A Behavioral Characterization of the Likelihood Ratio Order

It is well known that stochastic dominance is equivalent to a unanimity property for monotone expected utilities. For lotteries over a finite set of prizes, we establish an analogous relationship between likelihood ratio dominance and monotone betweenness preferences, which are an important generalization of expected utility. (JEL D11, D44)

Social Behavior and Ultrasonic Vocalizations in a Genetic Rat Model Haploinsufficient for the Cross-Disorder Risk Gene Cacna1c

The top-ranked cross-disorder risk gene CACNA1C is strongly associated with multiple neuropsychiatric dysfunctions. In a recent series of studies, we applied a genomically informed approach and contributed extensively to the behavioral characterization of a genetic rat model haploinsufficient for the cross-disorder risk gene Cacna1c. Because deficits in processing social signals are associated with reduced social functioning as commonly seen in neuropsychiatric disorders, we focused on socio-affective communication through 22-kHz and 50-kHz ultrasonic vocalizations (USV). Specifically, we applied a reciprocal approach for studying socio-affective communication in sender and receiver by including rough-and-tumble play and playback of 22-kHz and 50-kHz USV. Here, we review the findings obtained in this recent series of studies and link them to the key features of 50-kHz USV emission during rough-and-tumble play and social approach behavior evoked by playback of 22-kHz and 50-kHz USV. We conclude that Cacna1c haploinsufficiency in rats leads to robust deficits in socio-affective communication through 22-kHz and 50-kHz USV and associated alterations in social behavior, such as rough-and-tumble play behavior.

Neuropathological and behavioral characterization of aged Grn R493X progranulin-deficient frontotemporal dementia knockin mice

Frontotemporal lobar degeneration (FTLD) causes a spectrum of clinical presentations of frontotemporal dementia (FTD), including progressive changes in behavior, personality, executive function, and language. Up to 20% of familial FTLD cases are caused by progranulin (GRN) haploinsufficiency (FTD-GRN), with one of the most common causal variant being a nonsense mutation at arginine 493 (R493X). Recently, a genetic knockin FTD-GRN mouse model was generated bearing this GrnR493X mutation, at the analogous arginine in murine Grn. Aged, homozygous GrnR493X mice (GrnR493X/R493X) have been shown to phenotypically replicate several neuropathological hallmarks previously demonstrated in Grn null mice. We conducted a comprehensive neuropathological and behavioral assessment of 18 month old GrnR493X/R493X mice, observing a striking lysosomal dysfunction and thalamic neurodegeneration not previously described in this model, as well as a male-specific increase in generalized anxiety. These findings provide additional phenotypic markers of pathogenesis in aged GrnR493X/R493X mice that will contribute to better defining mechanisms underlying FTD-GRN, and offer relevant outcome measures for preclinical efficacy testing of novel therapeutics that target nonsense mutations leading to this devastating disease.

Meta-analysis of grey matter changes and their behavioral characterization in patients with alcohol use disorder

Alcohol Use Disorder (AUD) is associated with reductions in grey matter (GM) volume which can lead to changes in numerous brain functions. The results of previous studies on altered GM in AUD differ considerably in the regions identified. Three meta-analyses carried out between 2014 and 2017 yielded different results. The present study includes the considerable amount of newer research and delivers a state-of-the art meta-analysis in line with recently published guidelines. Additionally, we behaviorally characterized affected regions using fMRI metadata and identified related brain networks by determining their meta-analytic connectivity patterns. Twenty-seven studies with 1,045 AUD patients and 1,054 healthy controls were included in the analysis and analyzed by means of Anatomical Likelihood Estimation (ALE). GM alterations were identified in eight clusters covering different parts of the cingulate and medial frontal gyri, paracentral lobes, left post- and precentral gyri, left anterior and right posterior insulae and left superior frontal gyrus. The behavioral characterization associated these regions with specific cognitive, emotional, somatosensory and motor functions. Moreover, the clusters represent nodes within behaviorally relevant brain networks. Our results suggest that GM reduction in AUD could disrupt network communication responsible for the neurocognitive impairments associated with high chronic alcohol consumption.