Apolipoprotein E and familial longevity

Exceptional longevity is associated with substantial heritability. The ?4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ?2 allele with decreased mortality, although inconsistently. Offspring from long-lived families and spouse controls were recruited at 3 sites in the United States and Denmark. We used generalized estimating equations to compare the likelihood of carrying risk alleles in offspring (n = 2307) and spouse controls (n = 764), adjusting for age, sex, level of education, and family membership. The likelihood of carrying an APOE ?4 allele or a G allele in rs2075650 was lower (odds ratio [OR], 0.75; p = 0.005 and OR, 0.70; p = 0.002) and the likelihood of carrying an APOE ?2 allele was higher (OR, 1.5; p = 0.007) among family members in the offspring generation than among their spouse controls. Our findings support the hypothesis that both reduction in the frequency of the ?4 allele and increase in the frequency of the ?2 allele contribute to longevity.     

Surprise: Unexpected Action Execution and Unexpected Inhibition Recruit the Same Fronto-Basal-Ganglia Network

Unexpected and thus surprising events are omnipresent and oftentimes require adaptive behavior such as unexpected inhibition or unexpected action. The current theory of unexpected events suggests that such unexpected events just like global stopping recruit a fronto-basal-ganglia network. A global suppressive effect impacting ongoing motor responses and cognition is specifically attributed to the subthalamic nucleus (STN). Previous studies either used separate tasks or presented unexpected, task-unrelated stimuli during response inhibition tasks to relate the neural signature of unexpected events to that of stopping. Here, we aimed to test these predictions using a within task design with identical stimulus material for both unexpected action and unexpected inhibition using functional magnetic resonance imaging (fMRI) for the first time. To this end, 32 healthy human participants of both sexes performed a cue-informed go/nogo task comprising expected and unexpected action and inhibition trials during fMRI. Using conjunction, contrast, and Bayesian analyses, we demonstrate that unexpected action elicited by an unexpected go signal and unexpected inhibition elicited by an unexpected nogo signal recruited the same fronto-basal-ganglia network which is usually assigned to stopping. Furthermore, the stronger the unexpected action-related activity in the STN region was the more detrimental was the effect on response times. The present results thus complement earlier findings and provide direct evidence for the unified theory of unexpected events while ruling out alternative task and novelty effects.SIGNIFICANCE STATEMENT This is the first study using functional magnetic resonance imaging (fMRI) to test whether unexpected events regardless of whether they require unexpected action or inhibition recruit a fronto-basal-ganglia network just like stopping. In contrast to previous studies, we used identical stimulus material for both conditions within one task. This enabled us to directly test predictions of the current theory of unexpected events and, moreover, to test for condition-specific neural signatures. The present results underpin that both processes recruit the same neural network while excluding alternative task and novelty effects. The simple task design thus provides an avenue to studying surprise as a pure form of reactive inhibition in neuropsychiatric patients displaying inhibitory deficits who often have a limited testing capacity.     

Responses to Heartbeats in Ventromedial Prefrontal Cortex Contribute to Subjective Preference-Based Decisions

Forrest Gump or The Matrix? Preference-based decisions are subjective and entail self-reflection. However, these self-related features are unaccounted for by known neural mechanisms of valuation and choice. Self-related processes have been linked to a basic interoceptive biological mechanism, the neural monitoring of heartbeats, in particular in ventromedial prefrontal cortex (vmPFC), a region also involved in value encoding. We thus hypothesized a functional coupling between the neural monitoring of heartbeats and the precision of value encoding in vmPFC. Human participants of both sexes were presented with pairs of movie titles. They indicated either which movie they preferred or performed a control objective visual discrimination that did not require self-reflection. Using magnetoencephalography, we measured heartbeat-evoked responses (HERs) before option presentation and confirmed that HERs in vmPFC were larger when preparing for the subjective, self-related task. We retrieved the expected cortical value network during choice with time-resolved statistical modeling. Crucially, we show that larger HERs before option presentation are followed by stronger value encoding during choice in vmPFC. This effect is independent of overall vmPFC baseline activity. The neural interaction between HERs and value encoding predicted preference-based choice consistency over time, accounting for both interindividual differences and trial-to-trial fluctuations within individuals. Neither cardiac activity nor arousal fluctuations could account for any of the effects. HERs did not interact with the encoding of perceptual evidence in the discrimination task. Our results show that the self-reflection underlying preference-based decisions involves HERs, and that HER integration to subjective value encoding in vmPFC contributes to preference stability.SIGNIFICANCE STATEMENT Deciding whether you prefer Forrest Gump or The Matrix is based on subjective values, which only you, the decision-maker, can estimate and compare, by asking yourself. Yet, how self-reflection is biologically implemented and its contribution to subjective valuation are not known. We show that in ventromedial prefrontal cortex, the neural response to heartbeats, an interoceptive self-related process, influences the cortical representation of subjective value. The neural interaction between the cortical monitoring of heartbeats and value encoding predicts choice consistency (i.e., whether you consistently prefer Forrest Gump over Matrix over time. Our results pave the way for the quantification of self-related processes in decision-making and may shed new light on the relationship between maladaptive decisions and impaired interoception.     

Objectively characterizing Huntington’s disease using a novel upper limb dexterity test

Journal of Neurology - The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent...