A simple permutation‐based test of intermodal correspondence

Many key findings in neuroimaging studies involve similarities between brain maps, but statistical methods used to measure these findings have varied. Current state‐of‐the‐art methods involve comparing observed group‐level brain maps (after averaging intensities at each image location across multiple subjects) against spatial null models of these group‐level maps. However, these methods typically make strong and potentially unrealistic statistical assumptions, such as covariance stationarity. To address these issues, in this article we propose using subject‐level data and a classical permutation testing framework to test and assess similarities between brain maps. Our method is comparable to traditional permutation tests in that it involves randomly permuting subjects to generate a null distribution of intermodal correspondence statistics, which we compare to an observed statistic to estimate a p‐value. We apply and compare our method in simulated and real neuroimaging data from the Philadelphia Neurodevelopmental Cohort. We show that our method performs well for detecting relationships between modalities known to be strongly related (cortical thickness and sulcal depth), and it is conservative when an association would not be expected (cortical thickness and activation on the n‐back working memory task). Notably, our method is the most flexible and reliable for localizing intermodal relationships within subregions of the brain and allows for generalizable statistical inference.     

Long‐term follow‐up of patients with asymptomatic occlusion of the internal carotid artery with good and impaired cerebral vasomotor reactivity

Background: Cerebral hemodynamic status might be prognostic for either the symptomatic or asymptomatic course of carotid occlusive disease. It is determined by evaluating cerebral vasomotor reactivity (VMR). We assessed VMR in asymptomatic patients with total occlusion of the internal carotid artery (ICA) and followed them to evaluate the role of impaired VMR in predicting ischaemic stroke (IS). Methods: Thirty‐five patients (21 men, mean age ± SD 68 ± 7.5 years) with unilateral asymptomatic ICA occlusion were studied by transcranial Doppler and the Diamox test (intravenous 1.0 g acetazolamide) and followed for 48 months or until reaching the end‐points of IS, transient ischaemic attack, or vascular death. VMR% was evaluated by recording the percent differences in peak systolic blood flow velocities in each middle cerebral artery at baseline and after Diamox administration. Results: Based on VMR% calculations, 14 (40%) patients had good VMRs and 21 (60%) had impaired VMRs. The global annual risk of ipsilateral ischaemic events was 5.7%. The annual ipsilateral ischaemic event risk was 1.8% in patients with good VMRs, whilst it was 7.1% in patients with impaired VMRs. An impaired VMR was significantly correlated with ipsilateral IS (Kaplan–Meier log rank statistic, P = 0.04). Conclusions: Our results support the value of VMR assessment for identifying asymptomatic patients with carotid occlusion who belong to a high‐risk subgroup for IS. New trials using extracranial‐to‐intracranial bypass surgery in patients with asymptomatic ICA occlusion and impaired VMRs are warranted.     

Effects of daytime naps on procedural and declarative memory in patients with schizophrenia

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Straight memory deficits and sleep disturbances are well-known in patients with schizophrenia. This study tested the hypothesis that patients with schizophrenia have a deficit in procedural and declarative memory consolidation after a short midday nap when compared to healthy controls and patients with remitted to moderate major depression.Following a normal night’s sleep, 22 healthy subjects, 20 patients with major depression and 21 patients with schizophrenia were studied in a napping and wake condition in a random-order cross-over design, early in the afternoon. To test declarative memory, the Rey-Osterrieth Complex Figure Test respectively the Taylor Complex Figure Test and, for procedural learning, a mirror tracing task were performed.The present study is the first to demonstrate significant differences between individuals with schizophrenia, depression and healthy matched controls with regard to measures of sleep and memory performance after a short period of daytime sleep (napping). In particular we found that a daytime nap of only about 40 min led to improvement of declarative memory performance in all investigated groups, whereas no beneficial effect was seen on procedural performance in the group of medicated patients with schizophrenia in contrast to healthy controls and patients with remitted to moderate major depression.     

Fronto‐temporal dysregulation in asymptomatic bipolar I patients: A paired associate functional MRI study

Bipolar disorder is associated with persistent declarative memory disturbances, but the neural basis of these deficits is not well understood. We used fMRI to investigate brain activity during performance on a face‐name paired associate task, which allows for the dissociation of encoding and recall‐related memory processes. Fifteen clinically remitted bipolar I disorder patients and 24 demographically matched healthy comparison subjects were scanned during task performance. At the voxel level, bipolar patients showed reduced cortical activation, relative to controls, in multiple task‐related brain regions during encoding. During recognition, bipolar patients under‐activated left hippocampal and parahippocampal regions, despite adequate task performance. Region of interest analyses indicated that, during encoding, bipolar patients had greater bilateral dorsolateral prefrontal (DLPFC) activity than healthy subjects. In contrast, during recognition patients showed hypo‐activation relative to controls in the right, but not the left, DLPFC. Although hippocampal activity did not differ between groups during encoding, bipolar patients failed to activate hippocampal regions to the same extent as healthy subjects during recognition. Finally, while better task performance was associated with recognition‐related hippocampal activity in healthy subjects, bipolar patients showed an inverse relationship between task performance and hippocampal activity. Remitted bipolar patients over‐engaged dorsolateral prefrontal regions when learning face‐name pairs, but relative hypoactivation in both prefrontal and medial temporal regions during recognition. These findings suggest a neural basis for the long‐term memory deficits consistently observed in patients with bipolar disorder; further, as these patterns appear in symptomatically remitted patients, they are unlikely to be an artifact of mood symptoms. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Auditory Oddball fMRI in Schizophrenia: Association of Negative Symptoms with Regional Hypoactivation to Novel Distractors

Schizophrenia is associated with abnormal processing of salient stimuli, which may contribute to clinical symptoms. We used fMRI and a standard auditory three-stimulus task to examine attention processing. Target stimuli and novel distractors were presented to 17 patients and 21 healthy controls and activation was correlated with negative and positive symptoms. To targets, patients overactivated multiple regions including premotor cortex, anterior cingulate, temporal cortex, insula, and hippocampus, and also showed attenuated deactivation within occipital cortex. To distractors, patients overactivated left ventrolateral prefrontal cortex. This overactivation may reflect hypersensitivity to salient stimuli in schizophrenia. Patients also exhibited an inverse correlation between negative symptom severity and activation to novel distractors in the dorsolateral prefrontal cortex, premotor area, and ventral striatum. Novelty-induced activity within prefrontal cortex and ventral striatum may represent a useful intermediate phenotype for studies of negative symptoms.     

Comparison of the Heritability of Schizophrenia and Endophenotypes in the COGS-1 Family Study

Background:

Twin and multiplex family studies have established significant heritability for schizophrenia (SZ), often summarized as 81%. The Consortium on the Genetics of Schizophrenia (COGS-1) family study was designed to deconstruct the genetic architecture of SZ using neurocognitive and neurophysiological endophenotypes, for which heritability estimates ranged from 18% to 50% (mean = 30%). This study assessed the heritability of SZ in these families to determine whether there is a “heritability gap” between the diagnosis and related endophenotypes.

Methods:

Nuclear families (N = 296) with a SZ proband, an unaffected sibling, and both parents (n = 1366 subjects; mean family size = 4.6) underwent comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives of interviewed subjects (N = 3304 subjects; mean family size = 11.2). Heritability estimates of psychotic disorders were computed for both nuclear and extended families.

Results:

The heritability of SZ was 31% and 44% for nuclear and extended families. The inclusion of bipolar disorder increased the heritability to 37% for the nuclear families. When major depression was added, heritability estimates dropped to 34% and 20% for nuclear and extended families, respectively.

Conclusions:

Endophenotypes and psychotic disorders exhibit comparable levels of heritability in the COGS-1 family sample. The ascertainment of families with discordant sibpairs to increase endophenotypic contrast may underestimate diagnostic heritability relative to other studies. However, population-based studies also report significantly lower heritability estimates for SZ. Collectively, these findings support the importance of endophenotype-based strategies and the dimensional view of psychosis.Key words: schizophrenia, psychosis, endophenotypes, cognition, biomarkers, heritability     

Are Dermatophytid Reactions in Patients with Kerion Celsi Much More Common Than Previously Thought? A Prospective Study

Dermatophytid reactions are secondary eruptions in response to dermatophytosis. Only a few cases demonstrating an association between dermatophytid reactions and tinea capitis have been reported. Dermatophytid reactions were evaluated in patients diagnosed with kerion celsi. Patients admitted to the dermatology clinic of Van Regional Training and Research Hospital between November 22, 2012, and July 1, 2013, diagnosed with kerion celsi were evaluated for dermatophytid reactions. Six girls (32%) and 13 boys (68%) were included in this study. Dermatophytid reactions were detected in 13 of the 19 patients (68%). Seven patients (36.84%) had eczematous patches or plaques and three (15.8%) had papules. Eczematous lesions, papules, and pustules were noted in two patients (10.5%) and one (5.3%) had signs of an angioedema‐like reaction. Dermatophytid reactions in all patients were observed before the initiation of therapy. According to our clinical experiences, dermatophytid reactions in patients with kerion celsi were more common than reported. Eczematous scaly patches or plaques were the most frequently seen forms of dermatophytid in patients with kerion celsi. Dermatophytid reactions may occur before or after initiation of systemic antifungal therapy. Recognition of this reaction is important so that dermatophytids can be distinguished from drug reactions and the decision can be made whether to continue or to stop the systemic antifungal treatment.     

Risk factors for breast cancer-related upper extremity lymphedema: Is immediate autologous breast reconstruction one of them?

Breast cancer related upper extremity lymphedema (BCRL) reduces the quality of life of those who have had surgery for breast cancer. The aim of this study is to evaluate the risk factors for BCRL and determine whether immediate autologous tissue breast reconstruction is one of them. A case control study was conducted comparing patients with BCRL (n=97) to surgically treated breast cancer patients without BCRL (control, n=126). The groups were matched for age, type of breast surgery and radiation therapy. Postoperative upper extremity infection, body mass index (BMI), occupation (level of hand-use), and immediate autologous tissue breast reconstruction were investigated as a risk factor of BCRL. Mastectomy was performed on 47.6 % (n=60) and 37.2% (n=36) of patients in the control and the BCRL groups, respectively. Eight patients (13.3%) had immediate autologous tissue breast reconstruction in the control mastectomy group. Six of 36 BCRL patients (16.7%) underwent mastectomy with immediate autologous tissue breast reconstruction. There was no significant difference between groups with respect to incidence or method of immediate reconstruction (p=0.65). Patient occupation (level of hand use) was found to be positively correlated to development of BCRL (p=0.0001). Upper extremity infection rate was 22.7% in the BCRL group and 4.0% in the controls (p=0.0001). The mean BMI in the control and BCRL groups 26.8 kg/m² and 29.1kg/m², respectively (p=0.003). In conclusion, in this study characteristics positively associated with development of BCRL included occupation, infection, and increased BMI. Immediate reconstruction of the breast was not found as a risk factor for BCRL. However larger studies are needed, to further evaluate the effect of breast reconstruction on BCRL.     

Anti-hyperglycemic and antigenotoxic potential of Ulva rigida ethanolic extract in the experimental diabetes mellitus

An increased reactive oxygen species (ROS) and insufficient antioxidant activity is known in diabetes mellitus (DM). Antioxidant compounds in the human foods or supplementary diets can be used to counteract several diseases. The analysis of micronuclei (MN) is a cytogenetic technique used to show chromosomal damage caused by clastogenic affects. The present study was designed to evaluate: (i) the effects of diabetes mellitus on bone marrow MN frequency, (ii) the effect of oral administration of Ulva rigida ethanolic extract (URE) on MN frequency produced by DM, and (iii) some hematological values in normal and streptozotocin-induced diabetic rats. Daily fluid and food consumptions, weekly body weights, blood glucose concentrations and serum insulin levels were also examined in the study groups during the two different administration periods. The blood glucose concentration and MN frequency have been significantly increased in diabetic rats compared with the normal rats (p < 0.0001). Especially, URE-30d group treatment in diabetic rats was significantly decreased blood glucose concentrations and MN frequency. This is the first report on the anti-hyperglycemic, anti-oxidative and genotoxic/antigenotoxic capacity of U. rigida in vivo. Our results suggest that URE shows strong anti-hyperglycemic and antigenotoxic effect on the genotoxicity produced by DM in rats.