How reliable are MEG resting-state connectivity metrics?

MEG offers dynamic and spectral resolution for resting-state connectivity which is unavailable in fMRI. However, there are a wide range of available network estimation methods for MEG, and little in the way of existing guidance on which ones to employ. In this technical note, we investigate the extent to which many popular measures of stationary connectivity are suitable for use in resting-state MEG, localising magnetic sources with a scalar beamformer. We use as empirical criteria that network measures for individual subjects should be repeatable, and that group-level connectivity estimation shows good reproducibility. Using publically-available data from the Human Connectome Project, we test the reliability of 12 network estimation techniques against these criteria. We find that the impact of magnetic field spread or spatial leakage artefact is profound, creates a major confound for many connectivity measures, and can artificially inflate measures of consistency. Among those robust to this effect, we find poor test-retest reliability in phase- or coherence-based metrics such as the phase lag index or the imaginary part of coherency. The most consistent methods for stationary connectivity estimation over all of our tests are simple amplitude envelope correlation and partial correlation measures.

A symmetric multivariate leakage correction for MEG connectomes.

Ambiguities in the source reconstruction of magnetoencephalographic (MEG) measurements can cause spurious correlations between estimated source time-courses. In this paper, we propose a symmetric orthogonalisation method to correct for these artificial correlations between a set of multiple regions of interest (ROIs). This process enables the straightforward application of network modelling methods, including partial correlation or multivariate autoregressive modelling, to infer connectomes, or functional networks, from the corrected ROIs. Here, we apply the correction to simulated MEG recordings of simple networks and to a resting-state dataset collected from eight subjects, before computing the partial correlations between power envelopes of the corrected ROItime-courses. We show accurate reconstruction of our simulated networks, and in the analysis of real MEGresting-state connectivity, we find dense bilateral connections within the motor and visual networks, together with longer-range direct fronto-parietal connections.

Dysfunction of natural killer activity in a family with chronic fatigue syndrome.

A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry. NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood. Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.

Endogenous opioids inhibit ambulatory blood pressure during naturally occurring stress.

OBJECTIVE: Laboratory experiments suggest that endogenous opioids inhibit blood pressure responses during psychological stress. Moreover, there seem to be considerable individual differences in the efficacy of opioid blood pressure inhibition, and these differences may be involved in the expression of risk for cardiovascular disease. To further evaluate the possible role of opioid mechanisms in cardiovascular control, the present study sought to document the effects of the long-lasting oral opioid antagonist naltrexone (ReVia, DuPont, Wilmington, DE) on ambulatory blood pressure responses during naturally occurring stress. METHOD: Thirty male volunteers participated in a laboratory stress study using naltrexone followed by ambulatory blood pressure under placebo and during the subsequent 24-hour period. Within-subject analyses were performed on ambulatory blood pressures under placebo and naltrexone conditions. RESULTS: Laboratory results indicate no significant group effects of naltrexone on blood pressure levels or reactivity. Ambulatory results indicate that during periods of low self-reported stress, no effect of opioid blockade was apparent. In contrast, during periods of high stress, opioid blockade increased ambulatory blood pressure. CONCLUSIONS: These findings suggest that naltrexone-sensitive opioid mechanisms inhibit ambulatory blood pressure responses during naturally occurring stress.

Relaxation training and opioid inhibition of blood pressure response to stress.

The present study was designed to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Opioid mechanisms were assessed by examination of the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and after relaxation training. Thirty-two young men with mildly elevated casual arterial pressure were recruited for placebo-controlled naltrexone stress tests and relaxation training. The results indicated that relaxation training significantly reduced the diastolic pressure response to mental arithmetic stress. Opioid receptor blockade with naltrexone antagonized the effects of relaxation training. These findings suggest that some of the physiological effects of relaxation training are mediated by augmentation of inhibitory opioid mechanisms.

Elderly people's knowledge of and attitudes to pain management.

Pain is a frequent complaint of elderly people in hospitals and in the community, yet it is often not managed effectively. Barriers to effective management have included fear of narcotic addiction, inadequate assessment of pain, and attitudes of health professionals. Attempts have been made to improve the knowledge and attitudes of health-care professionals. This study examined the attitudes and knowledge of acute pain and pain management among well elderly people in rural and urban settings in the southeastern USA in order to identify possible barriers to effective pain management. Questionnaires on knowledge and attitudes towards pain and pain management were given to 62 rural and 63 urban well elderly people aged 65 years and older. Findings demonstrate a lack of knowledge as well as the presence of non-facilitative attitudes about pain and pain management.

Psychological coping with acute pain: an examination of the role of endogenous opioid mechanisms.

This study examined the relationship among endogenous opioids, Monitoring and Blunting coping styles, and acute pain responses. Fifty-eight male subjects underwent a 1-min pressure pain stimulus during two laboratory sessions. Subjects experienced this pain stimulus once under endogenous opioid blockade with naltrexone and once in a placebo condition. Blunting was found to be negatively correlated with pain ratings, but this relationship was significantly more prominent under opioid blockade. Results for coping behaviors subjects used to manage the experimental pain were generally consistent with the Blunting results, indicating that cognitive coping was related more strongly to decreased pain ratings and cardiovascular stress responsiveness under opioid blockade. Overall, the beneficial effects of Blunting and cognitive coping on pain responses did not depend upon endogenous opioids and, in fact, became stronger when opioid receptors were blocked. The relationship between endogenous opioids and coping appears to be dependent upon situational and stimulus characteristics.

Comparison of morphine and morphine with ketamine for postoperative analgesia.

PURPOSE: The purpose of this study was to compare morphine with ketamine to morphine alone in a double-blind investigation of postsurgical pain control. METHODS: Forty-two ASA 1 and 2 patients undergoing elective microdiscectomy were administered either 1 mg.ml-1 of morphine (n = 20) or 1 mg.ml-1 of both morphine and ketamine (n = 22) via iv patient controlled analgesia (IVPCA). Pain relief and side effects were assessed at 24 hr after surgery. RESULTS: The mean (SD) visual analogue scale (VAS) pain rating of 2.3 (1.67) for patients receiving morphine with ketamine was lower (P < 0.001) than the VAS scores of patients receiving only morphine 4.5 (1.54). Patients receiving morphine and ketamine also had less difficulty with side effects, reporting less nausea (P < 0.05), pruritus (P < 0.001), and urinary retention (P < 0.05). Although dysphoria is reported to be a common side effect of ketamine, complaints of dysphoria were rare in both groups, with only one subject (5%) in the morphine with ketamine group and three (15%) subjects receiving morphine alone reporting this side effect. CONCLUSION: IVPCA ketamine in combination with morphine provides superior postsurgical pain relief at lower dosage and with fewer side effects than morphine alone.

The psychobiology of hostility: possible endogenous opioid mechanisms.

This study examined the role of endogenous opioids in the relation between hostility and cardiovascular stress responsiveness. Forty-six men completed the Cook-Medley Hostility Scale and experienced a laboratory pain stressor once under opioid blockade and once under placebo. Hostility scores were significantly related to the magnitude of change in cardiovascular reactivity/recovery resulting from opioid blockade. Low scorers on the Cynicism subscale displayed increases in heart rate (HR) reactivity under blockade relative to placebo, with reactivity decreases noted in high scorers. Low Hostile Affect scores were similarly associated with impaired diastolic blood pressure recovery under opioid blockade. HR recovery results were somewhat different, with high scorers on Aggressive Responding and the total Cook-Medley displaying improved HR recovery under opioid blockade, with no change noted in low scorers. These data provide preliminary support for the hypothesis that low hostile individuals rely on endogenous opioids for buffering cardiovascular stress responsiveness, but high hostiles do not.

Elderly hospice patients' perspective on pain management.

The literature reports that 70% of cancer patients with advanced disease experience pain. Even with increased emphasis on research and education, problems with effective pain management are still evident. Hospice patients' knowledge and attitudes about pain may contribute to this complex problem. To gain an understanding of hospice patients' perspective on the management of pain, 57 hospice patients were asked to describe their knowledge of pain management and their attitudes toward controlling pain. Results showed non-facilitative attitudes and gaps in knowledge that may contribute to ineffective pain management among hospice patients.

Cardiorespiratory effects of premedication for children.

Cardiovascular and respiratory effects of pediatric preanesthetic premedication have received only minimal attention, probably because most children tolerate such drugs without apparent ill effect. In children with congenital heart disease or other serious illness, there is often reluctance to use premedication. We sought to determine whether different premedication regimens produced significant cardiorespiratory effect. A randomized prospective study of the cardiovascular and respiratory effects of different oral, nasal, and rectal premedication regimens was conducted. Fifty-eight young children (average age 2.7 yr) were studied. Oral meperidine (3 mg/kg) with pentobarbital (4 mg/kg) decreased heart rate, mean arterial pressure, cardiac index, respiratory rate, and oxygen saturation. Stroke volume was maintained. Nasal ketamine (5 mg/kg) with midazolam (0.2 mg/kg) produced no significant cardiovascular or respiratory effects. Rectal methohexital (30 mg/kg) increased heart rate with a coincident decrease in stroke volume but had no other positive or negative cardiac or respiratory effect. This information documents disparate cardiorespiratory effects of different preanesthetic medications in normal children.

Temporal analysis of the antibody response to HIV envelope protein in HIV-infected laboratory workers.

Three laboratory workers have been infected with the IIIB strain of HIV; their antibody response to HIV has been studied in serial serum specimens. Because the infecting virus is known, the fine specificity of the antibody response was studied on the homologous strain of HIV. Anti-p17, anti-p24, anti-gp160, CD4/gp120 blocking and neutralizing antibodies developed in parallel. Epitope mapping of the anti-gp160 response indicated several regions that consistently induced an antibody response. Serum contained antibody which reacted with V3-specific peptides corresponding to the very tip of the loop and crossreactivity was seen with V3 loop peptides from other sequence divergent strains of HIV. Antibody to the V1 loop was produced at levels comparable with that seen for the V3-loop. Anti-V1 neutralized HIV with a titration curve equivalent to an anti-V3 monoclonal antibody. Because the infecting virus is known and serial reisolates have been obtained, we explored the relationship between production of antibody to a given epitope and mutation in the virus. The data suggest that an association exists, but do not clearly indicate that antibody drives the selection for mutant viruses. The findings presented here provide a fine specificity analysis of the evolution of the antibody response to HIV in greater detail than has previously been performed.

The effect of ethnic differences on the pattern of HTLV-I-associated T-cell leukemia/lymphoma (HATL) in the United States.

Human T-cell lymphotropic virus Type I (HTLV-I) is the primary etiologic factor for adult T-cell leukemia/lymphoma (ATL). Although HTLV-I is endemic in Japan and the Caribbean islands, the reported clinical and epidemiologic features of ATL in these 2 parts of the world are quite different. ATL has been diagnosed at a younger age and is reported more frequently as the lymphomatous type rather than the acute type with leukemia in the Caribbean basin as compared with the presentation in Japan. In order to characterize ATL in the United States, a registry has been established at the National Cancer Institute for the purpose of recording all cases originally diagnosed in the United States. This registry was utilized to examine the effect of ethnic differences on age of onset and clinical features of ATL, using the same data base. Clinical and laboratory information was obtained from 177 patients suspected of having ATL, who were treated at the National Institutes of Health, or had biological samples sent for evaluation, or were reported in the literature. Histopathologic review and virologic studies were performed by standardized methods. Of 177 patients registered, 127 were considered as having ATL, according to an algorithm combining clinical, pathologic and laboratory features. Presenting features in the confirmed cases consisted primarily of lymphadenopathy (76.6%), hypercalcemia (72.5%), leukemia (82%), skin involvement (48.2%) and hepatomegaly (53.6%). Patients of Japanese ancestry were generally older (median age 63, range 51 to 73 years) than patients of African-American descent (median age 39, range 7 to 75 years) and presented more often with leukemia (90 vs. 69%).(ABSTRACT TRUNCATED AT 250 WORDS)

Nursing knowledge: acute postoperative pain management in the elderly.

1. The inadequate management of acute postoperative pain among adults is well documented. Studies have shown that 75% or more of hospitalized adult patients following surgery suffer moderate or intense pain even with the use of analgesics. Also, physicians under-prescribe narcotic analgesics and nurses administer less than the patient could receive. 2. Nurses' ineffective approaches to the management of pain have been attributed to inappropriate fears of addiction and respiratory depression, rigid attitudes regarding what constitutes adequate pain relief, and misunderstandings about the physiologic and psychologic components of pain. 3. The results of this study support McCaffery's (1989) finding that nurses do not understand the effective use of narcotics in relation to pain management.