bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of the Human Structural Connectome Underlying Working Memory Training
Authors: Caeyenberghs Karen , Metzler-Baddeley Claudia , Foley Sonya , Jones Derek K. 
Published: April 2016

Brain region-specific changes have been demonstrated with a variety of cognitive training interventions. The effect of cognitive training on brain subnetworks in humans, however, remains largely unknown, with studies limited to functional networks. Here, we used a well-established working memory training program and state-of-the art neuroimaging methods in 40 healthy adults (21 females, mean age 26.5 years). Near and far-transfer training effects were assessed using computerized working memory and executive function tasks. Adaptive working memory training led to improvement on (non)trained working memory tasks and generalization to tasks of reasoning and inhibition. Graph theoretical analysis of the structural (white matter) network connectivity (“connectome”) revealed increased global integration within a frontoparietal attention network following adaptive working memory training compared with the nonadaptive group. Furthermore, the impact on the outcome of graph theoretical analyses of different white matter metrics to infer “connection strength” was evaluated. Increased efficiency of the frontoparietal network was best captured when using connection strengths derived from MR metrics that are thought to be more sensitive to differences in myelination (putatively indexed by the [quantitative] longitudinal relaxation rate, R1) than previously used diffusion MRI metrics (fractional anisotropy or fiber-tracking recovered streamlines). Our findings emphasize the critical role of specific microstructural markers in providing important hints toward the mechanisms underpinning training-induced plasticity that may drive working memory improvement in clinical populations.SIGNIFICANCE STATEMENTThis is the first study to explore training-induced changes in the structural connectome using a well-controlled design to examine cognitive training with up-to-date neuroimaging methods. We found changes in global integration based on white matter connectivity within a frontoparietal attention network following adaptive working memory training compared with a nonadaptive comparison group. Furthermore, the impact of different diffusion MR metrics and more specific markers of white matter on the graph theoretical findings was evaluated. An increase in network global efficiency following working memory training was best captured when connection strengths were weighted by MR relaxation rates (influenced by myelination). These results are important for the optimization of cognitive training programs for healthy individuals and people with brain disease.
Inferring Cortical Variability from Local Field Potentials
Authors: Cui Yuwei , Liu Liu D. , McFarland James M. , Pack Christopher C. , Butts Daniel A. 
Published: April 2016

The responses of sensory neurons can be quite different to repeated presentations of the same stimulus. Here, we demonstrate a direct link between the trial-to-trial variability of cortical neuron responses and network activity that is reflected in local field potentials (LFPs). Spikes and LFPs were recorded with a multielectrode array from the middle temporal (MT) area of the visual cortex of macaques during the presentation of continuous optic flow stimuli. A maximum likelihood-based modeling framework was used to predict single-neuron spiking responses using the stimulus, the LFPs, and the activity of other recorded neurons. MT neuron responses were strongly linked to gamma oscillations (maximum at 40 Hz) as well as to lower-frequency delta oscillations (1–4 Hz), with consistent phase preferences across neurons. The predicted modulation associated with the LFP was largely complementary to that driven by visual stimulation, as well as the activity of other neurons, and accounted for nearly half of the trial-to-trial variability in the spiking responses. Moreover, the LFP model predictions accurately captured the temporal structure of noise correlations between pairs of simultaneously recorded neurons, and explained the variation in correlation magnitudes observed across the population. These results therefore identify signatures of network activity related to the variability of cortical neuron responses, and suggest their central role in sensory cortical function.SIGNIFICANCE STATEMENTThe function of sensory neurons is nearly always cast in terms of representing sensory stimuli. However, recordings from visual cortex in awake animals show that a large fraction of neural activity is not predictable from the stimulus. We show that this variability is predictable given the simultaneously recorded measures of network activity, local field potentials. A model that combines elements of these signals with the stimulus processing of the neuron can predict neural responses dramatically better than current models, and can predict the structure of correlations across the cortical population. In identifying ways to understand stimulus processing in the context of ongoing network activity, this work thus provides a foundation to understand the role of sensory cortex in combining sensory and cognitive variables.
Brain Signal Variability Differentially Affects Cognitive Flexibility and Cognitive Stability
Authors: Armbruster-Genç Diana J. N. , Ueltzhöffer Kai , Fiebach Christian J. 
Published: April 2016

Recent research yielded the intriguing conclusion that, in healthy adults, higher levels of variability in neuronal processes are beneficial for cognitive functioning. Beneficial effects of variability in neuronal processing can also be inferred from neurocomputational theories of working memory, albeit this holds only for tasks requiring cognitive flexibility. However, cognitive stability, i.e., the ability to maintain a task goal in the face of irrelevant distractors, should suffer under high levels of brain signal variability. To directly test this prediction, we studied both behavioral and brain signal variability during cognitive flexibility (i.e., task switching) and cognitive stability (i.e., distractor inhibition) in a sample of healthy human subjects and developed an efficient and easy-to-implement analysis approach to assess BOLD-signal variability in event-related fMRI task paradigms. Results show a general positive effect of neural variability on task performance as assessed by accuracy measures. However, higher levels of BOLD-signal variability in the left inferior frontal junction area result in reduced error rate costs during task switching and thus facilitate cognitive flexibility. In contrast, variability in the same area has a detrimental effect on cognitive stability, as shown in a negative effect of variability on response time costs during distractor inhibition. This pattern was mirrored at the behavioral level, with higher behavioral variability predicting better task switching but worse distractor inhibition performance. Our data extend previous results on brain signal variability by showing a differential effect of brain signal variability that depends on task context, in line with predictions from computational theories.SIGNIFICANCE STATEMENTRecent neuroscientific research showed that the human brain signal is intrinsically variable and suggested that this variability improves performance. Computational models of prefrontal neural networks predict differential effects of variability for different behavioral situations requiring either cognitive flexibility or stability. However, this hypothesis has so far not been put to an empirical test. In this study, we assessed cognitive flexibility and cognitive stability, and, besides a generally positive effect of neural variability on accuracy measures, we show that neural variability in a prefrontal brain area at the inferior frontal junction is differentially associated with performance: higher levels of variability are beneficial for the effectiveness of task switching (cognitive flexibility) but detrimental for the efficiency of distractor inhibition (cognitive stability).
BAZ1B in Nucleus Accumbens Regulates Reward-Related Behaviors in Response to Distinct Emotional Stimuli
Authors: Sun HaoSheng , Martin Jennifer A. , Werner Craig T. , Wang Zi-Jun , Damez-Werno Diane M. , Scobie Kimberly N. , Shao Ning-Yi , Dias Caroline , Rabkin Jacqui , Koo Ja Wook , Gancarz Amy M. , Mouzon Ezekiell A. , Neve Rachael L. , Shen Li , Dietz David M. , Nestler Eric J. 
Published: April 2016

ATP-dependent chromatin remodeling proteins are being implicated increasingly in the regulation of complex behaviors, including models of several psychiatric disorders. Here, we demonstrate thatBaz1b, an accessory subunit of the ISWI family of chromatin remodeling complexes, is upregulated in the nucleus accumbens (NAc), a key brain reward region, in both chronic cocaine-treated mice and mice that are resilient to chronic social defeat stress. In contrast, no regulation is seen in mice that are susceptible to this chronic stress. Viral-mediated overexpression ofBaz1b, along with its associated subunitSmarca5, in mouse NAc is sufficient to potentiate both rewarding responses to cocaine, including cocaine self-administration, and resilience to chronic social defeat stress. However, despite these similar, proreward behavioral effects, genome-wide mapping of BAZ1B in NAc revealed mostly distinct subsets of genes regulated by these chromatin remodeling proteins after chronic exposure to either cocaine or social stress. Together, these findings suggest important roles for BAZ1B and its associated chromatin remodeling complexes in NAc in the regulation of reward behaviors to distinct emotional stimuli and highlight the stimulus-specific nature of the actions of these regulatory proteins.SIGNIFICANCE STATEMENTWe show that BAZ1B, a component of chromatin remodeling complexes, in the nucleus accumbens regulates reward-related behaviors in response to chronic exposure to both rewarding and aversive stimuli by regulating largely distinct subsets of genes.
Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)
Authors: Blackman Rachael K. , Crowe David A. , DeNicola Adele L. , Sakellaridi Sofia , MacDonald Angus W. , Chafee Matthew V. 
Published: April 2016

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia.SIGNIFICANCE STATEMENTFunctional imaging studies have demonstrated that cognitive control deficits in schizophrenia are associated with reduced activation of the dorsolateral prefrontal cortex (MacDonald et al., 2005). However, these data do not reveal how the disease has disrupted the function of prefrontal neurons to produce the observed deficits in cognitive control. Relating cognitive control to neurophysiological signals at a cellular level in prefrontal cortex is a necessary first step toward understanding how disruption of these signals could lead to cognitive control failure in neuropsychiatric disease. To that end, we translated a task that measures cognitive control deficits in patients with schizophrenia to monkeys and describe here how neural signals in prefrontal cortex relate to performance.
Compensatory Neural Activity in Response to Cognitive Fatigue
Authors: Wang Chao , Trongnetrpunya Amy , Samuel Immanuel Babu Henry , Ding Mingzhou , Kluger Benzi M. 
Published: April 2016

Prolonged continuous performance of a cognitively demanding task induces cognitive fatigue and is associated with a time-related deterioration of objective performance, the degree of which is referred to cognitive fatigability. Although the neural underpinnings of cognitive fatigue are poorly understood, prior studies report changes in neural activity consistent with deterioration of task-related networks over time. While compensatory brain activity is reported to maintain motor task performance in the face of motor fatigue and cognitive performance in the face of other stressors (e.g., aging) and structural changes, there are no studies to date demonstrating compensatory activity for cognitive fatigue. High-density electroencephalography was recorded from human subjects during a 160 min continuous performance of a cognitive control task. While most time-varying neural activity showed a linear decline over time, we identified an evoked potential over the anterior frontal region which demonstrated an inverted U-shaped time-on-task profile. This evoked brain activity peaked between 60 and 100 min into the task and was positively associated with better behavioral performance only during this interval. Following the peak and during subsequent decline of this anterior frontal activity, the rate of performance decline also accelerated. These findings demonstrate that this anterior frontal brain activity, which is not part of the primary task-related activity at baseline, is recruited to compensate for fatigue-induced impairments in the primary task-related network, and that this compensation terminates as cognitive fatigue further progresses. These findings may be relevant to understanding individual differences in cognitive fatigability and developing interventions for clinical conditions afflicted by fatigue.SIGNIFICANCE STATEMENTFatigue refers to changes in objective performance and subjective effort induced by continuous task performance. We examined the neural underpinnings of cognitive fatigue in humans using a prolonged continuous performance task and high-density electroencephalography with the goal of determining whether compensatory processes exist to maintain performance in the face of fatigue. We identified brain activity demonstrating an inverted U-shaped time-on-task profile. This brain activity showed features consistent with a compensatory role including: peaking between 60 and 100 min into the task, a positive association with behavioral performance only during this interval, and accelerated performance decline following its peak. These findings may be relevant to understanding individual differences in cognitive fatigue and developing interventions for clinical conditions afflicted by fatigue.
Brain-Wide Maps of Synaptic Input to Cortical Interneurons
Authors: Wall Nicholas R. , De La Parra Mauricio , Sorokin Jordan M. , Taniguchi Hiroki , Huang Z. Josh , Callaway Edward M. 
Published: April 2016

Cortical inhibition is mediated by diverse inhibitory neuron types that can each play distinct roles in information processing by virtue of differences in their input sources, intrinsic properties, and innervation targets. Previous studies in brain slices have demonstrated considerable cell-type specificity in laminar sources of local inputs. In contrast, little is known about possible differences in distant inputs to different cortical interneuron types. We used the monosynaptic rabies virus system, in conjunction with mice expressing Cre recombinase in either parvalbumin-positive, somatostatin-positive (SST+), or vasoactive intestinal peptide-positive (VIP+) neurons, to map the brain-wide input to the three major nonoverlapping classes of interneurons in mouse somatosensory cortex. We discovered that all three classes of interneurons received considerable input from known cortical and thalamic input sources, as well as from probable cholinergic cells in the basal nucleus of Meynert. Despite their common input sources, these classes differed in the proportion of long-distance cortical inputs originating from deep versus superficial layers. Similar to their laminar differences in local input, VIP+ neurons received inputs predominantly from deep layers while SST+ neurons received mostly superficial inputs. These classes also differed in the amount of input they received. Cortical and thalamic inputs were greatest onto VIP+ interneurons and smallest onto SST+ neurons.SIGNIFICANCE STATEMENTThese results indicate that all three major interneuron classes in the barrel cortex integrate both feedforward and feedback information from throughout the brain to modulate the activity of the local cortical circuit. However, differences in laminar sources and magnitude of distant cortical input suggest differential contributions from cortical areas. More input to vasoactive intestinal peptide-positive (VIP+) neurons than to somatostatin-positive (SST+) neurons suggests that disinhibition of the cortex via VIP+ cells, which inhibit SST+ cells, might be a general feature of long-distance corticocortical and thalamocortical circuits.
Promotion of Functional Nerve Regeneration by Inhibition of Microtubule Detyrosination
Authors: Gobrecht Philipp , Andreadaki Anastasia , Diekmann Heike , Heskamp Annemarie , Leibinger Marco , Fischer Dietmar 
Published: April 2016

Functional recovery of injured peripheral neurons often remains incomplete, but the clinical outcome can be improved by increasing the axonal growth rate. Adult transgenic GSK3αS/A/βS/Aknock-in mice with sustained GSK3 activity show markedly accelerated sciatic nerve regeneration. Here, we unraveled the molecular mechanism underlying this phenomenon, which led to a novel pharmacological approach for the promotion of functional recovery after nerve injury.In vitroandin vivoanalysis of GSK3 single knock-in mice revealed the unexpected contribution of GSK3α in addition to GSK3β, as both GSK3S/Aknock-ins improved axon regeneration. Moreover, growth stimulation depended on overall GSK3 activity, correlating with increased phosphorylation of microtubule-associated protein 1B and reduced microtubule detyrosination in axonal tips. Pharmacological inhibition of detyrosination by parthenolide or cnicin mimicked this axon growth promotion in wild-type animals, although it had no effect in GSK3αS/A/βS/Amice. These results support the conclusion that sustained GSK3 activity primarily targets microtubules in growing axons, maintaining them in a more dynamic state to facilitate growth. Accordingly, further manipulation of microtubule stability using either paclitaxel or nocodazole compromised the effects of parthenolide. Strikingly, either local or systemic application of parthenolide in wild-type mice dose-dependently acceleratedin vivoaxon regeneration and functional recovery similar to GSK3αS/A/βS/Amice. Thus, reducing microtubule detyrosination in axonal tips may be a novel, clinically suitable strategy to treat nerve damage.SIGNIFICANCE STATEMENTPeripheral nerve regeneration often remains incomplete, due to an insufficient growth rate of injured axons. Transgenic mice with sustained GSK3 activity showed markedly accelerated nerve regeneration upon injury. Here, we identified the molecular mechanism underlying this phenomenon and provide a novel therapeutic principle for promoting nerve repair. Analysis of transgenic mice revealed a dependence on overall GSK3 activity and reduction of microtubule detyrosination in axonal tips. Pharmacological inhibition of detyrosination by parthenolide fully mimicked this axon growth promotion in wild-type mice. Strikingly, local or systemic treatment with parthenolidein vivomarkedly accelerated axon regeneration and functional recovery. Thus, pharmacological inhibition of microtubule detyrosination may be a novel, clinically suitable strategy for nerve repair with potential relevance for human patients.
Constituting community through food charters: A rhetorical-genre analysis
Authors: Spoel Philippa , Derkatch Colleen 
Published: April 2016

Communities across Canada are increasingly developing food charters, with at least 22 regional charters published in Ontario alone. As a rhetorical genre, food charters are persuasive actions that articulate not only the kind of food system to which a community aspires, but also the kind of community that it aspires to be. We argue that Ontario’s food charters play an important role in constituting a sense of community identity and values through the rhetorical action of the genre itself. We analyze how this is accomplished through two rhetorical features, the naming of community and the listing of community priorities, showing how these features simultaneously obscure and reveal ideological tensions and logical incongruities within each community’s vision for its food system. Our analysis illustrates how the genre of the food charter both responds to and shapes the diverse, possibly conflicting values that inform food policy and food security initiatives in Ontario, and it offers insight into how the genre itself may inadvertently constrain the action it is intended to perform.
The Politics of Mythmaking: Foreign Policy in Canadian Federal Elections 1958-1965
Authors: Kinsinger Kristopher 
Published: April 2016

<span style="font-family: Calibri, sans-serif;">The notion of a Canadian foreign policy “golden age” during the decades following the Second World War has shaped how Canadians have come to view their country’s place in the world. While recent historical scholarship has laudably done much to demonstrate how the idea of a Canadian diplomatic “golden age” is ultimately an exercise in mythmaking, historians have done comparatively little to assess when and how this mythological notion became ingrained in Canada’s political consciousness. This paper seeks to begin to fill this gap in the historiography of Canadian politics by analyzing the role of foreign policy in the four federal elections held between 1958 and 1965. This analysis not only reaffirms the mythological status of the “golden age” but also demonstrates how this notion was fuelled by the foreign policy rhetoric of the Liberal Party during Lester B. Pearson’s tenure as leader. </span>