Attentional bias modification for acute experimental pain: A randomized controlled trial of retraining early versus later attention on pain severity, threshold and tolerance.

BACKGROUND: Noxious attentional bias is thought to confer vulnerability to pain, suggesting that modifying the bias could reduce pain outcomes. Herein is presented a randomized controlled trial to test the effects of retraining the dot probe attentional bias at short versus long stimulus durations towards neutral stimuli, and away from threat stimuli, on acute pain experience, in comparison with a placebo control group. METHODS: Eighty-one pain-free volunteers, blinded to condition, were randomized to complete either one of two neutral bias modification programs in which words were presented for 500 ms (ABM-500; n = 28) or 1250 ms (ABM-1250; n = 26), or to a sham training program that included both stimulus durations (ABM-Placebo; n = 27). Testing took place in a university laboratory. At post-training, participants completed the pain-inducing 'cold pressor task', and measures of pain severity, threshold and tolerance were taken. Attentional bias was also measured at pre- and post-training. RESULTS: Findings indicated that ABM-500 reliably increased pain threshold and tolerance, in comparison with the control group. In contrast, ABM-1250 did not affect any of the pain outcomes. Expected ABM effects on attentional bias were not evident at the group level, but nevertheless ABM-500 bias reduction was significantly associated with increased pain tolerance. CONCLUSIONS: These findings suggest that retraining attention at short stimulus exposure durations is relatively more efficacious in promoting transfer of attentional retraining effects to real-world acute pain stressors, in comparison with both the longer stimulus duration and ABM-Placebo. SIGNIFICANCE: Testing of the impact of modifying maintained attentional bias on vulnerability to an acute pain stressor. Findings suggested that retraining rapid attentional bias using short exposure durations conferred greater analgesic benefit, in comparison with both the slower bias and sham-training.

Asymmetrical transfer effects of cognitive bias modification: Modifying attention to threat influences interpretation of emotional ambiguity, but not vice versa.

BACKGROUND AND OBJECTIVES: It is well established that attention bias and interpretation bias each have a key role in the development and continuation of anxiety. How the biases may interact with one another in anxiety is, however, poorly understood. Using cognitive bias modification techniques, the present study examined whether training a more positive interpretation bias or attention bias resulted in transfer of effects to the untrained cognitive domain. Differences in anxiety reactivity to a real-world stressor were also assessed. METHODS: Ninety-seven first year undergraduates who had self-reported anxiety were allocated to one of four groups: attention bias training (n = 24), interpretation bias training (n = 26), control task training (n = 25) and no training (n = 22). Training was computer-based and comprised eight sessions over four weeks. Baseline and follow-up measures of attention and interpretation bias, anxiety and depression were taken. RESULTS: A significant reduction in threat-related attention bias and an increase in positive interpretation bias occurred in the attention bias training group. The interpretation bias training group did not exhibit a significant change in attention bias, only interpretation bias. The effect of attention bias training on interpretation bias was significant as compared with the two control groups. There were no effects on self-report measures. LIMITATIONS: The extent to which interpretive training can modify attentional processing remains unclear. CONCLUSIONS: Findings support the idea that attentional training might have broad cognitive consequences, impacting downstream on interpretive bias. However, they do not fully support a common mechanism hypothesis, as interpretive training did not impact on attentional bias.

The reversible cerebral vasoconstriction syndrome in association with venlafaxine and methenamine.

The reversible cerebral vasoconstriction syndrome (RCVS) is characterised by thunderclap headache and multifocal vasoconstriction of cerebral arteries on angiography. It is often drug induced, but it can occur postpartum, and as a result of a number of other precipitants. To make the diagnosis, it is necessary to exclude other causes of severe headache (such as aneurysmal subarachnoid haemorrhage, carotid dissection and primary angiitis of the central nervous system). However, it is also important to show that the vasoconstriction has resolved with repeat angiography at the 3-month stage. Here we report two cases of RCVS in association with venlafaxine and the urinary antiseptic, methenamine. Serotonin-norepinephrine reuptake inhibitors have recently been reported as a possible precipitant, but this is the first report to implicate methenamine. Although RCVS is relatively uncommon, it should be considered in the differential of those presenting with thunderclap headache.

Birth of a biome: insights into the assembly and maintenance of the Australian arid zone biota.

The integration of phylogenetics, phylogeography and palaeoenvironmental studies is providing major insights into the historical forces that have shaped the Earth's biomes. Yet our present view is biased towards arctic and temperate/tropical forest regions, with very little focus on the extensive arid regions of the planet. The Australian arid zone is one of the largest desert landform systems in the world, with a unique, diverse and relatively well-studied biota. With foci on palaeoenvironmental and molecular data, we here review what is known about the assembly and maintenance of this biome in the context of its physical history, and in comparison with other mesic biomes. Aridification of Australia began in the Mid-Miocene, around 15 million years, but fully arid landforms in central Australia appeared much later, around 1-4 million years. Dated molecular phylogenies of diverse taxa show the deepest divergences of arid-adapted taxa from the Mid-Miocene, consistent with the onset of desiccation. There is evidence of arid-adapted taxa evolving from mesic-adapted ancestors, and also of speciation within the arid zone. There is no evidence for an increase in speciation rate during the Pleistocene, and most arid-zone species lineages date to the Pliocene or earlier. The last 0.8 million years have seen major fluctuations of the arid zone, with large areas covered by mobile sand dunes during glacial maxima. Some large, vagile taxa show patterns of recent expansion and migration throughout the arid zone, in parallel with the ice sheet-imposed range shifts in Northern Hemisphere taxa. Yet other taxa show high lineage diversity and strong phylogeographical structure, indicating persistence in multiple localised refugia over several glacial maxima. Similar to the Northern Hemisphere, Pleistocene range shifts have produced suture zones, creating the opportunity for diversification and speciation through hybridisation, polyploidy and parthenogenesis. This review highlights the opportunities that development of arid conditions provides for rapid and diverse evolutionary radiations, and re-enforces the emerging view that Pleistocene environmental change can have diverse impacts on genetic structure and diversity in different biomes. There is a clear need for more detailed and targeted phylogeographical studies of Australia's arid biota and we suggest a framework and a set of a priori hypotheses by which to proceed.

Modern concept of vascular cognitive impairment.

BACKGROUND: Vascular cognitive impairment (VCI) has superseded vascular dementia and multi-infarct dementia as the concept to be used in cognitive decline due to cerebrovascular disease. METHOD: The literature was reviewed with regard to the concept of VCI and its incidence, pathophysiological substrate, clinical features and management. RESULTS: A change in the diagnostic paradigm from the current Alzheimer-based definition of vascular dementia to VCI will allow the earlier identification of cases and will identify a different population from that recognized using the current criteria for vascular dementia. CONCLUSIONS: Case identification at the earliest possible stage affords the greatest opportunity for treatment that may slow the rate of progression.

The concept of vascular cognitive impairment.

Vascular dementia (VaD) is increasingly recognised to reflect an outmoded concept in that it identifies cases too late for preventive therapy to have an opportunity to prevent the development of dementia and uses a cognitive paradigm inappropriately based on Alzheimer's disease. A replacement is urgently required and a new concept, that of vascular cognitive impairment (VCI), has been proposed to meet this need. It is imperative that criteria for VCI are developed on the basis of knowledge and data rather than supposition and assumption, as was the case for VaD. This review details the state of knowledge that we have now reached concerning the fundamental points of severity and cognitive paradigm and also covers a number of other imaging-related essential points embracing atrophy, leukoaraiosis, infarct volume and infarct location. Finally, the increasingly important concept of mixed dementia (co-existent Alzheimer's disease and VCI) is discussed.

Peripheral nerve granuloma in a patient with tuberculosis.

The cause of peripheral neuropathy associated with tuberculosis is controversial. Possibilities include an immune mediated neuropathy, direct invasion of nerves, vasculitic neuropathy, compressive neuropathy, a meningitic reaction, and the toxic effects of antituberculous chemotherapy. This report describes the unusual finding of granulomas in the peripheral nerve of a patient with tuberculosis. The pathological findings were of a delayed hypersensitivity reaction, but with no more specific indications of the mechanism of the neuropathy.

Profiles of cognitive decline in Alzheimer disease.

Most recent studies have used only two observations to estimate the rate of cognitive decline in patients with Alzheimer disease (AD); few have data taken from more than a 2-year period; and none report on autopsy-verified cases. Repeated observations over the complete course of the disease are necessary to quantitatively evaluate hypotheses such as the triphasic linear model of Brooks et al. (1993). The goal of this study is to compare the triphasic linear and quadratic models of decline in a group of 12 AD patients confirmed at autopsy with a group of age- and sex-matched normal control subjects. Both groups were taken from the University of Western Ontario Dementia Study, and the Extended Scale for Dementia was used as the outcome measure. The squared multiple correlation as a measure of goodness of fit suggested the superiority of the more parsimonious quadratic model over the triphasic linear model. Quantitative models more accurately reflect the profiles of change in AD and may prove more sensitive in measuring the effects of drugs on these patterns.

The cognitive syndrome of vascular dementia: implications for clinical trials.

Dementia is common among patients with cerebrovascular disease, particularly in a setting of one or more clinically evident strokes. Prior cohort and case studies have suggested that the cognitive syndrome of vascular dementia is characterized by predominant executive dysfunction, in contrast to the deficits in memory and language function that are typical of patients with Alzheimer disease. The course of cognitive decline may also differ between those dementia subtypes, with many, but not all, patients with vascular dementia exhibiting a stepwise course of decline caused by recurrent stroke and most patients with Alzheimer disease exhibiting a gradually progressive course of decline. The findings of prior studies of the cognitive syndrome of vascular dementia must be interpreted with caution, however, because of (1) possible inaccuracies in the determination of the dementia subtype and the loss of precision that might result from pooling heterogeneous subgroups of patients with vascular dementia, (2) difficulties inherent in identifying a pattern of strengths and weaknesses in patients who are required to have memory impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. Specific questions that should be addressed by future studies are discussed.

Conceptual background to vascular cognitive impairment.

The current criteria for vascular dementia use a paradigm that first diagnoses dementia on the basis of Alzheimer-type criteria and then superimposes upon this vascular events and risk factors to convert a diagnosis of Alzheimer disease to one of vascular dementia. There are two fundamental flaws with this approach. First, the neuropsychological features of Alzheimer disease are not the same as those for vascular dementia and so use of the current criteria will fail to diagnose many cases, particularly those in whom memory loss is not prominent. Second, progression of vascular dementia should be modifiable by adjustment of risk factors and, possibly, by the use of neuroprotective agents. Given this, it is absurd to wait until patients are frankly demented. It is far more appropriate to detect patients at risk of developing cognitive loss as soon as possible. This could be in the earliest symptomatic stage (vascular cognitive impairment) or even prior to this (brain-at-risk) stage. New criteria, based on evidence rather than on supposition, that focus on early disease are urgently needed.

Subtypes of vascular dementia.

The challenge of describing subgroups is particularly important in vascular dementia, which, in contrast to more stereotypic processes affecting cognitive function, is better thought of as several syndromes rather than as a disease. Many current diagnostic descriptions lack a strong empiric basis. Some of the categories now in use suffer from a priori assumptions about causality and pattern associations, which themselves have not been validated. The so-called mixed dementia syndrome may have been underrepresented in our estimation of dementia subtypes, in comparison with so-called pure vascular causes. Within the vascular syndrome, whether seen in isolation or in combination with other causes of dementia, the relative contributions of white matter changes as compared with multiple cortical strokes needs to be clarified. It remains a matter of controversy as to whether prolonged or chronic intermittent cerebral ischemia is a statistically important part of the dementia. The variable relation between clinical presentation and neuroimaging localization has important consequences for understanding the pathophysiology of cognitive impairment arising from vascular causes. Recent data also suggest that we should focus away from both the Alzheimer disease model of dementia and the multi-infarct model of vascular dementia. There are important opportunities available to clinicians from many disciplines to collaborate in precise clinical descriptions of large numbers of patients to advance our understanding of the spectrum of vascular cognitive impairment.

Imaging of static brain lesions in vascular dementia: implications for clinical trials.

Vascular dementia (VaD) relates to different vascular mechanisms and changes in the brain and has different causes and clinical manifestations, reflecting complex interactions between vascular etiologies, changes in the brain, host factors, and cognition. Critical elements to the concept and diagnosis of VaD are defining the vascular causes, the vascular etiologies, and changes in the brain. Verifying the relation between brain lesions and cognition (i.e., the extent to which brain changes cause, compound, or coexist with cognitive impairment) and establishing the types, extent, side, site, and tempo of brain lesions that relate to incident cognitive impairment are major diagnostic challenges. Previous work on interactions between brain lesion and cognition in to cerebrovascular disease (CVD) have shown variation in the definitions and measures of cognitive impairment, in the techniques and methods used to reveal different brain changes, and in the selection of patient populations. Furthermore, small sample sizes and the absence of multivariate statistics have been design limitations. Accordingly, the different sets of criteria used and methods applied identify different numbers and clusters of subjects and different distribution of brain changes. Furthermore, this heterogeneity is reflected in variation in natural history such as the rate of progression of decline in different cognitive domains over time. All these factors have hampered optimal designs of clinical drug trials. A summary of generalizations regarding lesion and cognition interaction in VaD can be made. (1) Not a single feature, but a combination of infarct features--extent and type of white matter lesions (WMLs), degree and site of atrophy, and host factor characteristics--constitues correlates of VaD. (2) Infarct features favoring VaD include bilaterality, multiplicity (>1), location in the dominant hemisphere, and location in the limbic structures (fronto- and mediolimbic). (3) WML features favoring VaD are extensive WMLs (extensive periventricular WMLs and confluent to extensive WMLs in the deep WM). (4) It is doubtful that only a single small lesion could provide imaging evidence for a diagnosis of VaD. (5) Absence of CVD lesions on computed tomography or magnetic resonance imaging is strong evidence against a diagnosis of VaD. In forthcoming protocols on CVD-associated cognitive impairment, the following brain imaging features should be specified: detailed characterization of brain changes; use of possible predefined subtypes based on brain imaging; use of rating of vascular burden; defining the type and extent of WMLs favoring a diagnosis of VaD; defining the extent of medial temporal lobe atrophy disfavoring a diagnosis of VaD; and technical harmonization of methods of scanning and analysis.