Neural surprise in somatosensory Bayesian learning

Tracking statistical regularities of the environment is important for shaping human behavior and perception. Evidence suggests that the brain learns environmental dependencies using Bayesian principles. However, much remains unknown about the employed algorithms, for somesthesis in particular. Here, we describe the cortical dynamics of the somatosensory learning system to investigate both the form of the generative model as well as its neural surprise signatures. Specifically, we recorded EEG data from 40 participants subjected to a somatosensory roving-stimulus paradigm and performed single-trial modeling across peri-stimulus time in both sensor and source space. Our Bayesian model selection procedure indicates that evoked potentials are best described by a non-hierarchical learning model that tracks transitions between observations using leaky integration. From around 70ms post-stimulus onset, secondary somatosensory cortices are found to represent confidence-corrected surprise as a measure of model inadequacy. Indications of Bayesian surprise encoding, reflecting model updating, are found in primary somatosensory cortex from around 140ms. This dissociation is compatible with the idea that early surprise signals may control subsequent model update rates. In sum, our findings support the hypothesis that early somatosensory processing reflects Bayesian perceptual learning and contribute to an understanding of its underlying mechanisms

The gene-reduction effect of chromosomal losses detected in gastric cancers

<p>Abstract</p> <p>Background</p> <p>The level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.</p> <p>Methods</p> <p>The pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).</p> <p>Results</p> <p>Most of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).</p> <p>Conclusions</p> <p>The cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.</p

Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E- cadherin germline mutation.

E-Cadherin alterations have been reported frequently in sporadic diffuse type gastric and lobular breast carcinomas. Germline mutations of this gene have been identified recently in several gastric cancer families. We analyzed seven patients with a family history of the disease who had diffuse type gastric cancer diagnosed before the age of 45 for germline mutations in CDH1, the gene encoding the E-cadherin protein. We identified a frameshift mutation in exon 3 in one patient with a strong family history of gastric cancer. The same germline mutation was found in the patient&#39;s mother, who had metachronous development of lobular breast and diffuse type gastric carcinomas. Immunohistochemistry for E-cadherin protein expression revealed an abnormal staining pattern in both of these tumors, suggesting complete inactivation of the cell adhesion molecule. Thus, our finding suggests that besides diffuse type gastric cancer, lobular breast carcinomas may be associated with germline CDH1 mutations