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Peter Lee

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6 papers

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YNIMG Journal 2019 Journal Article

Neural substrates of cognitive reserve in Alzheimer's disease spectrum and normal aging

Dong Hyuk Lee
Peter Lee
Sang Won Seo
Jee Hoon Roh
Minyoung Oh
Jungsu S. Oh
Seung Jun Oh
Jae Seung Kim

The concept of cognitive reserve (CR) originated from discrepancies between the degree of brain pathology and the severity of clinical manifestations. CR has been characterized through CR proxies, such as education and occupation complexity; however, such approaches have inherent limitations. Although several methods have been developed to overcome these limitations, they fail to reflect the entire Alzheimer's disease (AD) pathology. Meanwhile, graph theory analysis, one of most powerful and flexible approaches, have established remarkable network properties of the brain. The functional and structural brain networks are damaged in neurodegenerative diseases. Therefore, network analysis has been applied to clarify the characteristics of the disease or give insight. Here, using multimodal neuroimaging, we propose an intuitive model to estimate CR based on its original definition, and explore the neural substrates of CR from the perspective of networks and functional connectivity. A total of 87 subjects (21 AD, 32 mild cognitive impairment, and 34 normal aging) underwent tau and amyloid PET, 3D T1-weighted MR, and resting-state fMRI. We hypothesized CR as a residual of actual cognitive performance and expected performance to be related to quantitative factors, such as AD pathology, demographics, and a genetic factor. Then, we correlated this marker using education and occupation complexity as conventional CR proxies. We validated this marker by testing whether it would modulate the effect of brain pathology on memory function. To examine the neural substrates associated with CR, we performed graph analysis to investigate the association between the CR marker and network measures at different granularities in total subjects, AD spectrum and normal aging, respectively. The CR marker from our model was well associated with education and occupation complexity. More directly, the CR marker was revealed to modify the relationship between brain pathology and memory function among AD spectrum. The CR marker was correlated with the global efficiency of the entire network, nodal clustering coefficient, and local efficiency of the right middle-temporal pole. In connectivity analysis, one cluster of edges centered on right middle-temporal pole was significantly correlated with the CR marker. In subgroup analysis, the network measures of right middle-temporal pole still correlated with the CR marker among AD spectrum. However, right precentral gyrus was revealed to be associated with the CR marker in normal aging. This study demonstrates that our intuitive model using multimodal neuroimaging and network perspective adequately and comprehensively captures CR. From a network perspective, CR is associated with the capacity to process information efficiently in the brain. The right middle-temporal pole was revealed to be a pivotal neural substrate of CR in AD spectrum. These findings foster understanding of AD and will be useful to help identify individuals with vulnerability or resistance to AD pathology, and characterize patients for intervention or drug trials.

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YNIMG Journal 2017 Journal Article

Normalization of cortical thickness measurements across different T1 magnetic resonance imaging protocols by novel W-Score standardization

Jinyong Chung
Kwangsun Yoo
Peter Lee
Chan Mi Kim
Jee Hoon Roh
Ji Eun Park
Sang Joon Kim
Sang Won Seo

Background The use of different 3D T1-weighted magnetic resonance (T1 MR) imaging protocols induces image incompatibility across multicenter studies, negating the many advantages of multicenter studies. A few methods have been developed to address this problem, but significant image incompatibility still remains. Thus, we developed a novel and convenient method to improve image compatibility. Methods W-score standardization creates quality reference values by using a healthy group to obtain normalized disease values. We developed a protocol-specific w-score standardization to control the protocol effect, which is applied to each protocol separately. We used three data sets. In dataset 1, brain T1 MR images of normal controls (NC) and patients with Alzheimer’s disease (AD) from two centers, acquired with different T1 MR protocols, were used (Protocol 1 and 2, n = 45/group). In dataset 2, data from six subjects, who underwent MRI with two different protocols (Protocol 1 and 2), were used with different repetition times, echo times, and slice thicknesses. In dataset 3, T1 MR images from a large number of healthy normal controls (Protocol 1: n = 148, Protocol 2: n = 343) were collected for w-score standardization. The protocol effect and disease effect on subjects' cortical thickness were analyzed before and after the application of protocol-specific w-score standardization. Results As expected, different protocols resulted in differing cortical thickness measurements in both NC and AD subjects. Different measurements were obtained for the same subject when imaged with different protocols. Multivariate pattern difference between measurements was observed between the protocols. Classification accuracy between two protocols was nearly 90%. After applying protocol-specific w-score standardization, the differences between the protocols substantially decreased. Most importantly, protocol-specific w-score standardization reduced both univariate and multivariate differences in the images while maintaining the AD disease effect. Compared to conventional regression methods, our method showed the best performance for in terms of controlling the protocol effect while preserving disease information. Conclusions Protocol-specific w-score standardization effectively resolved the concerns of conventional regression methods. It showed the best performance for improving the compatibility of a T1 MR post-processed feature, cortical thickness.

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AAAI Conference 2016 Conference Paper

An Online Logic Programming Development Environment

Christian Reotutar
Mbathio Diagne
Evgenii Balai
Edward Wertz
Peter Lee
Shao-Lon Yeh
Yuanlin Zhang

Recent progress in logic programming, particularly answer set programming, has enabled us to teach it to undergraduate and high school students. We developed an online answer set programming environment with simple interface and self contained ﬁle system. It is expected to make the teaching of answer set programming more effective and help us to reach more students.

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TAAS Journal 2011 Journal Article

Detecting Locally Distributed Predicates

Michael De Rosa
Seth Copen Goldstein
Peter Lee
Jason Campbell
Padmanabhan S. Pillai

In this article, we formalize locally distributed predicates, a concept previously introduced to address specific challenges associated with modular robotics and distributed debugging. A locally distributed predicate (LDP) is a novel construction for representing and detecting distributed properties in sparse-topology systems. Our previous work on LDPs presented empirical validation; here we show a formal model for two variants of the LDP algorithm, LDP-Basic and LDP-Snapshot, and establish performance bounds for these variants. We prove that LDP-Basic can detect strong stable predicates, that LDP-Snapshot can detect all stable predicates, and discuss their applicability to various distributed programming domains and to spatial computing in general. LDP detection in bounded-degree networks is shown to be scale-free, making the approach particularly attractive for specific topologies, even though LDPs are less efficient than snapshot algorithms in general distributed systems.

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TCS Journal 2003 Journal Article

Automated techniques for provably safe mobile code

Christopher Colby
Karl Crary
Robert Harper
Peter Lee
Frank Pfenning

We present a general framework for provably safe mobile code. It relies on a formal definition of a safety policy and explicit evidence for compliance with this policy which is attached to a binary. Concrete realizations of this framework are proof-carrying code, where the evidence for safety is a formal proof generated by a certifying compiler, and typed assembly language, where the evidence for safety is given via type annotations propagated throughout the compilation process in typed intermediate languages. Validity of the evidence is established via a small trusted type checker, either directly on the binary or indirectly on proof representations in a logical framework.

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TCS Journal 1991 Journal Article

Metacircularity in the polymorphic λ-calculus

Frank Pfenning
Peter Lee

We consider the question of whether a useful notion of metacircularity exists for the polymorphic λ-calculus. Even though complete metacircularity seems to be impossible, we obtain a close approximation to a metacircular interpreter. We begin by presenting an encoding for the Girard-Reynolds second-order polymorphic λ-calculus in the third-order polymorphic λ-calculus. The encoding makes use of representations in which abstractions are represented by abstractions, thus eliminating the need for the explicit representation of environments. We then extend this construction to encompass all of the ω-order polymorphic λ-calculus (F ω). The representation has the property that evaluation is definable, and furthermore that only well-typed terms can be represented and thus type inference does not have to be explicitly defined. Unfortunately, this metacircularity result seems to fall short of providing a useful framework for typed metaprogramming. We speculate on the reasons for this failure and the prospects for overcoming it in the future. In addition, we briefly describe our efforts in designing a practical programming language based on F ω.

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