Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions

Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma

Cerebellar granule neurons are the most abundant neurons in the brain, and a critical element of the circuitry that controls motor coordination and learning. In addition, granule neuron precursors (GNPs) are thought to represent cells of origin for medulloblastoma, the most common malignant brain tumor in children. Thus, understanding the signals that control the growth and differentiation of these cells has important implications for neurobiology and neuro-oncology. Our previous studies have shown that proliferation of GNPs is regulated by Sonic hedgehog (Shh), and that aberrant activation of the Shh pathway can lead to medulloblastoma. Moreover, we have demonstrated that Shh-dependent proliferation of GNPs and medulloblastoma cells can be blocked by basic fibroblast growth factor (bFGF). But while the mitogenic effects of Shh signaling have been confirmed in vivo, the inhibitory effects of bFGF have primarily been studied in culture. Here we demonstrate that mice lacking FGF signaling in GNPs exhibit no discernable changes in GNP proliferation or differentiation. In contrast, activation of FGF signaling has a potent effect on tumor growth: treatment of medulloblastoma cells with bFGF prevents them from forming tumors following transplantation, and inoculation of tumor-bearing mice with bFGF markedly inhibits tumor growth in vivo. These results suggest that activators of FGF signaling may be useful for targeting medulloblastoma and other Shh-dependent tumors

Deconstructing the effect of self-directed study on episodic memory

Self-directed learning is often associated with better long-term memory retention, however, the mechanisms that underlie this advantage remain poorly understood. This series of experiments was designed to “deconstruct” the notion of self-directed learning in order to better identify the factors most responsible for these improvements to memory. In particular, we isolate the memory advantage that comes from controlling the content of study episodes from the advantage that comes from controlling the timing of those episodes. Across four experiments, self-directed learning significantly enhanced recognition memory relative to passive observation. However, the advantage for self-directed learning was found to be present even under extremely minimal conditions of volitional control (simply pressing a button when ready to advance to the next item). Our results suggest that improvements to memory following self-directed encoding may be related to the ability to coordinate stimulus presentation with the learner’s current preparatory or attentional state, and highlight the need to consider the range of cognitive control processes involved in and influenced by self-directed study

Murine stem cell expansion steered by specific topographical microstructures

Abstract not available

Corpus Callosum Abnormalities and Their Association with Psychotic Symptoms in Patients with Schizophrenia

Background—Whilst the neuroanatomical underpinnings of the functional brain disconnectivity observed in patients with schizophrenia remain elusive, white matter fiber bundles of the brain are a likely candidate given that they represent the infrastructure for long-distance neural communication. Methods—This study investigated for diffusion abnormalities in 19 patients with chronic schizophrenia (SZ), relative to 19 matched controls, across tractography-defined segments of the Corpus Callosum. Diffusion-weighted images were acquired with 51 non-collinear gradients on a 3T scanner (1.7mm isotropic voxels). The Corpus Callosum was extracted by means of whole-brain tractography and automated fiber-clustering, and was parcellated into six segments on the basis of fiber trajectories. The diffusion indices of Fractional Anisotropy (FA) and Mode were calculated for each segment. Results—Relative to the healthy controls, the SZ patients exhibited Mode increases in the Parietal fibers, suggesting a relative absence of crossing fibers. SZ patients also exhibited FA reductions in the Frontal fibers, which were underpinned by increased in Radial Diffusivity, consistent with myelin abnormalities. Significant correlations were observed between patients' degree of Reality Distortion and their FA and Radial Diffusivity, such that the most severely psychotic patients were the least abnormal in terms of their Frontal fiber diffusivity. Conclusions—The SZ patients exhibited a variety of diffusion abnormalities in the Corpus Callosum, which were related to the severity of their psychotic symptoms. To the extent that diffusion abnormalities influence axonal transmission velocities, these results provide support for those theories that emphasize neural timing abnormalities in the etiology of schizophrenia