Weak pairwise correlations imply strongly correlated network states in a neural population

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher order interactions among large groups of elements play an important role. In the vertebrate retina, we show that weak correlations between pairs of neurons coexist with strongly collective behavior in the responses of ten or more neurons. Surprisingly, we find that this collective behavior is described quantitatively by models that capture the observed pairwise correlations but assume no higher order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behavior. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.Comment: Full account of work presented at the conference on Computational and Systems Neuroscience (COSYNE), 17-20 March 2005, in Salt Lake City, Utah (http://cosyne.org

Depressive symptoms during rehabilitation period predict poor outcome of lumbar spinal stenosis surgery: A two-year perspective

<p>Abstract</p> <p>Background</p> <p>Previous research has shown an association between preoperative depressive symptoms and a poorer surgery outcome in lumbar spinal stenosis (LSS). It is not known whether depressive symptoms throughout the recovery period are relevant to the outcome of surgery in LSS. In this prospective clinical study the predictive value of preoperative and postoperative depressive symptoms with respect to the surgery outcome is reported.</p> <p>Methods</p> <p>96 patients (mean age 62 years) with symptomatic lumbar spinal stenosis underwent decompressive surgery. They completed the same set of questionnaires preoperatively and 3 months, 6 months, 1 year and 2 years postoperatively. Depressive symptoms were assessed with the 21-item Beck Depression Inventory. Physical functioning and pain were assessed with the Oswestry Disability Index, the Stucki Questionnaire, self-reported walking ability and VAS rating. Logistic regression analyses were used to examine the predictive value of preoperative and postoperative depressive symptoms regarding the surgery outcome. A "good" outcome was defined in two ways: first, by gaining a 30% improvement in relation to the preoperative disability and pain, and second, by having a score at or below the median value for disability and pain on 2-year follow-up.</p> <p>Results</p> <p>Having elevated depressive symptoms particularly on 3-month follow-up was predictive of a poorer surgery outcome regarding pain and disability: when the outcome was defined as less than 30% improvement from the baseline, the OR's (with 95% confidence intervals) were 2.94 (1.06-8.12), <0.05 for Oswestry and 3.33 (1.13-9.79), <0.05 for VAS. In median split approach the OR was 4.11 (1.27-13.32), <0.05 for Oswestry. Predictive associations also emerged between having depressive symptoms on 6-month and 1-year follow-ups and a poorer outcome regarding disability. The predictive value of elevated depressive symptoms particularly with respect to 2-yeard disability was evident whether the outcome was defined as a 30% improvement compared to the preoperative status or as belonging to the better scoring half of the study population on 2-year follow-up.</p> <p>Conclusions</p> <p>Preoperative and postoperative depressive symptoms may indicate those patients at greater risk of a poorer postoperative functional ability. For these patients, further clinical evaluation should be carried out, especially during postoperative stages.</p

Development and Initial Validation of the PEG, a Three-item Scale Assessing Pain Intensity and Interference

Inadequate pain assessment is a barrier to appropriate pain management, but single-item “pain screening” provides limited information about chronic pain. Multidimensional pain measures such as the Brief Pain Inventory (BPI) are widely used in pain specialty and research settings, but are impractical for primary care. A brief and straightforward multidimensional pain measure could potentially improve initial assessment and follow-up of chronic pain in primary care. To develop an ultra-brief pain measure derived from the BPI. Development of a shortened three-item pain measure and initial assessment of its reliability, validity, and responsiveness. We used data from 1) a longitudinal study of 500 primary care patients with chronic pain and 2) a cross-sectional study of 646 veterans recruited from ambulatory care. Selected items assess average pain intensity (P), interference with enjoyment of life (E), and interference with general activity (G). Reliability of the three-item scale (PEG) was α = 0.73 and 0.89 in the two study samples. Overall, construct validity of the PEG was good for various pain-specific measures (r = 0.60–0.89 in Study 1 and r = 0.77–0.95 in Study 2), and comparable to that of the BPI. The PEG was sensitive to change and differentiated between patients with and without pain improvement at 6 months. We provide strong initial evidence for reliability, construct validity, and responsiveness of the PEG among primary care and other ambulatory clinic patients. The PEG may be a practical and useful tool to improve assessment and monitoring of chronic pain in primary care

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.