Towards a cognitive neurobiology of brain-gut axis disorders

The past two decades have seen substantial gains in our understanding of the complex processes underlying disturbed brain-gut communication in disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Despite a growing understanding of the neurobiology of brain-gut axis dysfunction, there is a relative paucity of investigations into how the various factors involved in dysregulating the brain-gut axis, including stress, immune activation and pain, could impact on fundamental brain processes such as cognitive performance. To this end, we proposed a cognitive neurobiology of brain-gut axis dysfunction and took a novel approach to examine how disturbed brain-gut interactions may manifest as altered cognitive performance in IBS and IBD, both cross-sectionally and prospectively. We have demonstrated that, disorders of the brain-gut axis are characterised by stable deficits in specific cognitive domains. Specifically, patients with IBS exhibit a consistent hippocampal mediated visuospatial memory impairment. In addition we have found evidence to suggest a similar visuospatial impairment in IBD. However, our most consistent finding within this population was that patients with Crohn’s disease exhibit impaired selective attention/ response inhibition on the classic Stroop interference test. These cognitive deficits may serve to perpetuate and sustain brain-gut axis dysfunction. Furthermore, this research has shed light on some of the underlying neurobiological mechanisms that may be mediating cognitive dysfunction in IBS. Our findings may have significant implications for the individual who suffers from a brain-gut axis disorder and may also inform future treatment strategies. Taken together, these findings can be incorporated into existing neurobiological models of brain-gut axis dysfunction, to develop a more comprehensive model accounting for the cognitive-neurobiology of brain-gut axis disorders. This has furthered our understanding of disease pathophysiology and may ultimately aid in both the diagnosis and treatment of these highly prevalent, but poorly understood disorders.

Evaluation of rhizobacterial colonisation and the ability to induce Globodera pallida hatch

Three bacterial isolates, SB13 (Acinetobacter sp.), SB14 (Arthrobacter sp.) and SB15 (Bacillus sp.), were previously isolated from the rhizosphere of sugar beet (Beta vulgaris ssp. vulgaris) plants and shown to increase hatch of potato cyst nematodes in vitro. In this study, the three isolates were assayed for rhizosphere competence. Each isolate was applied to seeds at each of four concentrations (105-108 CFU ml−1) and the inoculated seeds were planted in plastic microcosms containing coarse sand. All three isolates were shown to colonise the rhizosphere, although to differing degrees, with the higher inoculation densities providing significantly better colonisation. The isolates increased sugar beet root and shoot dry weight. Isolates SB14 and SB15 were analysed for their ability to induce in vivo hatch of Globodera pallida in non-sterile soil planted with sugar beet. After 4 and 6 weeks, both isolates had induced significantly greater percentage hatch compared to controls.

The Quick Mild Cognitive Impairment (Qmci) screen: developing a new screening test for mild cognitive impairment and dementia

Introduction: Identifying mild cognitive impairment (MCI) is challenging. Few short instruments have sufficient sensitivity and specificity for use in busy clinical practice. This thesis explores the development, psychometric evaluation and validation of a new short (3–5 min) cognitive screening instrument, designed to screen for MCI and early dementia, called the Quick Mild Cognitive Impairment (Q

Optimal assessment of the ability of children with recurrent respiratory tract infections to produce anti-polysaccharide antibodies.

Specific anti-polysaccharide antibody deficiency (SPAD) is an immune disorder. Diagnostic criteria have not yet been defined clearly. One hundred and seventy-six children evaluated for recurrent respiratory tract infections were analysed retrospectively. For each subject, specific anti-pneumococcal antibodies had been measured with two enzyme-linked immunosorbent assays (ELISAs), one overall assay (OA) using the 23-valent pneumococcal polysaccharide vaccine (23-PPSV) as detecting antigen and the other purified pneumococcal polysaccharide serotypes (serotype-specific assay, SSA) (serotypes 14, 19F and 23F). Antibody levels were measured before (n = 176) and after (n = 93) immunization with the 23-PPSV. Before immunization, low titres were found for 138 of 176 patients (78%) with OA, compared to 20 of 176 patients (11%) with the SSA. We found a significant correlation between OA and SSA results. After immunization, 88% (71 of 81) of the patients considered as responders in the OA test were also responders in the SSA; 93% (71 of 76) of the patients classified as responders according to the SSA were also responders in the OA. SPAD was diagnosed in 8% (seven of 93) of patients on the basis of the absence of response in both tests. Thus, we propose to use OA as a screening test for SPAD before 23-PPSV immunization. After immunization, SSA should be used only in case of a low response in OA. Only the absence of or a very low antibody response detected by both tests should be used as a diagnostic criterion for SPAD.

What is the effect of systemic anticancer treatment on cognitive function?

Treatment regimens for solid tumours have been extensively investigated for their physical toxic effects, but far less is known about the potential impairment of cognitive function by anticancer treatment regimens. Here, we review published studies that examined cognitive function in adult patients receiving systemic therapy for solid tumours. Our review suggests that patients can experience cognitive changes related to their treatment. However, several studies had methodological limitations, such as use of a limited sample size, lack of baseline assessment, and lack of control for potential confounding factors. Better designed clinical trials are required so that the difficulties patients face in terms of reduced cognitive function as a result of anticancer treatment can be fully elucidated. These trials should have sufficient statistical power and, importantly, should also be prospective.

Risk communication in clinical trials: a cognitive experiment and a survey.

BACKGROUND: A Royal Statistical Society Working Party recently recommended that "Greater use should be made of numerical, as opposed to verbal, descriptions of risk" in first-in-man clinical trials. This echoed the view of many clinicians and psychologists about risk communication. As the clinical trial industry expands rapidly across the globe, it is important to understand risk communication in Asian countries. METHODS: We conducted a cognitive experiment about participation in a hypothetical clinical trial of a pain relief medication and a survey in cancer and arthritis patients in Singapore. In part 1 of the experiment, the patients received information about the risk of side effects in one of three formats (frequency, percentage and verbal descriptor) and in one of two sequences (from least to most severe and from most to least severe), and were asked about their willingness to participate. In part 2, the patients received information about the risk in all three formats, in the same sequence, and were again asked about their willingness to participate. A survey of preference for risk presentation methods and usage of verbal descriptors immediately followed. RESULTS: Willingness to participate and the likelihood of changing one's decision were not affected by the risk presentation methods. Most patients indicated a preference for the frequency format, but patients with primary school or no formal education were indifferent. While the patients used the verbal descriptors "very common", "common" and "very rare" in ways similar to the European Commission's Guidelines, their usage of the descriptors "uncommon" and "rare" was substantially different from the EU's. CONCLUSION: In this sample of Asian cancer and arthritis patients, risk presentation format had no impact on willingness to participate in a clinical trial. However, there is a clear preference for the frequency format. The lay use of verbal descriptors was substantially different from the EU's.

Beyond signaling and human capital: Education and the revelation of ability

We provide evidence that college graduation plays a direct role in revealing ability to the labor market. Using the NLSY79, our results suggest that ability is observed nearly perfectly for college graduates, but is revealed to the labor market more gradually for high school graduates. Consequently, from the beginning of their careers, college graduates are paid in accordance with their own ability, while the wages of high school graduates are initially unrelated to their own ability. This view of ability revelation in the labor market has considerable power in explaining racial differences in wages, education, and returns to ability.

Differences in the cognitive skills of bonobos and chimpanzees.

While bonobos and chimpanzees are both genetically and behaviorally very similar, they also differ in significant ways. Bonobos are more cautious and socially tolerant while chimpanzees are more dependent on extractive foraging, which requires tools. The similarities suggest the two species should be cognitively similar while the behavioral differences predict where the two species should differ cognitively. We compared both species on a wide range of cognitive problems testing their understanding of the physical and social world. Bonobos were more skilled at solving tasks related to theory of mind or an understanding of social causality, while chimpanzees were more skilled at tasks requiring the use of tools and an understanding of physical causality. These species differences support the role of ecological and socio-ecological pressures in shaping cognitive skills over relatively short periods of evolutionary time.

The impact of anxiety-inducing distraction on cognitive performance: a combined brain imaging and personality investigation.

BACKGROUND: Previous investigations revealed that the impact of task-irrelevant emotional distraction on ongoing goal-oriented cognitive processing is linked to opposite patterns of activation in emotional and perceptual vs. cognitive control/executive brain regions. However, little is known about the role of individual variations in these responses. The present study investigated the effect of trait anxiety on the neural responses mediating the impact of transient anxiety-inducing task-irrelevant distraction on cognitive performance, and on the neural correlates of coping with such distraction. We investigated whether activity in the brain regions sensitive to emotional distraction would show dissociable patterns of co-variation with measures indexing individual variations in trait anxiety and cognitive performance. METHODOLOGY/PRINCIPAL FINDINGS: Event-related fMRI data, recorded while healthy female participants performed a delayed-response working memory (WM) task with distraction, were investigated in conjunction with behavioural measures that assessed individual variations in both trait anxiety and WM performance. Consistent with increased sensitivity to emotional cues in high anxiety, specific perceptual areas (fusiform gyrus--FG) exhibited increased activity that was positively correlated with trait anxiety and negatively correlated with WM performance, whereas specific executive regions (right lateral prefrontal cortex--PFC) exhibited decreased activity that was negatively correlated with trait anxiety. The study also identified a role of the medial and left lateral PFC in coping with distraction, as opposed to reflecting a detrimental impact of emotional distraction. CONCLUSIONS: These findings provide initial evidence concerning the neural mechanisms sensitive to individual variations in trait anxiety and WM performance, which dissociate the detrimental impact of emotion distraction and the engagement of mechanisms to cope with distracting emotions. Our study sheds light on the neural correlates of emotion-cognition interactions in normal behaviour, which has implications for understanding factors that may influence susceptibility to affective disorders, in general, and to anxiety disorders, in particular.

One sound or two? Object-related negativity indexes echo perception.

The ability to isolate a single sound source among concurrent sources and reverberant energy is necessary for understanding the auditory world. The precedence effect describes a related experimental finding, that when presented with identical sounds from two locations with a short onset asynchrony (on the order of milliseconds), listeners report a single source with a location dominated by the lead sound. Single-cell recordings in multiple animal models have indicated that there are low-level mechanisms that may contribute to the precedence effect, yet psychophysical studies in humans have provided evidence that top-down cognitive processes have a great deal of influence on the perception of simulated echoes. In the present study, event-related potentials evoked by click pairs at and around listeners' echo thresholds indicate that perception of the lead and lag sound as individual sources elicits a negativity between 100 and 250 msec, previously termed the object-related negativity (ORN). Even for physically identical stimuli, the ORN is evident when listeners report hearing, as compared with not hearing, a second sound source. These results define a neural mechanism related to the conscious perception of multiple auditory objects.

Cardiorespiratory fitness and cognitive function in midlife: neuroprotection or neuroselection?

OBJECTIVE: A study was undertaken to determine whether better cognitive functioning at midlife among more physically fit individuals reflects neuroprotection, by which fitness protects against age-related cognitive decline, or neuroselection, by which children with higher cognitive functioning select more active lifestyles. METHODS: Children in the Dunedin Longitudinal Study (N = 1,037) completed the Wechsler Intelligence Scales and the Trail Making, Rey Delayed Recall, and Grooved Pegboard tasks as children and again at midlife (age = 38 years). Adult cardiorespiratory fitness was assessed using a submaximal exercise test to estimate maximum oxygen consumption adjusted for body weight in milliliters/minute/kilogram. We tested whether more fit individuals had better cognitive functioning than their less fit counterparts (which could be consistent with neuroprotection), and whether better childhood cognitive functioning predisposed to better adult cardiorespiratory fitness (neuroselection). Finally, we examined possible mechanisms of neuroselection. RESULTS: Participants with better cardiorespiratory fitness had higher cognitive test scores at midlife. However, fitness-associated advantages in cognitive functioning were already present in childhood. After accounting for childhood baseline performance on the same cognitive tests, there was no association between cardiorespiratory fitness and midlife cognitive functioning. Socioeconomic and health advantages in childhood and healthier lifestyles during young adulthood explained most of the association between childhood cognitive functioning and adult cardiorespiratory fitness. INTERPRETATION: We found no evidence for a neuroprotective effect of cardiorespiratory fitness as of midlife. Instead, children with better cognitive functioning are selecting healthier lives. Fitness interventions may enhance cognitive functioning. However, observational and experimental studies testing neuroprotective effects of physical fitness should consider confounding by neuroselection.

The impact of the developmental timing of trauma exposure on PTSD symptoms and psychosocial functioning among older adults.

The present study examined the impact of the developmental timing of trauma exposure on posttraumatic stress disorder (PTSD) symptoms and psychosocial functioning in a large sample of community-dwelling older adults (N = 1,995). Specifically, we investigated whether the negative consequences of exposure to traumatic events were greater for traumas experienced during childhood, adolescence, young adulthood, midlife, or older adulthood. Each of these developmental periods is characterized by age-related changes in cognitive and social processes that may influence psychological adjustment following trauma exposure. Results revealed that older adults who experienced their currently most distressing traumatic event during childhood exhibited more severe symptoms of PTSD and lower subjective happiness compared with older adults who experienced their most distressing trauma after the transition to adulthood. Similar findings emerged for measures of social support and coping ability. The differential effects of childhood compared with later life traumas were not fully explained by differences in cumulative trauma exposure or by differences in the objective and subjective characteristics of the events. Our findings demonstrate the enduring nature of traumatic events encountered early in the life course and underscore the importance of examining the developmental context of trauma exposure in investigations of the long-term consequences of traumatic experiences.

Memory and coping with stress: the relationship between cognitive-emotional distinctiveness, memory valence, and distress.

Cognitive-emotional distinctiveness (CED), the extent to which an individual separates emotions from an event in the cognitive representation of the event, was explored in four studies. CED was measured using a modified multidimensional scaling procedure. The first study found that lower levels of CED in memories of the September 11 terrorist attacks predicted greater frequency of intrusive thoughts about the attacks. The second study revealed that CED levels are higher in negative events, in comparison to positive events and that low CED levels in emotionally intense negative events are associated with a pattern of greater event-related distress. The third study replicated the findings from the previous study when examining CED levels in participants' memories of the 2004 Presidential election. The fourth study revealed that low CED in emotionally intense negative events is associated with worse mental health. We argue that CED is an adaptive and healthy coping feature of stressful memories.

Frontal-striatal circuits in cognitive aging: Evidence for caudate involvement

Changes in cognition with aging have been claimed to be due in large part to a decline in frontal lobe function. However, at our present state of knowledge, the emphasis on the frontal lobes to the exclusion of the rest of the frontal-striatal circuits of which they are a part is unwarranted. To argue this point, I consider another anatomical candidate within these circuits, the caudate. Evidence is presented that the caudate decreases in size with age as much as the frontal lobes and that damage to either the frontal lobes or the caudate is accompanied by declines in inhibitory processes, executive control, and cognitive speed similar to those seen in normal aging. Separating the unique contributions of the frontal lobes and the caudate to these circuits is difficult but should be the focus of future studies of the biological basis of cognitive aging.

Cognitive control of movement via the cerebellar-recipient thalamus.

The cognitive control of behavior was long considered to be centralized in cerebral cortex. More recently, subcortical structures such as cerebellum and basal ganglia have been implicated in cognitive functions as well. The fact that subcortico-cortical circuits for the control of movement involve the thalamus prompts the notion that activity in movement-related thalamus may also reflect elements of cognitive behavior. Yet this hypothesis has rarely been investigated. Using the pathways linking cerebellum to cerebral cortex via the thalamus as a template, we review evidence that the motor thalamus, together with movement-related central thalamus have the requisite connectivity and activity to mediate cognitive aspects of movement control.