The effect of apolipoprotein E genotype on spatial processing in humans: A meta-analysis and systematic review.

The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the lifespan is unclear. One cognitive domain that is affected early in the course of Alzheimer's disease is spatial cognition, yet the evidence for APOE-related changes in spatial cognition is mixed. In this meta-analysis we assessed the impact of carrying the APOE4 allele on five subdomains of spatial cognition across the lifespan. We included studies of healthy human participants where an APOE4-carrier group (heterozygous or homozygous) could be compared to a homozygous group of APOE3-carriers. We identified 156 studies in total from three databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review. APOE4 carriers scored significantly lower than APOE3 carriers (θˆ = -.08 [-.14, -.02]) on tests of spatial long-term memory; this effect was very small and was not modulated by age. On other subdomains of spatial cognition (spatial construction, spatial working memory, spatial reasoning, navigation) there were no effects of genotype. Overall, our results demonstrate that the APOE4 allele exerts little influence on spatial cognitive abilities in healthy adults.

Retrograde amnesia abolishes the self-reference effect in anterograde memory.

Is retrograde amnesia associated with an ability to know who we are and imagine what we will be like in the future? To answer this question, we had S.G., a patient with focal retrograde amnesia following hypoxia, two brain-damaged (control) patients with no retrograde memory deficits, and healthy controls judge whether each of a series of trait adjectives was descriptive of their present self, future self, another person, and that person in the future, and later recognize studied traits among distractors. Healthy controls and control patients were more accurate in recognizing self-related compared to other-related traits, a phenomenon known as the self-reference effect (SRE). This held for both present and future self-views. By contrast, no evidence of (present or future) SRE was observed in SG, who concomitantly showed reduced certainty about his personality traits. These findings indicate that retrograde amnesia can weaken the self-schema and preclude its instantiation during self-related processing.

The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice.

Intertemporal choices require trade-offs between short-term and long-term outcomes. Ventromedial prefrontal cortex (vmPFC) damage causes steep discounting of future rewards (delay discounting [DD]) and impoverished episodic future thinking (EFT). The role of vmPFC in reward valuation, EFT, and their interaction during intertemporal choice is still unclear. Here, 12 patients with lesions to vmPFC and 41 healthy controls chose between smaller-immediate and larger-delayed hypothetical monetary rewards while we manipulated reward magnitude and the availability of EFT cues. In the EFT condition, participants imagined personal events to occur at the delays associated with the larger-delayed rewards. We found that DD was steeper in vmPFC patients compared to controls, and not modulated by reward magnitude. However, EFT cues downregulated DD in vmPFC patients as well as controls. These findings indicate that vmPFC integrity is critical for the valuation of (future) rewards, but not to instill EFT in intertemporal choice.

Social media usage reveals recovery of small businesses after natural hazard events.

The challenge of nowcasting the effect of natural hazard events (e.g., earthquakes, floods, hurricanes) on assets, people and society is of primary importance for assessing the ability of such systems to recover from extreme events. Traditional recovery estimates, such as surveys and interviews, are usually costly, time consuming and do not scale. Here we present a methodology to indirectly estimate the post-emergency recovery status (downtime) of small businesses in urban areas looking at their online posting activity on social media. Analysing the time series of posts before and after an event, we quantify the downtime of small businesses for three natural hazard events occurred in Nepal, Puerto Rico and Mexico. A convenient and reliable method for nowcasting the post-emergency recovery status of economic activities could help local governments and decision makers to better target their interventions and distribute the available resources more effectively.

Scene processing following damage to the ventromedial prefrontal cortex.

It has been suggested that the mental construction of scene imagery is a core process underpinning functions such as autobiographical memory, future thinking and spatial navigation. Damage to the ventromedial prefrontal cortex in humans can cause deficits in all of these cognitive domains. Moreover, it has also been reported that patients with ventromedial prefrontal cortex lesions are impaired at imagining fictitious scenes, although they seem able to describe specific scenes from autobiographical events. In general, not much is known about how ventromedial prefrontal cortex patients process scenes. Here, we deployed a recently-developed task to provide insights into this issue, which involved detecting either semantic (e.g. an elephant with butterflies for ears) or constructive (e.g. an endless staircase) violations in scene images. Identifying constructive violations typically provokes the formation of internal scene models in healthy control participants. We tested patients with bilateral ventromedial prefrontal cortex damage, brain-damaged control patients and healthy control participants. We found no evidence for statistically significant differences between the groups in detecting either type of violation. These results suggest that an intact ventromedial prefrontal cortex is not necessary for some aspects of scene processing, with implications for understanding its role in functions such as autobiographical memory and future thinking.

Functional connectivity along the anterior-posterior axis of hippocampal subfields in the ageing human brain.

While age-related volumetric changes in human hippocampal subfields have been reported, little is known about patterns of subfield functional connectivity (FC) in the context of healthy ageing. Here we investigated age-related changes in patterns of FC down the anterior-posterior axis of each subfield. Using high resolution structural MRI we delineated the dentate gyrus (DG), CA fields (including separating DG from CA3), the subiculum, pre/parasubiculum, and the uncus in healthy young and older adults. We then used high resolution resting state functional MRI to measure FC in each group and to directly compare them. We first examined the FC of each subfield in its entirety, in terms of FC with other subfields and with neighboring cortical regions, namely, entorhinal, perirhinal, posterior parahippocampal, and retrosplenial cortices. Next, we analyzed subfield to subfield FC within different portions along the hippocampal anterior-posterior axis, and FC of each subfield portion with the neighboring cortical regions of interest. In general, the FC of the older adults was similar to that observed in the younger adults. We found that, as in the young group, the older group displayed intrinsic FC between the subfields that aligned with the tri-synaptic circuit but also extended beyond it, and that FC between the subfields and neighboring cortical areas differed markedly along the anterior-posterior axis of each subfield. We observed only one significant difference between the young and older groups. Compared to the young group, the older participants had significantly reduced FC between the anterior CA1-subiculum transition region and the transentorhinal cortex, two brain regions known to be disproportionately affected during the early stages of age-related tau accumulation. Overall, these results contribute to ongoing efforts to characterize human hippocampal subfield connectivity, with implications for understanding hippocampal function and its modulation in the ageing brain.

Boundary extension is attenuated in patients with ventromedial prefrontal cortex damage.

The ventromedial prefrontal cortex (vmPFC) and hippocampus have been implicated in the mental construction of scenes and events. However, little is known about their specific contributions to these cognitive functions. Boundary extension (BE) is a robust indicator of fast, automatic, and implicit scene construction. BE occurs when individuals who are viewing scenes automatically imagine what might be beyond the view, and consequently later misremember having seen a greater expanse of the scene. Patients with hippocampal damage show attenuated BE because of their scene construction impairment. In the current study, we administered BE tasks to patients with vmPFC damage, brain-damaged control patients, and healthy control participants. We also contrasted the performance of these patients to the previously-published data from patients with hippocampal lesions (Mullally, Intraub, & Maguire, 2012). We found that vmPFC-damaged patients showed reduced BE compared to brain-damaged and healthy controls. Indeed, BE attenuation was similar following vmPFC or hippocampal damage. Notably, however, whereas hippocampal damage seems to particularly impair the spatial coherence of scenes, vmPFC damage leads to a difficulty constructing scenes in a broader sense, with the prediction of what should be in a scene, and the monitoring or integration of the scene elements being particularly compromised. We conclude that vmPFC and hippocampus play important and complementary roles in scene construction.

Episodic future thinking and future-based decision-making in a case of retrograde amnesia.

We investigated episodic future thinking (EFT) and future-based cognition and decision-making in patient SG, who developed a dense retrograde amnesia following hypoxia due to a cardiac arrest. Despite intact general cognitive and executive functioning, SG was unable to remember events from his entire lifetime. He had, however, relatively spared anterograde memory and general semantic knowledge. Voxel-based morphometry detected a reduction of gray matter in the thalamus, cerebellum and fusiform gyrus bilaterally, and, at a reduced threshold, in several regions of the autobiographical memory network, including the hippocampi. We show that SG is unable to imagine personal future events, but can imagine fictitious events not self-relevant and not located in subjective time. Despite severely impaired EFT, SG shows normal attitudes towards the future time, and normal delay discounting rates. These findings suggest that retrieval of autobiographical information from long-term memory is necessary for EFT. However, relatively spared anterograde memory and general semantic knowledge may be sufficient to allow construction of fictitious experiences. As well, EFT is not necessary to drive future-oriented cognition and choice. These findings highlight the relation between autobiographical memory and EFT, and the fractionation of human temporal consciousness. Moreover, they contribute to our understanding of retrograde amnesia as an impairment of memory as well as future thinking.

Comparing and Contrasting the Cognitive Effects of Hippocampal and Ventromedial Prefrontal Cortex Damage: A Review of Human Lesion Studies.

The hippocampus and ventromedial prefrontal cortex (vmPFC) are closely connected brain regions whose functions are still debated. In order to offer a fresh perspective on understanding the contributions of these two brain regions to cognition, in this review we considered cognitive tasks that usually elicit deficits in hippocampal-damaged patients (e.g., autobiographical memory retrieval), and examined the performance of vmPFC-lesioned patients on these tasks. We then took cognitive tasks where performance is typically compromised following vmPFC damage (e.g., decision making), and looked at how these are affected by hippocampal lesions. Three salient motifs emerged. First, there are surprising gaps in our knowledge about how hippocampal and vmPFC patients perform on tasks typically associated with the other group. Second, while hippocampal or vmPFC damage seems to adversely affect performance on so-called hippocampal tasks, the performance of hippocampal and vmPFC patients clearly diverges on classic vmPFC tasks. Third, although performance appears analogous on hippocampal tasks, on closer inspection, there are significant disparities between hippocampal and vmPFC patients. Based on these findings, we suggest a tentative hierarchical model to explain the functions of the hippocampus and vmPFC. We propose that the vmPFC initiates the construction of mental scenes by coordinating the curation of relevant elements from neocortical areas, which are then funneled into the hippocampus to build a scene. The vmPFC then engages in iterative re-initiation via feedback loops with neocortex and hippocampus to facilitate the flow and integration of the multiple scenes that comprise the coherent unfolding of an extended mental event.

Episodic future thinking following vmPFC damage: Impaired event construction, maintenance, or narration?

OBJECTIVE: Functional neuroimaging and lesion studies show that the ventromedial prefrontal cortex (vmPFC) is implicated in episodic future thinking (EFT), yet its role remains unclear. In this study, we sought to (a) confirm recent findings of impaired EFT in patients with lesions to the vmPFC (vmPFC patients) using a new task, and (b) investigate the influence of nonepisodic mechanisms, namely, narrative construction and working memory maintenance, on vmPFC patients' EFT performance. METHOD: vmPFC patients and healthy participants imagined future events using pictures as cues, described pictures, or described pictures while maintaining them in working memory after an observation phase. RESULTS: Compared with the controls, vmPFC patients produced less specific reports across all conditions, as indicated by fewer internal (episodic) but a similar number of external (semantic) details. However, controlling for description and working memory performance did not eliminate group differences in EFT. Moreover, vmPFC damage reduced the proportion of internal-to-total details for EFT only. CONCLUSIONS: These results indicate that EFT problems in vmPFC patients are not merely the reflection of problems in maintaining in working memory and narrating events, but, more likely, of an impairment upstream, in creating novel events. (PsycINFO Database Record