Dominant hemisphere functional networks compensate for structural connectivity loss to preserve phonological retrieval with aging

Introduction Loss of hemispheric asymmetry during cognitive tasks has been previously demonstrated in the literature. In the context of language, increased right hemisphere activation is observed with aging. Whether this relates to compensation to preserve cognitive function or dedifferentiation implying loss of hemispheric specificity without functional consequence, remains unclear. Methods With a multifaceted approach, integrating structural and functional imaging data during a word retrieval task, in a group of younger and older adults with equivalent cognitive performance, we aimed to establish whether interactions between hemispheres or reorganization of dominant hemisphere networks preserve function. We examined functional and structural connectivity on data from our previously published functional activation study. Functional connectivity was measured using psychophysiological interactions analysis from the left inferior frontal gyrus (LIFG) and the left insula (LINS), based on published literature, and the right inferior frontal gyrus (RIFG) based on our previous study. Results Although RIFG showed increased activation, its connectivity decreased with age. Meanwhile, LIFG and LINS connected more bilaterally in the older adults. White matter integrity, measured by fractional anisotropy (FA) from diffusion tensor imaging, decreased significantly in the older group. Importantly, LINS functional connectivity to LIFG correlated inversely with FA. Conclusions We demonstrate that left hemispheric language areas show higher functional connectivity in older adults with intact behavioral performance, and thus, may have a role in preserving function. The inverse correlation of functional and structural connectivity with age is in keeping with emerging literature and merits further investigation with tractography studies and in other cognitive domains

Default mode network connectivity during task execution.

Initially described as task-induced deactivations during goal-directed paradigms of high attentional load, the unresolved functionality of default mode regions has long been assumed to interfere with task performance. However, recent evidence suggests a potential default mode network involvement in fulfilling cognitive demands. We tested this hypothesis in a finger opposition paradigm with task and fixation periods which we compared with an independent resting state scan using functional magnetic resonance imaging and a comprehensive analysis pipeline including activation, functional connectivity, behavioural and graph theoretical assessments. The results indicate task specific changes in the default mode network topography. Behaviourally, we show that increased connectivity of the posterior cingulate cortex with the left superior frontal gyrus predicts faster reaction times. Moreover, interactive and dynamic reconfiguration of the default mode network regions' functional connections illustrates their involvement with the task at hand with higher-level global parallel processing power, yet preserved small-world architecture in comparison with rest. These findings demonstrate that the default mode network does not disengage during this paradigm, but instead may be involved in task relevant processing.The Evelyn Trust (RUAG/018) provided the required funding for this research. Additionally, D Vatansever is funded by the Yousef Jameel Academic Program administered via the Cambridge Commonwealth, European and International Trust; DK Menon is supported by funding from the NIHR Cambridge Biomedical Centre (RCZB/004), and an NIHRSenior Investigator Award (RCZB/014), and EA Stamatakis is funded by the Stephen Erskine Fellowship Queens' College Cambridge. We would also like to thank Sanja Abbott for programming the stimulus delivery, Dr. Guy Williams and Victoria Lupson and the rest of the staff in the Wolfson Brain Imaging Centre (WBIC) at Addenbrooke's Hospital for their assistance in scanning. Last but not least, we thank all the participants for their contribution to this study.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.neuroimage.2015.07.05

Default Mode Contributions to Automated Information Processing

Concurrent with mental processes that require rigorous computation and control, a series of automated decisions and actions govern our daily lives, providing efficient and adaptive responses to environmental demands. Using a cognitive flexibility task, we show that a set of brain regions collectively known as the default mode network play a crucial role in such “autopilot” behavior, i.e. when rapidly selecting appropriate responses under predictable behavioral contexts. While applying learned rules, the default mode network shows both greater activity and connectivity. Furthermore, functional interactions between this network and hippocampal, parahippocampal areas as well as primary visual cortex correlate with the speed of accurate responses. These findings indicate a memory-based “autopilot role” for the default mode network, which may have important implications for our current understanding of healthy and adaptive brain processing.We thank Mrs. Victoria Lupson, Ms. Karen Welsh, Dr. Marius Mada, and the rest of the staff in the Wolfson Brain Imaging Centre (WBIC) at Addenbrooke’s Hospital for their assistance in MRI scanning. In addition, we thank all the participants for their contribution to this study. This study was funded by the Yousef Jameel Academic Program grant (awarded to D.V.). Additionally, D.K.M. is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Centre (RCZB/004) and an NIHR Senior Investigator Award (RCZB/014), and E.A.S. is funded by the Stephen Erskine Fellowship Queens’ College, Cambridge

Controlling a spillover pathway with the molecular cork effect

Spillover of reactants from one active site to another is important in heterogeneous catalysis and has recently been shown to enhance hydrogen storage in a variety of materials. The spillover of hydrogen is notoriously hard to detect or control. We report herein that the hydrogen spillover pathway on a Pd/Cu alloy can be controlled by reversible adsorption of a spectator molecule. Pd atoms in the Cu surface serve as hydrogen dissociation sites from which H atoms can spillover onto surrounding Cu regions. Selective adsorption of CO at these atomic Pd sites is shown to either prevent the uptake of hydrogen on, or inhibit its desorption from, the surface. In this way, the hydrogen coverage on the whole surface can be controlled by molecular adsorption at a minority site, which we term a ‘molecular cork’ effect. We show that the molecular cork effect is present during a surface catalysed hydrogenation reaction and illustrate how it can be used as a method for controlling uptake and release of hydrogen in a model storage system

Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate

Traumatic brain injury (TBI) often results in cognitive impairments for patients. The aim of this proof of concept study was to establish the nature of abnormalities, in terms of activity and connectivity, in the working memory network of TBI patients and how these relate to compromised behavioral outcomes. Further, this study examined the neural correlates of working memory improvement following the administration of methylphenidate. We report behavioral, functional and structural MRI data from a group of 15 Healthy Controls (HC) and a group of 15 TBI patients, acquired during the execution of the N-back task. The patients were studied on two occasions after the administration of either placebo or 30 mg of methylphenidate. Between group tests revealed a significant difference in performance when HCs were compared to TBI patients on placebo [F$_{(1, 28)}$ = 4.426, p < 0.05, η$_{p}$$^{2}$ = 0.136]. This difference disappeared when the patients took methylphenidate [F$_{(1, 28)}$ = 3.665, p = 0.66]. Patients in the middle range of baseline performance demonstrated the most benefit from methylphenidate. Changes in the TBI patient activation levels in the Left Cerebellum significantly and positively correlated with changes in performance (r = 0.509, df = 13, p = 0.05). Whole-brain connectivity analysis using the Left Cerebellum as a seed revealed widespread negative interactions between the Left Cerebellum and parietal and frontal cortices as well as subcortical areas. Neither the TBI group on methylphenidate nor the HC group demonstrated any significant negative interactions. Our findings indicate that (a) TBI significantly reduces the levels of activation and connectivity strength between key areas of the working memory network and (b) Methylphenidate improves the cognitive outcomes on a working memory task. Therefore, we conclude that methylphenidate may render the working memory network in a TBI group more consistent with that of an intact working memory network.This work was supported by the Evelyn Trust (grant number 06/20). The Evelyn Trust had no role in the conduct of the research for the preparation of the manuscript. DM is supported by the Neuroscience Theme of the NIHR Cambridge Biomedical Research Centre and NIHR Senior Investigator awards, and by Framework Program 7 funding from the European Commission (TBIcare). ES is funded by the Stephen Erskine Fellowship, Queens' College, University of Cambridge, UK

Sensory cortical response to uncertainty and low salience during recognition of affective cues in musical intervals

Previous neuroimaging studies have shown an increased sensory cortical response (i.e., heightened weight on sensory evidence) under higher levels of predictive uncertainty. The signal enhancement theory proposes that attention improves the quality of the stimulus representation, and therefore reduces uncertainty by increasing the gain of the sensory signal. The present study employed functional magnetic resonance imaging (fMRI) to investigate the neural correlates for ambiguous valence inferences signaled by auditory information within an emotion recognition paradigm. Participants categorized sound stimuli of three distinct levels of consonance/dissonance controlled by interval content. Separate behavioural and neuroscientific experiments were conducted. Behavioural results revealed that, compared with the consonance condition (perfect fourths, fifths and octaves) and the strong dissonance condition (minor/major seconds and tritones), the intermediate dissonance condition (minor thirds) was the most ambiguous, least salient and more cognitively demanding category (slowest reaction times). The neuroscientific findings were consistent with a heightened weight on sensory evidence whilst participants were evaluating intermediate dissonances, which was reflected in an increased neural response of the right Heschl's gyrus. The results support previous studies that have observed enhanced precision of sensory evidence whilst participants attempted to represent and respond to higher degrees of uncertainty, and converge with evidence showing preferential processing of complex spectral information in the right primary auditory cortex. These findings are discussed with respect to music-theoretical concepts and recent Bayesian models of perception, which have proposed that attention may heighten the weight of information coming from sensory channels to stimulate learning about unknown predictive relationships.This project was made possible through the support of a Queens’ College Cambridge Walker Studentship to F. Bravo. Financial support has also been provided by: Zukunftskonzept at TU Dresden (Exzellenzinitiative of the Deutsche Forschungsgemeinschaft), SEMPRE (Arnold Bentley New Initiatives Fund), and Cambridge Society for the Application of Research through a CSAR Student Award to F. Bravo

Bayesian Inference of Task-Based Functional Brain Connectivity Using Markov Chain Monte Carlo Methods

The study of functional networks in the brain is essential in order to gain a better insight into its diverse set of operations and to characterise the associated normal and abnormal behaviours. Present methods of analysing fMRI data to obtain functional connectivity are largely limited to approaches such as correlation, regression and independent component analysis, which give simple point estimates. By contrast, we propose a stochastic linear model in a Bayesian setting and employ Markov Chain Monte Carlo methods to approximate posterior distributions of full connectivity and covariance matrices. Through the use of a Bayesian probabilistic framework, distributional estimates of the linkage strengths are obtained as opposed to point estimates, and the uncertainty of the existence of such links is accounted for. We decompose the connectivity matrix as the Hadamard product of binary indicators and real-valued variables, and formulate an efficient joint-sampling scheme to infer them. The well-characterised somato-motor network is examined in a self-paced, right-handed finger opposition task based experiment, while nodes from the visual network are used for contrast during the same experiment. Unlike for the visual network, significant changes in connectivity are found in the motor network during the task. Our work provides a distributional metric for functional connectivity along with causality information, and contributes to the collection of network level descriptors of brain functions.Engineering and Physical Sciences Research Council Grant ID: EP/K020153/1; Yousef Jameel Scholarship Programm

Angular Default Mode Network Connectivity across Working Memory Load

Initially identified during no-task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large-scale brain networks. Nevertheless, its contribution to whole-brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI-based $n$-back paradigm with parametric increases in difficulty. Using a voxel-wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of $n$-back task load. Subsequent seed-based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large-scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n-back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands.Evelyn Trust (RUAG/018), Yousef Jameel Academic Program, National Institute for Health Research Cambridge Biomedical Centre (RCZB/004), National Institute for Health Research (Senior Investigator Award (RCZB/014)), Queens’ College Cambridge (Stephen Erskine Fellowship

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels.Studies were conducted at the NIHR Wellcome trust clinical research facility. L.M.L. was funded by a Post-Doctoral Fellowship from the University of Granada. E.A.S. is funded by the Stephen Erskine Fellowship, Queens' College, Cambridge

Simonsenia aveniformis sp nov (Bacillariophyceae), molecular phylogeny and systematics of the genus, and a new type of canal raphe system

The genus Simonsenia is reviewed and S. aveniformis described as new for science by light and electron microscopy. The new species originated from estuarine environments in southern Iberia (Atlantic coast) and was isolated into culture. In LM, Simonsenia resembles Nitzschia, with bridges (fibulae) beneath the raphe, which is marginal. It is only electron microscope (EM) examination that reveals the true structure of the raphe system, which consists of a raphe canal raised on a keel (wing), supported by rib like braces (fenestral bars) and tube-like portulae; between the portulae the keel is perforated by open windows (fenestrae). Based on the presence of portulae and a fenestrated keel, Simonsenia has been proposed to be intermediate between Bacillariaceae and Surirellaceae. However, an rbcL phylogeny revealed that Simonsenia belongs firmly in the Bacillariaceae, with which it shares a similar chloroplast arrangement, rather than in the Surirellaceae. Lack of homology between the surirelloid and simonsenioid keels is reflected in subtle differences in the morphology and ontogeny of the portulae and fenestrae. The diversity of Simonsenia has probably been underestimated, particularly in the marine environment.Polish National Science Centre in Cracow within the Maestro program [N 2012/04/A/ST10/00544]; Sciences and Technologies Foundation-FCT (Portugal) [SFRH/BD/62405/2009]info:eu-repo/semantics/publishedVersio