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\"Sixteen-year-old Austin, a self-described screw-up, finds out that his allegedly dead father happens to be the very-much-alive rock star Shane Tyler. Austin--a talented musician himself--is sucked into his newfound father's alluring music-biz orbit, pulling his true love, Josephine, along with him\"-- Provided by publisher.
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Causal role of the prefrontal cortex in top-down modulation of visual processing and working memory
This study uses a combination of TMS, fMRI and EEG to provide causal evidence for the role of the prefrontal cortex in the modulation of selective attention. Participants with greater decrement in visual association cortex modulation when TMS was used to knock out the prefrontal contribution had greater working memory performance decline.
Selective attention filters information to limit what is encoded and maintained in working memory. Although the prefrontal cortex (PFC) is central to both selective attention and working memory, the underlying neural processes that link these cognitive abilities remain elusive. Using functional magnetic resonance imaging to guide repetitive transcranial magnetic stimulation with electroencephalographic recordings in humans, we perturbed PFC function at the inferior frontal junction in participants before they performed a selective-attention, delayed-recognition task. This resulted in diminished top-down modulation of activity in posterior cortex during early encoding stages, which predicted a subsequent decrement in working memory accuracy. Participants with stronger fronto-posterior functional connectivity displayed greater disruptive effects. Our data further suggests that broad alpha-band (7–14 Hz) phase coherence subserved this long-distance top-down modulation. These results suggest that top-down modulation mediated by the prefrontal cortex is a causal link between early attentional processes and subsequent memory performance.
Journal Article
Bronchoscopic lung volume reduction with endobronchial valves for patients with heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi study): a randomised controlled trial
Lung volume reduction surgery improves survival in selected patients with emphysema, and has generated interest in bronchoscopic approaches that might achieve the same effect with less morbidity and mortality. Previous trials with endobronchial valves have yielded modest group benefits because when collateral ventilation is present it prevents lobar atelectasis.
We did a single-centre, double-blind sham-controlled trial in patients with both heterogeneous emphysema and a target lobe with intact interlobar fissures on CT of the thorax. We enrolled stable outpatients with chronic obstructive pulmonary disease who had a forced expiratory volume in 1 s (FEV1) of less than 50% predicted, significant hyperinflation (total lung capacity >100% and residual volume >150%), a restricted exercise capacity (6 min walking distance <450 m), and substantial breathlessness (MRC dyspnoea score ≥3). Participants were randomised (1:1) by computer-generated sequence to receive either valves placed to achieve unilateral lobar occlusion (bronchoscopic lung volume reduction) or a bronchoscopy with sham valve placement (control). Patients and researchers were masked to treatment allocation. The study was powered to detect a 15% improvement in the primary endpoint, the FEV1 3 months after the procedure. Analysis was on an intention-to-treat basis. The trial is registered at controlled-trials.com, ISRCTN04761234.
50 patients (62% male, FEV1 [% predicted] mean 31·7% [SD 10·2]) were enrolled to receive valves (n=25) or sham valve placement (control, n=25) between March 1, 2012, and Sept 30, 2013. In the bronchoscopic lung volume reduction group, FEV1 increased by a median 8·77% (IQR 2·27–35·85) versus 2·88% (0–8·51) in the control group (Mann-Whitney p=0·0326). There were two deaths in the bronchoscopic lung volume reduction group and one control patient was unable to attend for follow-up assessment because of a prolonged pneumothorax.
Unilateral lobar occlusion with endobronchial valves in patients with heterogeneous emphysema and intact interlobar fissures produces significant improvements in lung function. There is a risk of significant complications and further trials are needed that compare valve placement with lung volume reduction surgery.
Efficacy and Mechanism Evaluation Programme, funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.
Journal Article
Deficit in switching between functional brain networks underlies the impact of multitasking on working memory in older adults
Multitasking negatively influences the retention of information over brief periods of time. This impact of interference on working memory is exacerbated with normal aging. We used functional MRI to investigate the neural basis by which an interruption is more disruptive to working memory performance in older individuals. Younger and older adults engaged in delayed recognition tasks both with and without interruption by a secondary task. Behavioral analysis revealed that working memory performance was more impaired by interruptions in older compared with younger adults. Functional connectivity analyses showed that when interrupted, older adults disengaged from a memory maintenance network and reallocated attentional resources toward the interrupting stimulus in a manner consistent with younger adults. However, unlike younger individuals, older adults failed to both disengage from the interruption and reestablish functional connections associated with the disrupted memory network. These results suggest that multitasking leads to more significant working memory disruption in older adults because of an interruption recovery failure, manifest as a deficient ability to dynamically switch between functional brain networks.
Journal Article
Top-down modulation of visual feature processing: The role of the inferior frontal junction
Distinct areas within the visual association cortex are specialized for representing specific stimulus features, such as V4 for color and V5/hMT+ for motion. Recent studies have demonstrated that areas associated with attended features exhibit enhanced cortical activity, whereas those associated with ignored features elicit reduced activity. However, the source of this attentional (or top-down) modulation remains uncertain. A network of fronto-parietal cortical regions has been proposed as the prime candidate underlying this top-down modulation. Here, we evaluate whether there are distinct or overlapping top-down network regions for attention to different stimulus features. To this end, we explored functional magnetic resonance imaging (fMRI) functional connectivity data, electroencephalographic (EEG) source localization, and phase coherence that were obtained while participants attended or ignored motion and color stimuli. Functional connectivity analysis indicated that attention to color relies strongly on prefrontal regions, whereas attention to motion recruits both prefrontal and parietal areas. Although these networks are generally topologically segregated, both color and motion processes recruit right inferior frontal junction (IFJ). However, the IFJ may be more critical for color processing, as only connectivity with V4 predicted the degree of attentional modulation. Source localization at the time range of attentional modulation of the event related potential corroborated the role of the right IFJ and indicated that feature-based, top-down modulation occurs early during processing (< 200
ms post-stimulus onset). Furthermore, long-distance alpha (8–12
Hz) phase coherence between the IFJ and visual cortices may serve as a mechanism underlying anticipatory, top-down modulation of color feature processing.
► The right IFJ is recruited for feature-based (color and motion) top-down modulation. ► Except for IFJ, motion and color processing utilize distinct neural networks. ► Fronto-posterior alpha phase coherence may subserve top-down modulation. ► Neural modulation may be anticipatory as well as early during visual processing.
Journal Article
Idiopathic Pulmonary Fibrosis: Outcome in Relation to Smoking Status
The pathogenic importance of smoking status in idiopathic pulmonary fibrosis (IPF) is uncertain. In theory, increased oxidative stress in current and former smokers might promote disease progression. However, better survival has been reported for current smokers with IPF, although this might reflect less severe disease at presentation (a \"healthy smoker effect\").
To determine whether smoking status is associated with survival differences in IPF.
A total of 249 patients with IPF were studied (current smokers, n = 20; former smokers, n = 166; never-smokers, n = 63). Survival was evaluated against smoking status, using proportional hazards analysis, adjusting for sex, age, disease severity (extent of the disease on high-resolution computed tomography, composite physiologic index [CPI], percentage predicted diffusing capacity for carbon monoxide in separate models), and the degree of honeycombing.
Current smokers had milder disease than did former smokers, with lower CPI scores (P < 0.0001), less extensive disease on high-resolution computed tomography (P < 0.005), and higher unadjusted survival (hazard ratio = 0.44; 95% confidence interval = 0.24, 0.80; P = 0.007). However, survival did not differ between current and former smokers (P = 0.39) after adjustment for CPI levels. By contrast, the increase in survival seen in nonsmokers than in former smokers (hazard ratio = 0.51; 95% confidence interval = 0.41, 0.83; P = 0.008) was amplified (P < 0.0005) by adjustment for CPI levels.
In IPF, survival and severity-adjusted survival are higher in nonsmokers than in former smokers or the combined group of former and current smokers. By contrast, a better outcome in current smokers, compared with former smokers, reflects less severe disease at presentation and may represent a healthy smoker effect.
Journal Article
Idiopathic Pulmonary Fibrosis: A Composite Physiologic Index Derived from Disease Extent Observed by Computed Tomography
In idiopathic pulmonary fibrosis, the quantitation of disease severity using pulmonary function tests is often confounded by emphysema. We have identified the composite physiologic index (CPI) most closely reflecting the morphologic extent of pulmonary fibrosis. Consecutive patients with a clinical/computed tomography (CT) diagnosis of idiopathic pulmonary fibrosis (n = 212) were divided into group I (n = 106) and group II (n = 106). The CPI was derived in group I (by fitting pulmonary function tests against disease extent on CT) and was tested in Group II. The formula for the CPI was as follows: extent of disease on CT = 91.0 - (0.65 x percent predicted diffusing capacity for carbon monoxide [DLCO]) - (0.53 x percent predicted FVC) + (0.34 x percent predicted FEV1). In group II, the CPI correlated more strongly with disease extent on CT (r2 = 0.51) than the individual pulmonary function test (DLCO the highest value, r2 = 0.38). A subanalysis demonstrated that the better fit of the CPI was ascribable to a correction of the confounding effects of emphysema. Mortality was predicted more accurately by the CPI than by a pulmonary function test in all clinical subgroups, including a separate cohort of 36 patients with histologically proven usual interstitial pneumonia (CPI, p < 0.0005; FVC, p = 0.002; PO2, p = 0.002). In conclusion, a new CPI, derived against CT and validated using split sample testing, is a more accurate prognostic determinant in usual interstitial pneumonia than an individual pulmonary function test.
Journal Article
Left circumflex coronary artery from the pulmonary artery in scimitar syndrome
BackgroundScimitar syndrome is a rare combination of cardiopulmonary abnormalities found in 1–3 per 1000 live births. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is only found in 1 in 250–400 congenital heart disease patients.ObjectiveWe aimed to investigate the incidence of left circumflex ALCAPA within our referral center’s cohort of scimitar syndrome patients.Materials and methodsA review of medical records, cardiac imaging and operative notes from all patients diagnosed with scimitar syndrome at our center between 1992 and 2016 was undertaken and all imaging reviewed.ResultsFifty-four patients with scimitar syndrome and imaging were identified. Of these, 3 patients (1 male and 2 female) with ALCAPA were identified, representing an incidence of 5.5% (95% confidence interval [CI] 0–11.67%). In all three cases, the anomalous coronary arising from the pulmonary artery was the left circumflex coronary artery (LCx) and the point of origin was close to the pulmonary arterial bifurcation.ConclusionWe hypothesize that the prevalence of LCx-ALCAPA, in the setting of scimitar syndrome, may be greater than previously thought. We suggest that any patient with scimitar syndrome, especially with evidence of ischaemia, should be investigated for ALCAPA. Given its noninvasive nature and simultaneous imaging of the lungs, we suggest that cardiovascular CT is the most appropriate first-line investigation for these patients.
Journal Article
Clinical and economic consequences of non-cardiac incidental findings detected on cardiovascular computed tomography performed prior to transcatheter aortic valve implantation (TAVI)
Transcatheter aortic valve implantation (TAVI) is an effective treatment option for patients with severe degenerative aortic valve stenosis who are high risk for conventional surgery. Computed tomography (CT) performed prior to TAVI can detect pathologies that could influence outcomes following the procedure, however the incidence, cost, and clinical impact of incidental findings has not previously been investigated. 279 patients underwent CT; 188 subsequently had TAVI and 91 were declined. Incidental findings were classified as clinically significant (requiring treatment), indeterminate (requiring further assessment), or clinically insignificant. The primary outcome measure was all-cause mortality up to 3 years. Costs incurred by additional investigations resultant to incidental findings were estimated using the UK Department of Health Payment Tariff. Incidental findings were common in both the TAVI and medical therapy cohorts (54.8 vs. 70.3 %;
P
= 0.014). Subsequently, 45 extra investigations were recommended for the TAVI cohort, at an overall average cost of £32.69 per TAVI patient. In a univariate model, survival was significantly associated with the presence of a clinically significant or indeterminate finding (HR 1.61;
P
= 0.021). However, on multivariate analysis outcomes after TAVI were not influenced by any category of incidental finding. Incidental findings are common on CT scans performed prior to TAVI. However, the total cost involved in investigating these findings is low, and incidental findings do not independently identify patients with poorer outcomes after TAVI. The discovery of an incidental finding on CT should not necessarily influence or delay the decision to perform TAVI.
Journal Article
Technical feasibility and validation of a coronary artery calcium scoring system using CT coronary angiography images
Objectives
We validate a novel CT coronary angiography (CCTA) coronary calcium scoring system.
Methods
Calcium was quantified on CCTA images using a new patient-specific attenuation threshold: mean + 2SD of intra-coronary contrast density (HU). Using 335 patient data sets a conversion factor (CF) for predicting CACS from CCTA scores (CCTAS) was derived and validated in a separate cohort (
n
= 168). Bland–Altman analysis and weighted kappa for MESA centiles and Agatston risk groupings were calculated.
Results
Multivariable linear regression yielded a CF: CACS = (1.185 × CCTAS) + (0.002 × CCTAS × attenuation threshold). When applied to CCTA data sets there was excellent correlation (
r
= 0.95;
p
< 0.0001) and agreement (mean difference −10.4 [95 % limits of agreement −258.9 to 238.1]) with traditional calcium scores. Agreement was better for calcium scores below 500; however, MESA percentile agreement was better for high risk patients. Risk stratification was excellent (Agatston groups
k
= 0.88 and MESA centiles
k
= 0.91). Eliminating the dedicated CACS scan decreased patient radiation exposure by approximately one-third.
Conclusion
CCTA calcium scores can accurately predict CACS using a simple, individualized, semiautomated approach reducing acquisition time and radiation exposure when evaluating patients for CAD. This method is not affected by the ROI location, imaging protocol, or tube voltage strengthening its clinical applicability.
Key Points
•
Coronary calcium scores can be reliably determined on contrast
-
enhanced cardiac CT
•
This score can accurately risk stratify patients
•
Elimination of a dedicated calcium scan reduces patient radiation by a third
Journal Article