Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory.The structures that are important for encoding and storage of novel information have been the focus of extensive research since the pioneering work of Scoville, Milner, and Penfield (1-4). A convergence of research in animals and humans has led to the hypothesis that the hippocampus and related medial temporal lobe structures are critical for the encoding of novel information for subsequent storage in the neocortex (2, 5-7). In humans, anterograde amnesia-the inability to learn new information-is associated with bilateral lesions of medial temporal lobe structures (2,8). In nonhuman primates, singleunit recordings have identified neurons that respond preferentially to novel or familiar stimuli. These neurons are found in structures that receive output from the hippocampus [such as the anterior thalamus (9) and nucleus accumbens (10)] and in structures that provide afferent input to the hippocampus [such as the entorhinal cortex (11)]. Lesion studies in animals have provided extensive data on the role of medial temporal lobe structures in the performance of behavioral tasks requiring storage of novel information. For example, lesions of hippocampus and adjacent cortical structures, such as the perirhinal and entorhinal cortices, impair performance on delayed nonmatching to sample tasks in nonhuman primates (12) and rats (13). Controversies remain about the exact structures that are most important for the performance of explicit memory tasks (12-16).Functional brain imaging studies have attempted to demonstrate the role of the hippocampus and related medial temporal lobe structures in the encoding and retrieval of long-term memories in the intact human brain. Several studies using positron emission tomography have shown no evidence of a medial temporal lobe contribution to encoding and recognition (17-19); however, more recent reports have shown changes in the hippocampus in re...

Understanding the pathogenesis of cancer-related bone disease is crucial to the discovery of new therapies. Here we identify activin A, a TGF-β family member, as a therapeutically amenable target exploited by multiple myeloma (MM) to alter its microenvironmental niche favoring osteolysis. Increased bone marrow plasma activin A levels were found in MM patients with osteolytic disease. MM cell engagement of marrow stromal cells enhanced activin A secretion via adhesion-mediated JNK activation. Activin A, in turn, inhibited osteoblast differentiation via SMAD2-dependent distalless homeobox-5 down-regulation. Targeting activin A by a soluble decoy receptor reversed osteoblast inhibition, ameliorated MM bone disease, and inhibited tumor growth in an in vivo humanized MM model, setting the stage for testing in human clinical trials.osteoblasts | osteoclasts | tumor niche

There is a lack of physiological data pertaining to how listening humans process auditory information. Functional magnetic resonance imaging (fMRI) has provided some data for the auditory cortex in awake humans, but there is still a paucity of comparable data for subcortical auditory areas where the early stages of processing take place, as amply demonstrated by single-unit studies in animals. It is unclear why fMRI has been unsuccessful in imaging auditory brain-stem activity, but one problem may be cardiac-related, pulsatile brain-stem motion. To examine this, a method eliminating such motion (using cardiac gating) was applied to map sound-related activity in the auditory cortices and inferior colliculi in the brain stem. Activation in both the colliculi and cortex became more discernible when gating was used. In contrast with the cortex, the improvement in the colliculi resulted from a reduction in signal variability, rather than from an increase in percent signal change. This reduction is consistent with the hypothesis that motion or pulsatile flow is a major factor in brain-stem imaging. The way now seems clear to studying activity throughout the human auditory pathway in listening humans.