The Effect of Shape Familiarity on Object-Based Attention

Thesis advisor: Sean MacEvoyHumans can pay attention both to particular locations in space (“space-based attention”) and to specific objects (“object-based attention”). The goal of this study was to understand the role of object familiarity and complexity in the control of object-based attention. We used a well-known manifestation of object-based attention known as same-object advantage (SOA) to test this. In SOA, participants are faster at detecting a target event that takes place in a cued object than one that takes place in an uncued object, even when the distance between cue and target is kept fixed. To control shape familiarity, objects in the current study were randomly-generated irregular polygons known as Attneave shapes. Experiment 1 showed that SOA exists for these irregular shapes, even when participants are unfamiliar with them. In Experiment 2, participants first underwent training designed to familiarize them with a subset of the Attneave shapes used in Experiment 1. Again there was a significant SOA. If object-based attention is dependent upon object familiarity, we hypothesized that SOA, measured in terms of reaction time, should be greater in Experiment 2 than Experiment 1. Although there was a numerical increase in the reaction time signature of SOA in Experiment 2, this effect was not significant. While this does not strictly support our hypothesis, several aspects of this study suggest that object familiarity does play some role in mediating object-based attention.Thesis (BS) — Boston College, 2013.Submitted to: Boston College. College of Arts and Sciences.Discipline: Psychology Honors Program.Discipline: Psychology

Rates of β-amyloid deposition indicate widespread simultaneous accumulation throughout the brain

Amyloid plaque aggregation is a pathologic hallmark of Alzheimer's disease (AD) that occurs early in the disease. However, little is known about its progression throughout the brain. Using Pittsburgh Compound B (PIB)-PET imaging, we investigated the progression of regional amyloid accumulation in cognitively normal older adults. We found that all examined regions reached their peak accumulation rates 24-28 years after an estimated initiation corresponding to the mean baseline PIB-PET signal in amyloid-negative older adults. We also investigated the effect of increased genetic risk conferred by the apolipoprotein-E ɛ4 allele on rates of amyloid accumulation, as well as the relationship between regional amyloid accumulation and regional tau pathology, another hallmark of AD, measured with Flortaucipir-PET. Carriers of the ɛ4 allele had faster amyloid accumulation in all brain regions. Furthermore, in all regions excluding the temporal lobe, faster amyloid accumulation was associated with greater tau burden. These results indicate that amyloid accumulates near-simultaneously throughout the brain and is associated with higher AD pathology, and that genetic risk of AD is associated with faster amyloid accumulation

Tau accumulation in clinically normal older adults is associated with hippocampal hyperactivity.

Animal studies demonstrate that hyperactive neurons facilitate early accumulation and spread of tau and amyloid-β proteins in the pathological cascade of Alzheimer's disease (AD). Human neuroimaging studies have linked hippocampal hyperactivity to amyloid-β accumulation, apolipoprotein ε4 (APOE4) and clinical progression from prodromal AD to clinical dementia. The relationship between hippocampal hyperactivity and early AD molecular pathology (amyloid-β and tau accumulation) prior to clinical symptoms remains to be elucidated. Here, we studied 120 clinically normal older humans (80 females/40 males) enrolled in the Harvard Aging Brain Study. We measured functional magnetic resonance imaging (fMRI) activity during successful memory encoding and amyloid-β accumulation with PiB-PET imaging. Additionally, we measured tau accumulation using AV1451 PET imaging in a subset of 87 participants. In this subset, we found that inferior temporal tau accumulation was associated with increased fMRI activity in the hippocampus, but showed no clear association with amyloid. Together, the findings support a hypothetical model of the evolution of preclinical AD that place hippocampal hyperactivity concurrent with spread of tau pathology to neocortical regions prior to clinical impairment.The circumstances under which the hippocampus becomes hyperactive in preclinical stages of Alzheimer's disease (AD) have thus far remained elusive. Recent advances in positron emission tomography (PET) tracers now enable in-vivo characterization of amyloid-β and tau accumulation. Here, we combine amyloid and tau PET with functional magnetic resonance imaging (fMRI) to examine the association between Alzheimer's disease pathology and memory-related brain activity in clinically normal older adults. We found an association between increased hippocampal activity and tau accumulation in the inferior temporal cortex. These data suggest that the pathogenesis of hippocampal hyperactivity occurs concurrent with the spread of tau pathology from the entorhinal cortex to the neocortex, prior to the clinical manifestations of Alzheimer's disease

Interactive versus additive relationships between regional cortical thinning and amyloid burden in predicting clinical decline in mild AD and MCI individuals

The biological mechanisms that link Beta-amyloid (Aβ) plaque deposition, neurodegeneration, and clinical decline in Alzheimer's disease (AD) dementia, have not been completely elucidated. Here we studied whether amyloid accumulation and neurodegeneration, independently or interactively, predict clinical decline over time in a group of memory impaired older individuals [diagnosed with either amnestic mild cognitive impairment (MCI), or mild AD dementia]. We found that baseline Aβ-associated cortical thinning across clusters encompassing lateral and medial temporal and parietal cortices was related to higher baseline Clinical Dementia Rating Sum-of-Boxes (CDR-SB). Baseline Aβ-associated cortical thinning also predicted CDR-SB over time. Notably, the association between CDR-SB change and cortical thickness values from the right lateral temporo-parietal cortex and right precuneus was driven by individuals with high Aβ burden. In contrast, the association between cortical thickness in the medial temporal lobe (MTL) and clinical decline was similar for individuals with high or low Aβ burden. Furthermore, amyloid pathology was a stronger predictor for clinical decline than MTL thickness. While this study validates previous findings relating AD biomarkers of neurodegeneration to clinical impairment, here we show that regions outside the MTL may be more vulnerable and specific to AD dementia. Additionally, excluding mild AD individuals revealed that these relationships remained, suggesting that lower cortical thickness values in specific regions, vulnerable to amyloid pathology, predict clinical decline already at the prodromal stage

PET staging of amyloidosis using striatum

Amyloid PET data are commonly expressed as binary measures of cortical deposition. However, not all individuals with high cortical amyloid will experience rapid cognitive decline. Motivated by postmortem data, we evaluated a three-stage PET classification: low cortical; high cortical, low striatal; and high cortical, high striatal amyloid; hypothesizing this model could better reflect Alzheimer's dementia progression than a model based only on cortical measures. We classified PET data from 1433 participants (646 normal, 574 mild cognitive impairment, and 213 AD), explored the successive involvement of cortex and striatum using 3-year follow-up PET data, and evaluated the associations between PET stages, hippocampal volumes, and cognition. Follow-up data indicated that PET detects amyloid first in cortex and then in striatum. Our three-category staging including striatum better predicted hippocampal volumes and subsequent cognition than a three-category staging including only cortical amyloid. PET can evaluate amyloid expansion from cortex to subcortex. Using striatal signal as a marker of advanced amyloidosis may increase predictive power in Alzheimer's dementia research