultaneously, or that actors do not perceive as being subject to simultaneous satisfaction, and is viewed in this assessment as ranging from low-level tension to escalated situations involving a complete relationship breakdown or violence (8).There is growing appreciation that unmitigated environmental and social risks have the potential to negatively influence the financial success of large-scale developments in the extractive industries. A 2008 study of 190 projects operated by the major international oil companies showed that the time taken for projects to come on-line nearly doubled in the preceding decade, causing significant increases in costs (9), although this increase reflects project remoteness, scale, technical difficulty, and input price, as well as social conflict. A follow-up of a subset of those projects found that nontechnical risks accounted for nearly one-half of the total risks faced by these companies, and that risks related to company relationships with other social actors constituted the single largest category (10). A separate empirical study of 19 publicly traded junior gold-mining companies found two-thirds of the market capitalization of these firms was a function of the firm’s stakeholder engagement practices, whereas only one-third was a function of the value of gold in the ground (11).In its analysis of socio-ecological systems (SESs), the sustainability science literature has said little about the large-scale private sector as an important actor within, and regulator of, SES behavior. A review of the 450 sustainability science articles published in PNAS, for example, finds just 23 referring to “corporate,” “industry,” “private sector,” or “company” in their texts. An extensive word cloud produced by a historical review of 20,000 papers related to sustainability science (12) notes just five terms implying a focus on the private sector (“corporate social,” “corporate sustainability,” “social responsibility,” “industrial ecology,” and “supply chain”), with none of these terms invoking core company decision making, culture, or calculations. However, large-scale corporate actors are obviously of central importance to the “major questions” for research in sustainability science (13), and perhaps especially the questions: “What shapes the long-term trends and transitions that provide the major directions for this century?” and “What determines the adaptability, vulnerability, and resilience of human–environment systems?” (13).The relevance of private sector actors is particularly clear in the extractive industries where, given the evolution of technology and industrial structure in these sectors, large enterprises have become highly influential actors in SES dynamics. Dramatic events and disasters, such as the Deepwater Horizon in the Gulf of Mexico, make this clear. Such enterprises can also be critical actors in slower processes of SES change, such as those mediating the relationships among water, agriculture, livelihoods, mining, and climate change (14, 15). Companies in the extractive industries have, to greater or lesser extent, developed policies for sustainable development and used sustainability professionals to respond to the changes induced by their activities on SESs. It is therefore important to understand the drivers of company behavior to build adequate models of socio-ecological change.This study addresses one potential driver of company behavior: conflicts motivated by the social and environmental risks created by, and the impacts of, corporate activities. More specifically, the study understands social conflict as a means through which populations communicate perceptions of risk and which generate costs for companies. The study refers to risk from the perspective of the entity experiencing the risk (i.e., environmental risks are risks to the environment; social risks are risks to society, social groups, or individuals; and business risks are the risks to the business). We ask about the significance of the costs associated with community conflict to companies, how far companies are prepared to respond to these costs by seeking strategies to reduce the environmental and social risk that they generate within SESs, and the conditions that can induce regulatory and strategic change within the corporate sector itself such that it reduces any negative environmental and social impacts.Although the report addresses just one dimension of large-scale private sector activity, the purpose is to suggest the importance of paying far more attention to corporate behavior in studies of socio-ecological dynamics. Emerging research on large-scale land acquisitions, or “land grabs” (16), and the implications for land-change science (17) suggests the same need to attend to corporate actors in sustainability science. In addressing this theme, our primary purpose is to map out, explore, and identify (rather than test) particular relationships between large-scale business and SES dynamics. The intent of the research is to build SES theory in ways that treat corporate behavior as endogenous to these systems.Through in-depth confidential interviews with corporate finance, legal, and sustainability professionals, and empirical case analysis, we investigate the extent to which recognition of the costs of conflict has the potential to change the ways in which companies address the environmental and social risks of mining and hydrocarbon development. Case studies combined desk-based analysis of secondary materials with key informant interviews to confirm or supplement the analysis. Case studies were used to characterize the types of company–community conflicts affecting mining projects, the point at which conflict took effect within the project cycle, and the types of effects that conflict appeared to have on projects. Key informant interviews were used to address how large-scale mining and hydrocarbon companies interpret these conflicts, how they respond to them, the factors determining different types of company response, and the extent to which calculations of the financial costs of conflict change the ways in which companies respond.     

Prenatal growth in humans and postnatal brain maturation into late adolescence

Prenatal life encompasses a critical phase of human brain development, but neurodevelopmental consequences of normative differences in prenatal growth among full-term pregnancies remain largely uncharted. Here, we combine the power of a within-monozygotic twin study design with longitudinal neuroimaging methods that parse dissociable components of structural brain development between ages 3 and 30 y, to show that subtle variations of the in utero environment, as indexed by mild birth weight (BW) variation within monozygotic pairs, are accompanied by statistically significant (i) differences in postnatal intelligence quotient (IQ) and (ii) alterations of brain anatomy that persist at least into late adolescence. Greater BW within the normal range confers a sustained and generalized increase in brain volume, which in the cortical sheet, is specifically driven by altered surface area rather than cortical thickness. Surface area is maximally sensitive to BW variation within cortical regions implicated in the biology of several mental disorders, the risk for which is modified by normative BW variation. We complement this near-experimental test of prenatal environmental influences on human brain development by replicating anatomical findings in dizygotic twins and unrelated singletons. Thus, using over 1,000 brain scans, across three independent samples, we link subtle differences in prenatal growth, within ranges seen among the majority of human pregnancies, to protracted surface area alterations, that preferentially impact later-maturing associative cortices important for higher cognition. By mapping the sensitivity of postnatal human brain development to prenatal influences, our findings underline the potency of in utero life in shaping postnatal outcomes of neuroscientific and public health importance.     

Does preoperative total parenteral nutrition in patients with ulcerative colitis produce better outcomes?

Purpose

Malnutrition is a frequent problem in patients with ulcerative colitis (UC) leading to increased postoperative complication rates. Preoperative total parenteral nutrition (TPN) has been shown to reduce complications in some subgroups of patients, but has not been studied in UC. We investigated the impact of preoperative TPN on postoperative complication rates in patients undergoing surgery for UC.

Methods

This paper is a review of 235 patients who underwent surgery for UC; 56 received preoperative TPN and 179 did not. Postoperative complication rates were compared.

Results

Both had similar rates of anastomotic leak (5.4 vs. 2.8?%, p?=?0.356), infection (12.5 vs. 20.1?%, p?=?0.199), ileus/bowel obstruction (21.4 vs. 15.6?%, p?=?0.315), cardiac complications (3.6 vs. 0?%, p?=?0.056), wound dehiscence (3.6 vs. 1.7?%, p?=?0.595), reoperation (10.7 vs. 3.9?%, p?=?0.086), and death (1.8 vs. 0?%, p?=?0.238). The TPN group was more malnourished (albumin 2.49 vs. 3.45, p?<?0.001), more often on steroids (83.9 vs. 57.5?%, p?<?0.001), had more emergent surgery (10.7 vs. 3.4?%, p?=?0.029), more severe colitis (89.3 vs. 65.9?%, p?=?0.001), and lower Surgical Apgar Score (6.15 vs. 6.57, p?=?0.033). After controlling for these with logistic regression, the TPN group still had higher complication rates (OR 2.32, p?=?0.04). When line infections were excluded, TPN did not significantly affect outcomes (OR 1.5, p?=?0.311)

Conclusion

There were no differences in postoperative complications when line infections were excluded. Our data does not support routine preoperative TPN in patients with UC. However, it may lead to equal surgical outcomes in the sickest and most malnourished patients at the cost of line-related morbidity.     

Structure–function relationship of working memory activity with hippocampal and prefrontal cortex volumes

A rapidly increasing number of studies are quantifying the system-level network architecture of the human brain based on structural-to-structural and functional-to-functional relationships. However, a largely unexplored area is the nature and existence of “cross-modal” structural–functional relationships, in which, for example, the volume (or other morphological property) of one brain region is related to the functional response to a given task either in that same brain region, or another brain region. The present study investigated whether the gray matter volume of a selected group of structures (superior, middle, and inferior frontal gyri, thalamus, and hippocampus) was correlated with the fMRI response to a working memory task, within a mask of regions previously identified as involved with working memory. The subjects included individuals with schizophrenia, their siblings, and healthy controls (n = 154 total). Using rigorous permutation testing to define the null distribution, we found that the volume of the superior and middle frontal gyri was correlated with working memory activity within clusters in the intraparietal sulcus (i.e., dorsal parietal cortex) and that the volume of the hippocampus was correlated with working memory activity within clusters in the dorsal anterior cingulate cortex and left inferior frontal gyrus. However, we did not find evidence that the identified structure–function relationships differed between subject groups. These results show that long-distance structural–functional relationships exist within the human brain. The study of such cross-modal relationships represents an additional approach for studying systems-level interregional brain networks.     

Production and integrated training of adjectives in three individuals with nonfluent aphasia

Background: Current research in theoretical linguistics, experimental psychology, and clinical aphasiology suggests that adjective training may facilitate unique aspects of language production and functional communication in persons with aphasia. Although considerable research has been devoted to treatments targeting nouns and verbs, there has been relatively little treatment research directed towards adjectives.

Aims: The goal of this study was to further investigate the viability of adjective training in aphasia by applying an integrated treatment approach targeting adjective production in the context of single word, sentence, and discourse levels of communication. Specific objectives were to quantify baseline adjective production, acquisition of target structures, and treatment generalisation effects.

Method: A single-participant multiple-baseline design was used to evaluate treatment effects in three individuals with nonfluent chronic aphasia. A battery of experimental measures and standardised tests was also administered pre- and post-treatment to assess baseline performance and generalisation effects extending to adjectives, other parts of speech, sentence processing, and discourse production.

Outcomes & Results: Two of the three participants acquired the target structures and maintained criterion performance levels 1 month after treatment. In spite of differences in baseline performance and responsiveness to treatment, all three participants demonstrated significant gains on standardised measures of language production.

Conclusions: Findings add to existing literature supporting the viability of adjective training for individuals with aphasia. Participant characteristics and treatment factors that may contribute to variable outcomes are also discussed.