Dissociating top-down attentional control from selective perception and action.

Research into the neural mechanisms of attention has revealed a complex network of brain regions that are involved in the execution of attention-demanding tasks. Recent advances in human neuroimaging now permit investigation of the elementary processes of attention being subserved by specific components of the brain's attention system. Here we describe recent studies of spatial selective attention that made use of positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and event-related brain potentials (ERPs) to investigate the spatio-temporal dynamics of the attention-related neural activity. We first review the results from an event-related fMRI study that examined the neural mechanisms underlying top-down attentional control versus selective sensory perception. These results defined a fronto-temporal-parietal network involved in the control of spatial attention. Activity in these areas biased the neural activity in sensory brain structures coding the spatial locations of upcoming target stimuli, preceding a modulation of subsequent target processing in visual cortex. We then present preliminary evidence from a fast-rate event-related fMRI study of spatial attention that demonstrates how to disentangle the potentially overlapping hemodynamic responses elicited by temporally adjacent stimuli in studies of attentional control. Finally, we present new analyses from combined neuroimaging (PET) and event-related brain potential (ERP) studies that together reveal the timecourse of activation of brain regions implicated in attentional control and selective perception.

Conservative management of osteomyelitis in the feet of diabetic patients.

Experience of conservative management of osteomyelitis in a specialized, multidisciplinary, diabetic foot clinic was reviewed. The records of all patients attending the clinic over a 10-year period were examined retrospectively, and 22 patients with overt osteomyelitis were identified. Median age was 66 (31-87) years. In 12 cases the bone infection was a complication of a pre-existing ulcer; the most prevalent organism cultured from swabs was Staphylococcus aureus. The main site of infection was the first toe. The total duration of antibiotic treatment was 12 weeks (median, range 5-72), and clindamycin was the most commonly used oral agent. Four patients did not respond to initial conservative therapy and proceeded to amputation, while 1 patient responded clinically but had a recurrence of osteomyelitis at the same site 6 years later. In the remaining 17 patients resolution of osteomyelitis was achieved with conservative management over a median period of follow-up of 27 (range 5-73) months. The success of conservative therapy with prolonged courses of oral antibiotics challenges conventional advice that excision of infected bone is essential in the management of osteomyelitis affecting the foot in diabetes.

Covariations in ERP and PET measures of spatial selective attention in human extrastriate visual cortex.

In a previous study using positron emission tomography (PET), we demonstrated that focused attention to a location in the visual field produced increased regional cerebral blood flow in the fusiform gyrus contralateral to the attended hemifield (Heinze et al. [1994]: Nature 372:543). We related these effects to modulations in the amplitude of the P1 component (80-130 msec latency) of the visual event-related brain potentials (ERPs) recorded from the same subjects, under the identical stimulus and task conditions. Here, we replicate and extend these findings by showing that attention effects in the fusiform gyrus and the P1 component were similarly modulated by the perceptual load of the task. When subjects performed a perceptually demanding symbol-matching task within the focus of spatial attention, the fusiform activity and P1 component of the ERP were of greater magnitude than when the subjects performed a less perceptually demanding task that required only luminance detection at the attended location. In the latter condition, both the PET and ERP attention effects were reduced. In addition, in the present data significant activations were also obtained in the middle occipital gyrus contralateral to the attended hemifield, thereby demonstrating that multiple regions of extrastriate visual cortex are modulated by spatial attention. The findings of covariations between the P1 attention effect and activity in the posterior fusiform gyrus reinforce our hypothesis that common neural sources exist for these complementary, but very different measures of human brain activity.

Estimation of interpolation errors in scalp topographic mapping.

Topographic maps are commonly constructed from electrical scalp recordings (such as EEGs and ERPs) using several different interpolation methods. It is important to determine the accuracy of such maps. Previous assessments of interpolation methods have been based on global error measures and the visual appearance of the topographic maps. However, the relationship of interpolation error to local contributing factors requires a more detailed analysis. In this paper, we use simulations to explore and quantify the relationship of error to global and local factors for different interpolation methods. We find that among the best interpolation methods, adequate electrode density is more important than the method used. For shallow sources, we show that local interpolation error is most correlated with potential gradient, and has a lesser correlation with distance to nearest electrode. The greatest correlation, however, is with the product of gradient and distance. Thus, interpolation error can be controlled locally by making the interelectrode distance inversely proportional to the expected potential gradient. With shallow sources, areas far from any electrode and having high apparent gradient are likely to have high interpolation error. Moreover, all areas far from any electrode may contain high interpolation errors, and should be interpreted with caution.

The description and classification of diabetic foot lesions.

Diabetic foot ulcers are of many types and different ulcers require management in different ways. Their optimal management is currently hindered by lack of a useful working classification. Such a classification must be flexible enough to be applied to all lesions likely to be encountered but specific enough to enable clear definition of an individual lesion. It must also be simple enough to ensure that it is understood by all categories of health care workers, whether specialist or not. An attempt has been made to devise a classification--based on the key elements used in describing foot lesions--and it is put forward to act as stimulus for debate. It is based on the clinical definition of infection, ischaemia, and neuropathy. Although two of these, or even all three, may be found in the same foot, they should be considered in the order given because this reflects the sequence of clinical decisions which should be made. The adoption of a classification such as this would aid education, communication, research and audit, and would lead to better management of ulcers.

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome.

The density of serotonin reuptake receptors on peripheral platelets from 22 patients with primary fibromyalgia syndrome (FS) and the serum serotonin concentrations in 9 patients with FS were compared with those of matched healthy controls. The mean serum serotonin concentration was lower (p = 0.01) in FS than in controls, while the binding of 3H-imipramine was higher (p = 0.035) and normalized with treatment using a combination of ibuprofen and alprazolam. Improvement in selected clinical measures of FS disease activity during treatment correlated with the change in platelet 3H-imipramine binding. These findings support the proposed hypothesis of aberrant pain perception in FS resulting from a deficiency of serotonin.

Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam. A double-blind, placebo-controlled study.

A multidimensional evaluation of 78 patients with primary fibrositis/fibromyalgia syndrome (PFS) revealed no significant relationship between clinical measures of physical discomfort and psychological measures. This observation provided evidence against the notion that the pain of PFS has a psychological etiology. The same patients were randomized into 4 groups for treatment with ibuprofen and/or alprazolam in a randomized, double-blind, double-dummy, placebo-controlled pilot trial. Clinical improvement in patient rating of disease severity and in the severity of tenderness upon palpation was most apparent in the subgroup of patients who were receiving both ibuprofen and alprazolam. An 8-week, open-label study in which 52 patients received both drugs further documented improvement in outcome measures. These data indicate that treatment with a combination of ibuprofen and alprazolam can be beneficial for some patients with PFS.

Psychological stress and the fibrositis/fibromyalgia syndrome.

The relationship of stress and social support to the fibrositis/fibromyalgia syndrome (FS) was investigated by administration of 4 questionnaire instruments to 28 patients with FS, 20 patients with rheumatoid arthritis (RA) and 28 pain-free normal controls. FS showed higher levels of stress as measured by daily "hassles" than did RA or controls. However, on a measure of major life stress, they reported lower levels. No differences were found between groups with regard to daily "uplifts" or social support. Correlations between those measures of stress and social support with their scores on the Arthritis Impact Measurement Scale showed that the Hassles Scale was significantly related to the AIMS Psychological component.

Serum amino acids in fibrositis/fibromyalgia syndrome.

Free plasma tryptophan levels in patients with fibrositis syndrome were measured by Moldofsky and Warsh with the view that the pathogenesis of fibrositis syndrome might involve a functional deficiency of serotonin. The hypothesis was supported by the finding of an inverse relationship between tryptophan concentration and the severity of musculoskeletal pain. Our study examined the total serum amino acid pool in fibrositis syndrome. Twenty patients with primary fibrositis syndrome and matched normal controls were evaluated clinically. After denaturation of macromolecules, serum amino acids were quantitated by automated analysis. Patients with fibrositis syndrome exhibited significantly lower levels of total serum tryptophan (p = 0.002), as well as 6 other amino acids: alanine (p less than 0.0005), histidine (p = 0.001), lysine (p = 0.02), proline (p = 0.039), serine (p = 0.028), and threonine (p = 0.013). These findings support the serotonin deficiency hypothesis for fibrositis syndrome pathogenesis but also imply a more generalized defect in amino acid homeostasis among affected individuals.