An Iterative Jackknife Approach for Assessing Reliability and Power of fMRI Group Analyses

For functional magnetic resonance imaging (fMRI) group activation maps, so-called second-level random effect approaches are commonly used, which are intended to be generalizable to the population as a whole. However, reliability of a certain activation focus as a function of group composition or group size cannot directly be deduced from such maps. This question is of particular relevance when examining smaller groups (<20–27 subjects). The approach presented here tries to address this issue by iteratively excluding each subject from a group study and presenting the overlap of the resulting (reduced) second-level maps in a group percent overlap map. This allows to judge where activation is reliable even upon excluding one, two, or three (or more) subjects, thereby also demonstrating the inherent variability that is still present in second-level analyses. Moreover, when progressively decreasing group size, foci of activation will become smaller and/or disappear; hence, the group size at which a given activation disappears can be considered to reflect the power necessary to detect this particular activation. Systematically exploiting this effect allows to rank clusters according to their observable effect size. The approach is tested using different scenarios from a recent fMRI study (children performing a “dual-use” fMRI task, n = 39), and the implications of this approach are discussed

On the critical, morally-driven, self-reflective, agents of change and transformation: A literature review on culturally competent leadership in higher education.

Cultural competence philosophy and praxis was born out of healthcare provision in the 1980s. As such, the essence of care cannot be separated from cultural competence practice

Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1.

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans. To explore this hypothesis further, we generated mice mutant at the Dixdc1 locus and analyzed their behavior. Dixdc1(-/-) mice had normal prepulse inhibition, but displayed decreased spontaneous locomotor activity, abnormal behavior in the elevated plus maze and deficits in startle reactivity. Our results suggest that Dixdc1(-/-) mice will be a useful tool to elucidate molecular pathophysiology involving Disc1 in major mental illnesses

Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers

Mouse embryos bearing hypomorphic and conditional null Fgf8 mutations have small and abnormally patterned telencephalons. We provide evidence that the hypoplasia results from decreased Foxg1 expression, reduced cell proliferation and increased cell death. In addition, alterations in the expression of Bmp4, Wnt8b, Nkx2.1 and Shh are associated with abnormal development of dorsal and ventral structures. Furthermore, nonlinear effects of Fgf8 gene dose on the expression of a subset of genes, including Bmp4 and Msx1, correlate with a holoprosencephaly phenotype and with the nonlinear expression of transcription factors that regulate neocortical patterning. These data suggest that Fgf8 functions to coordinate multiple patterning centers, and that modi. cations in the relative strength of FGF signaling can have profound effects on the relative size and nature of telencephalic subdivisions

Blood–brain barrier permeability for ammonia in patients with different grades of liver fibrosis is not different from healthy controls

Increased blood-brain barrier (BBB) permeability for ammonia is considered to be an integral part of the pathophysiology of hepatic encephalopathy (HE) in patients with liver cirrhosis. Increased glutamate-/glutamine-signal intensity in magnetic resonance spectroscopic studies of the brain in cirrhotic patients was explained as a consequence of increased cerebral ammonia uptake. As similar spectroscopic alterations are present in patients with liver fibrosis, we hypothesized that BBB permeability for ammonia is already increased in liver fibrosis, and thereby contributing to the development of HE. To test this hypothesis, cerebral perfusion and ammonia metabolism were examined through positron emission tomography with 15O-water, respectively, 13N-ammonia in patients with Ishak grades 2 and 4 fibrosis, cirrhosis, and healthy controls. There were neither global nor regional differences of cerebral blood flow, the rate constant of unidirectional transport of ammonia from blood into brain tissue, the permeability surface area product of the BBB for ammonia, the net metabolic clearance rate constant of ammonia from blood into glutamine in brain, or the metabolic rate of ammonia. The hypothesis that increased permeability of the BBB for ammonia in patients with liver fibrosis contributes to the later development of HE could not be supported by this study