Response of the multiple-demand network during simple stimulus discriminations

The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control

Hierarchical Representation of Multistep Tasks in Multiple-Demand and Default Mode Networks

Task episodes consist of sequences of steps that are performed to achieve a goal. We used fMRI to examine neural representation of task identity, component items, and sequential position, focusing on two major cortical systems—the multipledemand (MD) and default mode networks (DMN). Human participants (20 males, 22 females) learned six tasks each consisting of four steps. Inside the scanner, participants were cued which task to perform and then sequentially identified the target item of each step in the correct order. Univariate time course analyses indicated that intra-episode progress was tracked by a tonically increasing global response, plus an increasing phasic step response specific to MD regions. Inter-episode boundaries evoked a widespread response at episode onset, plus a marked offset response specific to DMN regions. Representational similarity analysis (RSA) was used to examine representation of task identity and component steps. Both networks represented the content and position of individual steps, however the DMN preferentially represented task identity while the MD network preferentially represented step-level information. Thus, although both MD and DMN networks are sensitive to step-level and episode-level information in the context of hierarchical task performance, they exhibit dissociable profiles in terms of both temporal dynamics and representational content. The results suggest collaboration of multiple brain regions in control of multistep behavior, with MD regions particularly involved in processing the detail of individual steps, and DMN adding representation of broad task context

The Functional Convergence and Heterogeneity of Social, Episodic, and Self-Referential Thought in the Default Mode Network

The default mode network (DMN) is engaged in a variety of cognitive settings, including social, semantic, temporal, spatial, and self-related tasks. Andrews-Hanna et al. (2010; Andrews-Hanna 2012) proposed that the DMN consists of three distinct functional–anatomical subsystems—a dorsal medial prefrontal cortex (dMPFC) subsystem that supports social cognition; a medial temporal lobe (MTL) subsystem that contributes to memory-based scene construction; and a set of midline core hubs that are especially involved in processing self-referential information. We examined activity in the DMN subsystems during six different tasks: 1) theory of mind, 2) moral dilemmas, 3) autobiographical memory, 4) spatial navigation, 5) self/other adjective judgment, and 6) a rest condition. At a broad level, we observed similar whole-brain activity maps for the six contrasts, and some response to every contrast in each of the three subsystems. In more detail, both univariate analysis and multivariate activity patterns showed partial functional separation, especially between dMPFC and MTL subsystems, though with less support for common activity across the midline core. Integrating social, spatial, self-related, and other aspects of a cognitive situation or episode, multiple components of the DMN may work closely together to provide the broad context for current mental activity

Magnetic structure and spin-wave excitations in the multiferroic magnetic metal-organic framework (CD3)(2)ND2[Mn(DCO2)(3)]

The authors thank STFC for the award of beam time at ISIS Neutron and Muon Source. A.E.P. is grateful to EPSRC for funding (EP/L024977/1

Global coordination of transcriptional control and mRNA decay during cellular differentiation

We have systematically identified the targets of the Schizosaccharomyces pombe RNA-binding protein Meu5p, which is transiently induced during cellular differentiation. Meu5p-bound transcripts (>80) are expressed at low levels and have shorter half-lives in meu5 mutants, suggesting that Meu5p binding stabilizes its RNA targets.Most Meu5p targets are induced during differentiation by the activity of the Mei4p transcription factor. However, although most Mei4p targets display a sharp peak of expression, Meu5p targets are expressed for a longer period. In the absence of Meu5p, all Mei4p targets are expressed with similar kinetics (similar to non-Meu5p targets). Therefore, Meu5p determines the temporal profile of its targets.As the meu5 gene is itself a target of the transcription factor Mei4p, the RNA-binding protein Meu5p and their shared targets form a feed-forward loop (FFL), a network motif that is common in transcriptional networks.Our data highlight the importance of considering both transcriptional and posttranscriptional controls to understand dynamic changes in RNA levels, and provide insight into the structure of the regulatory networks that integrate transcription and RNA decay

Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson's Disease Cohort (ICICLE-PD).

BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (β = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (β = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families

Cognitive impairment in Parkinson's disease: impact on quality of life of carers.

BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. METHODS: Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. RESULTS: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01). CONCLUSIONS: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd

Cooperation and Contagion in Web-Based, Networked Public Goods Experiments

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and &gt;18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (&gt;21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption