Intraobserver and interobserver agreement for results of low-field magnetic resonance imaging in dogs with and without clinical signs of disk-associated wobbler syndrome

OBJECTIVE: To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer. RESULTS: There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.

Inter-observer agreement for spectral- and time-domain optical coherence tomography image grading: a prospective study

The purpose of this study was to compare inter-observer agreement of Stratus™ OCT versus Spectralis™ OCT image grading in patients with neovascular age-related macular degeneration (AMD). Thirty eyes with neovascular AMD were examined with Stratus™ OCT and Spectralis™ OCT. Four different scan protocols were used for imaging. Three observers graded the images for the presence of various pathologies. Inter-observer agreement between OCT models was assessed by calculating intra-class correlation coefficients (ICC). In Stratus™ OCT highest interobserver agreement was found for subretinal fluid (ICC: 0.79), and in Spectralis™ OCT for intraretinal cysts (IRC) (ICC: 0.93). Spectralis™ OCT showed superior interobserver agreement for IRC and epiretinal membranes (ERM) (ICC(Stratus™): for IRC 0.61; for ERM 0.56; ICC(Spectralis™): for IRC 0.93; for ERM 0.84). Increased image resolution of Spectralis™ OCT did improve the inter-observer agreement for grading intraretinal cysts and epiretinal membranes but not for other retinal changes.

Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment

Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.

Auditory verbal hallucinations: imaging, analysis, and intervention

In this article, we will link neuroimaging, data analysis, and intervention methods in an important psychiatric condition: auditory verbal hallucinations (AVH). The clinical and phenomenological background as well as neurophysiological findings will be covered and discussed with respect to noninvasive brain stimulation. Additionally, methods of noninvasive brain stimulation will be presented as ways to intervene with AVH. Finally, preliminary conclusions and possible future perspectives will be proposed.

Is gamma band EEG synchronization reduced during auditory driving in schizophrenia patients with auditory verbal hallucinations?

Auditory verbal hallucinations (AVH) in schizophrenia patients assumingly result from a state inadequate activation of the primary auditory system. We tested brain responsiveness to auditory stimulation in healthy controls (n=26), and in schizophrenia patients that frequently (n=18) or never (n=11) experienced AVH. Responsiveness was assessed by driving the EEG with click-tones at 20, 30 and 40Hz. We compared stimulus induced EEG changes between groups using spectral amplitude maps and a global measure of phase-locking (GFS). As expected, the 40Hz stimulation elicited the strongest changes. However, while controls and non-hallucinators increased 40Hz EEG activity during stimulation, a left-lateralized decrease was observed in the hallucinators. These differences were significant (p=.02). As expected, GFS increased during stimulation in controls (p=.08) and non-hallucinating patients (p=.06), which was significant when combining the two groups (p=.01). In contrast, GFS decreased with stimulation in hallucinating patients (p=0.13), resulting in a significantly different GFS response when comparing subjects with and without AVH (p<.01). Our data suggests that normally, 40Hz stimulation leads to the activation of a synchronized network representing the sensory input, but in hallucinating patients, the same stimulation partly disrupts ongoing activity in this network.

Good agreement between capillary and venous sampling for lectin pathway proteins

Background: The lectin pathway of complement activation, in particular mannose-binding lectin (MBL), has been extensively investigated over recent years. So far, studies were exclusively based on venous samples. The aim of this study was to investigate whether measurements of lectin pathway proteins obtained by capillary sampling are in agreement with venous samples. Methods: Prospective study including 31 infants that were admitted with suspected early-onset sepsis. Lectin pathway proteins were measured in simultaneously obtained capillary and venous samples. Bland–Altman plots of logarithmized results were constructed, and the mean capillary to venous ratios (ratiocap/ven) were calculated with their 95% confidence intervals (CI). Results: The agreement between capillary and venous sampling was very high for MBL (mean ratiocap/ven, 1.01; 95% CI, 0.85–1.19). Similarly, high agreement was observed for H-ficolin (mean ratiocap/ven, 1.02; 95% CI, 0.72–1.44), MASP-2 (1.04; 0.59–1.84), MASP-3 (0.96; 0.71–1.28), and MAp44 (1.01; 0.82–1.25), while the agreement was moderate for M-ficolin (mean ratiocap/ven, 0.78; 95% CI, 0.27–2.28). Conclusions: The results of this study show an excellent agreement between capillary and venous samples for most lectin pathway proteins. Except for M-ficolin, small volume capillary samples can thus be used when assessing lectin pathway proteins in neonates and young children.

The spatiotemporal pattern of auditory cortical responses during verbal hallucinations

Functional magnetic resonance imaging (fMRI) studies can provide insight into the neural correlates of hallucinations. Commonly, such studies require self-reports about the timing of the hallucination events. While many studies have found activity in higher-order sensory cortical areas, only a few have demonstrated activity of the primary auditory cortex during auditory verbal hallucinations. In this case, using self-reports as a model of brain activity may not be sensitive enough to capture all neurophysiological signals related to hallucinations. We used spatial independent component analysis (sICA) to extract the activity patterns associated with auditory verbal hallucinations in six schizophrenia patients. SICA decomposes the functional data set into a set of spatial maps without the use of any input function. The resulting activity patterns from auditory and sensorimotor components were further analyzed in a single-subject fashion using a visualization tool that allows for easy inspection of the variability of regional brain responses. We found bilateral auditory cortex activity, including Heschl's gyrus, during hallucinations of one patient, and unilateral auditory cortex activity in two more patients. The associated time courses showed a large variability in the shape, amplitude, and time of onset relative to the self-reports. However, the average of the time courses during hallucinations showed a clear association with this clinical phenomenon. We suggest that detection of this activity may be facilitated by examining hallucination epochs of sufficient length, in combination with a data-driven approach.

Differential effect of side of temporal lobe epilepsy on lateralization of hippocampal, temporolateral, and inferior frontal activation patterns during a verbal episodic memory task

The encoding of verbal stimuli elicits left-lateralized activation patterns within the medial temporal lobes in healthy adults. In our study, patients with left- and right-sided temporal lobe epilepsy (LTLE, RTLE) were investigated during the encoding and retrieval of word-pair associates using functional magnetic resonance imaging. Functional asymmetry of activation patterns in hippocampal, inferior frontal, and temporolateral neocortical areas associated with language functions was analyzed. Hippocampal activation patterns in patients with LTLE were more right-lateralized than those in patients with RTLE (P<0.05). There were no group differences with respect to lateralization in frontal or temporolateral regions of interest (ROIs). For both groups, frontal cortical activation patterns were significantly more left-lateralized than hippocampal patterns (P<0.05). For patients with LTLE, there was a strong trend toward a difference in functional asymmetry between the temporolateral and hippocampal ROIs (P=0.059). A graded effect of epileptic activity on laterality of the different regional activation patterns is discussed.

Hippocampal functional connectivity reflects verbal episodic memory network integrity

Using functional magnetic resonance imaging during a verbal memory task, we investigated correlations of signal fluctuations within the hippocampus and ipsilateral frontal as well as temporal areas in temporal lobe epilepsy patients. Declarative memory abilities were additionally examined before and after temporal lobe epilepsy surgery. A significant difference exists in functional connectivity between patients whose mnemonic functions deteriorated and those who remained stable or improved. Univariate analyses showed significantly higher preoperative coupling between the hippocampus and Brodmann area 22 for the group that decreased in verbal learning. We suggest greater coupling to reflect higher functional network integrity. Postoperatively reduced learning ability in patients with higher preoperative coupling underlines the importance of hippocampal interaction with cortical areas for successful memory formation.

Agreement between HbA1c measured by DCA 2000 and by HPLC: effects of fetal hemoglobin concentrations

In subjects with type 1 diabetes, persisting elevations of fetal hemoglobin (HbF) have been demonstrated. This study evaluated whether HbF levels typically seen in type 1 diabetes (up to 3%) interfere with glycohemoglobin determinations using a common immunologic method (DCA 2000).