Little is currently known about the alterations in the topological organization of the white matter (WM) structural networks in patients with multiple sclerosis (MS). In the present study, we used diffusion tensor imaging and deterministic tractography to map the WM structural networks in 39 MS patients and 39 age- and gender-matched healthy controls. Graph theoretical methods were applied to investigate alterations in the network efficiency in these patients. The MS patients and the controls exhibited efficient small-world properties in their WM structural networks. However, the global and local network efficiencies were significantly decreased in the MS patients compared with the controls, with the most pronounced changes observed in the sensorimotor, visual, default-mode, and language areas. Furthermore, the decreased network efficiencies were significantly correlated with the expanded disability status scale scores, the disease durations, and the total WM lesion loads. Together, the results suggest a disrupted integrity in the large-scale brain systems in MS, thus providing new insights into the understanding of MS connectome. Our data also suggest that a topology-based brain network analysis can provide potential biomarkers for disease diagnosis and for monitoring the progression and treatment effects for patients with MS.
Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision-making deficit in rats with visceral hypersensitivity (VH). Now, by combining integrative neurobiological approaches, we show that ACC-reactive astrogliosis and activity-dependent impairment of lactate release occur in VH rats. Exogenous lactate supply rescues chronic-visceral-pain-caused impairments of ACC phase locking and decision making, which can be mimicked by optogenetic activation of ACC astrocytes. Large-scale electrophysiological recordings in free-moving animals during a decision-making task indicate that optogenetic astrocytic activation improves decision-making performance and engages ACC phase locking and BLA-to-ACC information flow. Collectively, these observations support the idea of an "astrocyte-neuron l-lactate shuttle" and suggest that targeting astrocytes may help with cognitive dysfunctions under chronic visceral pain.
Memory is a dynamic brain function that is continually processed after encoding. Although psychologic concepts of mental schema are now well established, they have rarely been considered in animal studies. We used a behavior paradigm of multiple flavor-place paired associates (PAs) and showed that memory schema facilitates fast acquisition of new PAs in a single trial. The hippocampus is necessary for the encoding of new PAs and for memory retrieval within a certain time window—24 h following new PA consolidation. Whereas the anterior cingulate cortex (ACC) plays a critical role for dynamic PA learning and consolidation during training sessions, ACC is essential in schema representation and activation. New myelin generation is essential for learning. Neural activity in the cortical regions impacts myelination by regulating oligodendrocyte (OL) proliferation, differentiation, and myelin formation. Here, we show that newly formed OL progenitor cells and mature OLs are increased following repeated PA learning and that establishment of the memory schema is associated with enhanced myelin strength in the ACC region. Furthermore, to ensure that myelination is necessary for the acquisition of paired-associate learning, ACC lysolecithin-induced demyelination revealed impaired PA learning associated with decrease in ACC θ band power and reduced spike-field coherence and phase-locking in ACC.—Hasan, M., Kanna, M. S., Jun, W., Ramkrishnan, A. S., Iqbal, Z., Lee, Y., Li, Y. Schema-like learning and memory consolidation acting through myelination.
Electrophysiological studies have shown the enhanced response of anterior cingulate cortex (ACC) to colorectal distension in viscerally hypersensitive (VH) rats, which can be observed up to 7 weeks following colonic anaphylaxis, independent of colon inflammation, suggesting a mechanism for learning and triggering of pain memories in the ACC neuronal circuitry. Activity-dependent plasticity in synaptic strength may serve as a key mechanism that reflects cortical plasticity. However, only a few reports have indicated the synaptic plasticity of ACC in vivo. In the present study, electrophysiological recording showed long-lasting potentiation of local field potential in the medial thalamus (MT)-ACC synapses in VH rats. Theta burst stimulation in the MT reliably induced long-term potentiation in the MT-ACC pathway in normal rats, but was occluded in the VH state. Further, repeated tetanization of MT increased ACC neuronal activity and visceral pain responses of normal rats, mimicking VH rats. In conclusion, we demonstrated for the first time that visceral hypersensitivity is associated with alterations of synaptic plasticity in the ACC. The ACC synaptic strengthening in chronic visceral pain may engage signal transduction pathways that are in common with those activated by electrical stimulation, and serves as an attractive cellular model of functional visceral pain.
Many previous studies suggested that both short-term and long-term motor training can modulate brain structures. However, little evidence exists for such brain anatomical changes in top-level gymnasts. Using diffusion-weighted and structural magnetic resonance images of the human brain, we applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) as well as FA-VBA (voxel-based analysis of fractional anisotropy, a VBM-style analysis) methods to quantitatively compare the brain structural differences between the world class gymnasts (WCG) and the non-athlete groups. In order to reduce the rate of false positive findings, we first determined that the clusters defined at a threshold of t > 2.3 and a cluster significance of p < 0.05 (FWE-corrected) across all subjects were the brain regions that showed significant differences in a between-group comparison. We then constructed several between-group comparisons based on the repeated diffusion or structural MRI data and created the intersecting regions from multiple between-group comparisons. Thus, we found significantly decreased fractional anisotropy (FA) not only in the white matter of the WCG in areas that included the bilateral superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior occipito-frontal fascicle, but also in the gray matter of the WCG in areas that included the bilateral middle cingulum, bilateral postcentral gyri, and bilateral motor regions. We also identified significantly increased gray matter density in the WCG, especially in the left inferior frontal gyrus, bilateral inferior and superior parietal lobule, bilateral superior lateral occipital cortex, left cuneus, left angular gyrus, and right postcentral gyrus. We speculate that the brain changes of the WCG may reflect the gymnasts' extraordinary ability to estimate the direction of their movements, their speed of execution, and their identification of their own and surrounding objects' locations. Our findings suggest that our method of constructing intersecting regions from multiple between-group comparison can considerably reduce the false positives, and our results provide new insights into the brain structure changes induced by long-term intensive gymnastic training.
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