Test-retest reliability of FreeSurfer automated hippocampal subfield segmentation within and across scanners

The human hippocampus is vulnerable to a range of degenerative conditions and as such, accurate in vivo measurement of the hippocampus and hippocampal substructures via neuroimaging is of great interest for understanding mechanisms of disease as well as for use as a biomarker in clinical trials of novel therapeutics. Although total hippocampal volume can be measured relatively reliably, it is critical to understand how this reliability is affected by acquisition on different scanners, as multiple scanning platforms would likely be utilized in large-scale clinical trials. This is particularly true for hippocampal subregional measurements, which have only relatively recently been measurable through common image processing platforms such as FreeSurfer. Accurate segmentation of these subregions is challenging due to their small size, magnetic resonance imaging (MRI) signal loss in medial temporal regions of the brain, and lack of contrast for delineation from standard neuroimaging procedures. Here, we assess the test-retest reliability of the FreeSurfer automated hippocampal subfield segmentation procedure using two Siemens model scanners (a Siemens Trio and Prismafit Trio upgrade). T1-weighted images were acquired for 11 generally healthy younger participants (two scans on the Trio and one scan on the Prismafit). Each scan was processed through the standard cross-sectional stream and the recently released longitudinal pipeline in FreeSurfer v6.0 for hippocampal segmentation. Test-retest reliability of the volumetric measures was examined for individual subfields as well as percent volume difference and Dice overlap among scans and intra-class correlation coefficients (ICC). Reliability was high in the molecular layer, dentate gyrus, and whole hippocampus with the inclusion of three time points with mean volume differences among scans less than 3%, overlap greater than 80%, and ICC >0.95. The parasubiculum and hippocampal fissure showed the least improvement in reliability with mean volume difference greater than 5%, overlap less than 70%, and ICC scores ranging from 0.78 to 0.89. Other subregions, including the CA regions, were stable in their mean volume difference and overlap (75% respectively) and showed improvement in reliability with the inclusion of three scans (ICC ​> ​0.9). Reliability was generally higher within scanner (Trio-Trio), however, Trio-Prismafit reliability was also high and did not exhibit an obvious bias. These results suggest that the FreeSurfer automated segmentation procedure is a reliable method to measure total as well as hippocampal subregional volumes and may be useful in clinical applications including as an endpoint for future clinical trials of conditions affecting the hippocampus

Rapidly Measuring the Speed of Unconscious Learning: Amnesics Learn Quickly and Happy People Slowly

BACKGROUND We introduce a method for quickly determining the rate of implicit learning. METHODOLOGY/PRINCIPAL FINDINGS The task involves making a binary prediction for a probabilistic sequence over 10 minutes; from this it is possible to determine the influence of events of a different number of trials in the past on the current decision. This profile directly reflects the learning rate parameter of a large class of learning algorithms including the delta and Rescorla-Wagner rules. To illustrate the use of the method, we compare a person with amnesia with normal controls and we compare people with induced happy and sad moods. CONCLUSIONS/SIGNIFICANCE Learning on the task is likely both associative and implicit. We argue theoretically and demonstrate empirically that both amnesia and also transient negative moods can be associated with an especially large learning rate: People with amnesia can learn quickly and happy people slowl

Prefrontal cortex output circuits guide reward seeking through divergent cue encoding

The prefrontal cortex is a critical neuroanatomical hub for controlling motivated behaviours across mammalian species. In addition to intra-cortical connectivity, prefrontal projection neurons innervate subcortical structures that contribute to reward-seeking behaviours, such as the ventral striatum and midline thalamus. While connectivity among these structures contributes to appetitive behaviours, how projection-specific prefrontal neurons encode reward-relevant information to guide reward seeking is unknown. Here we use in vivo two-photon calcium imaging to monitor the activity of dorsomedial prefrontal neurons in mice during an appetitive Pavlovian conditioning task. At the population level, these neurons display diverse activity patterns during the presentation of reward-predictive cues. However, recordings from prefrontal neurons with resolved projection targets reveal that individual corticostriatal neurons show response tuning to reward-predictive cues, such that excitatory cue responses are amplified across learning. By contrast, corticothalamic neurons gradually develop new, primarily inhibitory responses to reward-predictive cues across learning. Furthermore, bidirectional optogenetic manipulation of these neurons reveals that stimulation of corticostriatal neurons promotes conditioned reward-seeking behaviour after learning, while activity in corticothalamic neurons suppresses both the acquisition and expression of conditioned reward seeking. These data show how prefrontal circuitry can dynamically control reward-seeking behaviour through the opposing activities of projection-specific cell populations

Hereditary angioedema in women

<p>Abstract</p> <p>Women with hereditary angioedema (HAE) are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,....) play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women). C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.</p

A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction

Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor expression in the mPFC-NAc pathway promotes the addiction-like phenotype. Our study unravels a new neurobiological mechanism underlying resilience and vulnerability to the development of food addiction, which could pave the way towards novel and efficient interventions for this disorder.This work was supported by the Spanish Ministerio de Economía y Competitividad-MINECO (#SAF2017-84060-R-AEI/FEDER-UE), the Spanish Instituto de Salud Carlos III, RETICS-RTA (#RD12/0028/0023), the Generalitat de Catalunya, AGAUR (#2017 SGR-669), ICREA-Acadèmia (#2015) and the Spanish Ministerio de Sanidad, Servicios Sociales e Igualdad, Plan Nacional Sobre Drogas (#PNSD-2017I068) to R.M., Fundació La Marató-TV3 (#2016/20-30) to E.M-G., the German Research Foundation (#CRC1193 “Neurobiology of Resilience”, TP A05 and B04) to B.L. and S.G., and the Boehringer Ingelheim Foundation to B.L., S.G. and I.R.A. The work of M.N.A was supported by the Emergent AI Center funded by the Carl-Zeiss-Stiftung. NARSAD Young Investigator Award (#22434), MINECO Ramón y Cajal (#RYC- 2014-15784) and (#SAF2016-76565-R) and Fondo Europeo de Desarrollo Regional (FEDER) to R.A. DIUE Generalitat de Catalunya (#2017 SGR 595), MINECO (#SAF2016-79956-R), EU (#Era Net Neuron PCIN-2013-060), Fundació La Marató-TV3 (#2016/20-31), CRG acknowledges support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Center of Excellence Severo Ochoa (#SEV-2012-0208), the CERCA Programme/Generalitat de Catalunya, the CIBER of Rare Diseases of the ISCIII to M.D. MINECO Ramón y Cajal (#RYC-2016-20414), AGAUR (#2017 SGR 926), (#RTI2018-094887-B-I00) and Fondo Europeo de Desarrollo Regional (FEDER) to M.N