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Journal articleGoldstone AP, 2015,
Changes in Reward after Gastric Bypass: the Advantages and Disadvantages
, Current Atherosclerosis Reports, Vol: 17, ISSN: 1534-6242Gastric bypass surgery is an effective long-term weight loss intervention. Key to its success appears a putative shift in food preference away from high-energy-density foods associated with a reduced appetitive drive and loss of neural reactivity in the reward system of the brain towards food. Post-prandial exaggerated satiety gut hormone responses have been implicated as mediators. Whilst the positive impact of bariatric surgery on both physical and psychological outcomes for many patients is clearly evident, a subset of patients appear to be detrimentally affected by this loss of reward from food and by a lack of alternative strategies for regulating affect after surgery. Mindfulness training has emerged as a potential tool in reducing the need for immediate reward that underpins much of eating behaviour. Further research is needed to help identify patients who may be more vulnerable after gastric bypass and which forms of support may be most beneficial.
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Journal articleHampshire A, Sharp DJ, 2015,
Contrasting network and modular perspectives on inhibitory control.
, Trends in Cognitive Sciences, ISSN: 1364-6613A prominent theory proposes that the right inferior frontal cortex of the human brain houses a dedicated region for motor response inhibition. However, there is growing evidence to support the view that this inhibitory control hypothesis is incorrect. Here, we discuss evidence in favour of our alternative hypothesis, which states that response inhibition is one example of a broader class of control processes that are supported by the same set of frontoparietal networks. These domain-general networks exert control by modulating local lateral inhibition processes, which occur ubiquitously throughout the cortex. We propose that to fully understand the neural basis of behavioural control requires a more holistic approach that considers how common network mechanisms support diverse cognitive processes.
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Journal articleAlsters SIM, Goldstone AP, Buxton JL, et al., 2015,
Truncating homozygous mutation of carboxypeptidase E (CPE) in a morbidly obese female with type 2 diabetes mellitus, intellectual disability and hypogonadotrophic hypogonadism
, PLOS One, Vol: 10, ISSN: 1932-6203Carboxypeptidase E is a peptide processing enzyme, involved in cleaving numerous peptide precursors, including neuropeptides and hormones involved in appetite control and glucose metabolism. Exome sequencing of a morbidly obese female from a consanguineous family revealed homozygosity for a truncating mutation of the CPE gene (c.76_98del; p.E26RfsX68). Analysis detected no CPE expression in whole blood-derived RNA from the proband, consistent with nonsense-mediated decay. The morbid obesity, intellectual disability, abnormal glucose homeostasis and hypogonadotrophic hypogonadism seen in this individual recapitulates phenotypes in the previously described fat/fat and Cpe knockout mouse models, evidencing the importance of this peptide/hormone-processing enzyme in regulating body weight, metabolism, and brain and reproductive function in humans.
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Journal articleShanahan MP, Hellyer P, Sharp DJ, et al., 2015,
Cognitive flexibility through metastable neural dynamics is disrupted by damage to the structural connectome
, Journal of Neuroscience, Vol: 35, Pages: 9050-9063, ISSN: 0270-6474Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome.
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Journal articleVáša F, Shanahan M, Hellyer P, et al., 2015,
Effects of lesions on synchrony and metastability in cortical networks
, Neuroimage, Vol: 118, Pages: 456-467, ISSN: 1095-9572At the macroscopic scale, the human brain can be described as a complex network of white matter tracts integrating grey matter assemblies — the human connectome. The structure of the connectome, which is often described using graph theoretic approaches, can be used to model macroscopic brain function at low computational cost. Here, we use the Kuramoto model of coupled oscillators with time-delays, calibrated with respect to empirical functional MRI data, to study the relation between the structure of the connectome and two aspects of functional brain dynamics — synchrony, a measure of general coherence, and metastability, a measure of dynamical flexibility. Specifically, we investigate the relationship between the local structure of the connectome, quantified using graph theory, and the synchrony and metastability of the model's dynamics. By removing individual nodes and all of their connections from the model, we study the effect of lesions on both global and local dynamics. Of the nine nodal graph-theoretical properties tested, two were able to predict effects of node lesion on the global dynamics. The removal of nodes with high eigenvector centrality leads to decreases in global synchrony and increases in global metastability, as does the removal of hub nodes joining topologically segregated network modules. At the level of local dynamics in the neighbourhood of the lesioned node, structural properties of the lesioned nodes hold more predictive power, as five nodal graph theoretical measures are related to changes in local dynamics following node lesions. We discuss these results in the context of empirical studies of stroke and functional brain dynamics.
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Journal articleSharp DJ, Jenkins PO, 2015,
Concussion is confusing us all.
, Practical Neurology, Vol: 15, Pages: 172-186, ISSN: 1474-7766It is time to stop using the term concussion as it has no clear definition and no pathological meaning. This confusion is increasingly problematic as the management of 'concussed' individuals is a pressing concern. Historically, it has been used to describe patients briefly disabled following a head injury, with the assumption that this was due to a transient disorder of brain function without long-term sequelae. However, the symptoms of concussion are highly variable in duration, and can persist for many years with no reliable early predictors of outcome. Using vague terminology for post-traumatic problems leads to misconceptions and biases in the diagnostic process, producing uninterpretable science, poor clinical guidelines and confused policy. We propose that the term concussion should be avoided. Instead neurologists and other healthcare professionals should classify the severity of traumatic brain injury and then attempt to precisely diagnose the underlying cause of post-traumatic symptoms.
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Journal articleParkin BL, Hellyer PJ, Leech R, et al., 2015,
Dynamic network mechanisms of relational integration
, Journal of Neuroscience, Vol: 35, Pages: 7660-7673, ISSN: 1529-2401© 2015 Parkin et al. A prominent hypothesis states that specialized neural modules within the human lateral frontopolar cortices (LFPCs) support “relational integration” (RI), the solving of complex problems using inter-related rules. However, it has been proposed that LFPC activity during RI could reflect the recruitment of additional “domain-general” resources when processing more difficult problems in general as opposed to RI specifically. Moreover, theoretical research with computational models has demonstrated that RI may be supported by dynamic processes that occur throughout distributed networks of brain regions as opposed to within a discrete computational module. Here, we present fMRI findings from a novel deductive reasoning paradigm that controls for general difficulty while manipulating RI demands. In accordance with the domaingeneral perspective, we observe an increase in frontoparietal activation during challenging problems in general as opposed to RI specifically. Nonetheless, when examining frontoparietal activity using analyses of phase synchrony and psychophysiological interactions, we observe increased network connectivity during RI alone. Moreover, dynamic causal modeling with Bayesian model selection identifies the LFPC as the effective connectivity source. Based on these results, we propose that during RI an increase in network connectivity and a decrease in network metastability allows rules that are coded throughout working memory systems to be dynamically bound. This change in connectivity state is top-down propagated via a hierarchical system of domain-general networks with the LFPC at the apex. In this manner, the functional network perspective reconciles key propositions of the globalist, modular, and computational accounts of RI within a single unified framework.
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Journal articleLi LM, Uehara K, Hanakawa T, 2015,
The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies
, Frontiers in Cellular Neuroscience, Vol: 9, ISSN: 1662-5102There has been an explosion of research using transcranial direct current stimulation (tDCS) for investigating and modulating human cognitive and motor function in healthy populations. It has also been used in many studies seeking to improve deficits in disease populations. With the slew of studies reporting “promising results” for everything from motor recovery after stroke to boosting memory function, one could be easily seduced by the idea of tDCS being the next panacea for all neurological ills. However, huge variability exists in the reported effects of tDCS, with great variability in the effect sizes and even contradictory results reported. In this review, we consider the interindividual factors that may contribute to this variability. In particular, we discuss the importance of baseline neuronal state and features, anatomy, age and the inherent variability in the injured brain. We additionally consider how interindividual variability affects the results of motor-evoked potential (MEP) testing with transcranial magnetic stimulation (TMS), which, in turn, can lead to apparent variability in response to tDCS in motor studies.
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Conference paperWhittington A, Iturria-Medina Y, Evans A, et al., 2015,
A network-spreading model to characterize the accumulation of beta-amyloid in Alzheimer's Disease
, Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505 -
Journal articleKirschner A, Cruse D, Chennu S, et al., 2015,
A P300-based cognitive assessment battery
, Brain and Behavior, Vol: 5, ISSN: 2162-3279Background: It is well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are capable of higher cognitive processes. Methods: Here, we develop a series of EEG paradigms that probe several core aspects of cognition at the bedside without the need for motor responses and explore the sensitivity of this approach in a group of healthy controls. Results: Using analysis of ERPs alone, this method can determine with high reliability whether individual participants are able to attend a stimulus stream, maintain items in working memory, or solve complex grammatical reasoning problems. Conclusion: We suggest that this approach could form the basis of a brain-based battery for assessing higher cognition in patients with severe motor impairments or disorders of consciousness.
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