Dwelling Quietly in the Rich Club: Brain Network Determinants of Slow Cortical Fluctuations

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously -- elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala, and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow time scales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding "feeder" cortical regions show unstable, rapidly fluctuating dynamics likely crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics.Comment: 35 pages, 6 figure

A part-task trainer for underwater tether awareness

Thesis (S.B. and M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1998.Includes bibliographical references (p. 43).by Jonathan L. Zalesky.S.B.and M.Eng

Estimating the impact of structural directionality: How reliable are undirected connectomes?

Directionality is a fundamental feature of network connections. Most structural brain networks are intrinsically directed because of the nature of chemical synapses, which comprise most neuronal connections. Due to limitations of non-invasive imaging techniques, the directionality of connections between structurally connected regions of the human brain cannot be confirmed. Hence, connections are represented as undirected, and it is still unknown how this lack of directionality affects brain network topology. Using six directed brain networks from different species and parcellations (cat, mouse, C. elegans, and three macaque networks), we estimate the inaccuracies in network measures (degree, betweenness, clustering coefficient, path length, global efficiency, participation index, and small worldness) associated with the removal of the directionality of connections. We employ three different methods to render directed brain networks undirected: (i) remove uni-directional connections, (ii) add reciprocal connections, and (iii) combine equal numbers of removed and added uni-directional connections. We quantify the extent of inaccuracy in network measures introduced through neglecting connection directionality for individual nodes and across the network. We find that the coarse division between core and peripheral nodes remains accurate for undirected networks. However, hub nodes differ considerably when directionality is neglected. Comparing the different methods to generate undirected networks from directed ones, we generally find that the addition of reciprocal connections (false positives) causes larger errors in graph-theoretic measures than the removal of the same number of directed connections (false negatives). These findings suggest that directionality plays an essential role in shaping brain networks and highlight some limitations of undirected connectomes.Comment: 29 pages, 6 figures, 9 supplementary figures, 4 supplementary table

Genetic and epigenetic regulation in Lingo-1 : Effects on cognitive function and white matter microstructure in a case-control study for schizophrenia

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3′-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016–1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology

Endocrine Mechanisms of Puberty in Heifers: Estradiol Negative Feedback Regulation of Luteinizing Hormone Secretion

The hypothesis that luteinizing hormone (LH) secretion in prepubertal females is responsive to estradiol negative feedback and that decreased feedback occurs as puberty approaches was tested in heifers. In the first experiment, seven heifers were maintained prepubertal by dietary energy restriction until 508 days of age (Day 0). All heifers were placed on a high-energy diet on Day 0 at which time they received no additional treatment (CONT), were ovariectomized (OVX) or were ovariectomized and subcutaneously implanted with estradiol-17β (OVX-E2). This feeding regimen was used to synchronize reproductive state in all heifers. A second experiment was performed with 16 prepubertal heifers using the same treatments at 266 days (Day 0) of age (CONT, OVX and OVX-E2) but no dietary intake manipulation. In both experiments, LH secretion increased rapidly following ovariectomy in OVX heifers. In the initial experiment, LH secretion was maintained at a low level in OVX-E2 heifers until a synchronous rapid increase was noted coincidental with puberty in the CONT heifer. In the second experiment, LH secretion increased gradually in OVX-E2 heifers and attained castrate levels coincidental with puberty in CONT heifers. A gradual increase in LH secretion occurred as puberty approached in CONT heifers. These results indicate that: a) LH secretion in prepubertal heifers is responsive to estradiol negative feedback; and b) estradiol negative feedback decreases during the prepubertal period in beef heifers

Effects of MGA on Prepubertal Crossbred Beef Heifers

A study was conducted using 55 prepubertal replacement crossbred beef heifers to determine the effect of feeding MGA to prepubertal heifers on age at puberty. No difference (P= .65) was detected between MGA treated heifers versus control heifers for age at puberty. There was no difference (P= .80) in age at conception to A1 for the two groups

Effects of MGA on Prepubertal Beef Heifers

A 2-year study (1 995 and 1996) utilized prepubertal beef heifers to study the effects of feeding MGA to induce puberty. Heifers were allotted to two groups, control or treatment, based on breed, age and weight. Treatment heifers received MGA for 14 days at a rate of .4 mglday with their diet, while control heifers received the same diet free of MGA. In year 1 (n = 55; control = 28, treatment = 27), heifers averaged 627.7 Ib and were 301.9 days of age at the start of the treatment. There was no difference in age at puberty (P=.65) with control heifers 378.5 rt8.3 days of age and treatment heifers 373.0rt8.5 days of age. Forty-seven of 55 heifers became pregnant during the breeding season (85.5%). Of the 47 heifers, 37 heifers gave birth to a live calf (78.7%). In year 2 (control =20, treatment = 21 ), heifers averaged 609.0 Ib and were 300.4 days of age at the start of the treatment. Control heifers were 373.6 ± 7.3 days of age and treatment heifers 382.4rt7.3 days of age at puberty (P= .40). Thirty-eight of 41 heifers became pregnant during the breeding season (92.7%). Thirty-five of 41 heifers were bred Al (85.4%). Thirteen of 16 control heifers and 12 of 19 treatment heifers became pregnant to Al (P\u3e.50). The use of MGA to induce puberty has potential, but further research is needed to determine the age at which it should be administered

South Dakota Retained Ownership Demonstration

Three hundred seventy-four calves representing 44 cow-calf producers were consigned to a custom feedlot. Steer calves (254 head) consigned in October weighed 522 Ib initially, gained 2.91 1b per head daily, and averaged 1,100 Ib at slaughter after an average of 200 days on feed. Average cost of gain and profitability were $48.94 per cwt and -$12.03 per head, respectively. Steers consigned in January weighed 71 1 Ib initially, gained 3.07 Ib per head daily, and averaged 1,135 1b at slaughter after 141 days on feed. Average cost of gain and profitability were $43.59 per cwt and -$64.22 per head, respectively. Losses observed for 1994-95 were due to low carcass beef prices relative to the price of feeder cattle in fall of 1994 and January of 1995. As in previous years, average daily gain, days on feed, and quality grade appear related to differences in profit between cattle