Opposite Gradient Research Articles

Compressed cerebro-cerebellar functional gradients in children and adolescents with attention-deficit/hyperactivity disorder.

Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.

Global Ecology and Geography of Gender Equality.

Proximal socio-economic drivers of gender equality tend to obscure its remote ecological origins. General systems theory predicts that the greater annual variability in daylength, temperature, and daily precipitation at higher latitudes requires greater psychosocial flexibility. We extend this prediction to gender equality as a likely consequence. Accordingly, for 87 pre-industrial societies after 1500 CE, we find more gender equality in more variable habitats, and that this link is mediated by greater subsistence flexibility-foraging rather than raising plants and animals. Mutatis mutandis, these ecological predictors of global gender equality replicate in 175 modern countries after 2000 CE. Gender equality was, and still is, lowest around the Equator, higher toward the North and South Poles, and invariant in east-west direction. The geographical positioning of gender equality in pre-industrial times can predict over 40% of the opposite north-south gradients of gender equality in the opposite Northern and Southern Hemispheres today.

Significant Midlatitude Bubble‐Like Ionospheric Super‐Depletion Structure (BLISS) and Dynamic Variation of Storm‐Enhanced Density Plume During the 23 April 2023 Geomagnetic Storm

AbstractThis paper investigates the midlatitude ionospheric disturbances over the American/Atlantic longitude sector during an intense geomagnetic storm on 23 April 2023. The study utilized a combination of ground‐based observations (Global Navigation Satellite System total electron content and ionosonde) along with measurements from multiple satellite missions (GOLD, Swarm, Defense Meteorological Satellite Program, and TIMED/GUVI) to analyze storm‐time electrodynamics and neutral dynamics. We found that the storm main phase was characterized by distinct midlatitude ionospheric density gradient structures as follows: (a) In the European‐Atlantic longitude sector, a significant midlatitude bubble‐like ionospheric super‐depletion structure (BLISS) was observed after sunset. This BLISS appeared as a low‐density channel extending poleward/westward and reached ∼40° geomagnetic latitude, corresponding to an APEX height of ∼5,000 km. (b) Coincident with the BLISS, a dynamic storm‐enhanced density plume rapidly formed and decayed at local afternoon in the North American sector, with the plume intensity being doubled and halved in just a few hours. (c) The simultaneous occurrence of these strong yet opposite midlatitude gradient structures could be mainly attributed to common key drivers of prompt penetration electric fields and subauroral polarization stream electric fields. This shed light on the important role of storm‐time electrodynamic processes in shaping global ionospheric disturbances.

Comparison and Synthesis of Precipitation Data from CloudSat CPR and GPM KaPR

Employing different bands of radar to detect precipitation information in identical regions enables the acquisition of a more comprehensive precipitation cloud structure, thereby refining the continuity and completeness of precipitation measurements. This study first compared the coincident data from CloudSat W-band cloud profiling radar (CPR) and Global Precipitation Measurement Mission (GPM) Ka-band precipitation radar (KaPR) from 2014 to 2017, and then a synthesis of the radar reflectivity from CPR and KaPR was attempted to obtain a complete cloud and precipitation structure. The findings of the reflectivity comparisons indicated that the echo-top height identified by CPR is on average 3.6 to 4.2 km higher than that from KaPR, due to the higher sensitivity. Because of strong attenuation of CPR by liquid-phase particles, the reflectivity below the height of the melting layer usually shows an opposite gradient to KaPR with decreasing altitude. The difference in the near-surface rain rates of CPR and KaPR was found to be related to reflectivity gradients in the vertical direction, and the larger the reflectivity gradients, the greater the differences in near-surface rain rates. For better representing the complete vertical structure of precipitation clouds and improving the consistency of the reflectivity and precipitation rate, the radar reflectivity was weighted, synthesized from CPR and KaPR based on the gradient difference of the reflectivity from the two radars. We presented the synthesis results for a stratiform cloud and a deep convective case, and Spearman’s rank correlation coefficient (rs) between the GPM combined radiometer precipitation rate and the radar reflectivity was utilized to analyze the performance of the synthesis. The consistency between synthesized reflectivity and precipitation rate in the non-liquid phase was improved compared with KaPR, and the rs of the ice and mixed phases was increased by about 12% and 10%, respectively.

Observational Evidence of the Vertical Exchange of Ozone within the Urban Planetary Boundary Layer in Shanghai, China

The vertical mass exchange of ozone (O3) plays an important role in determining surface O3 air quality, the understanding of which, however, is greatly limited by the lack of continuous measurements in the vertical direction. Here, we characterize O3 variations at a high-altitude monitoring site at the top of Shanghai Tower (SHT) and discuss the potential impacts of the vertical exchange of air pollutants on O3 air quality within the urban planetary boundary layer (PBL) based on continuous measurements during 2017–2018. During the daytime, two distinct patterns of vertical O3 gradient are detected. In summer, the daytime O3 formation at SHT is observed to be more limited by nitrogen oxides (NOx) than the surface, which, together with the efficient vertical mixings, results in higher O3 levels in the upper mixing layer. In cold months, the opposite vertical gradient is observed, which is associated with weak vertical exchange and NOx-saturated O3 formation. A nighttime O3 reservoir layer and consistent morning O3 entrainments are detected all year round. These results provide direct evidence of the vertical mixings within the urban PBL, underscoring the pressing need for improving vertical resolution in near-surface layers of air quality models.

Effects of gradient structures of cathode catalyst layers on performance and durability of proton exchange membrane fuel cells

Improving performance and durability of proton exchange membrane fuel cells (PEMFC) is crucial for promoting commercial applications. Deep understanding of the underlying degradation mechanisms is still lacking. In this study, a two-way coupling performance-degradation model is established by incorporating one-dimensional (1D) Platinum (Pt) degradation model into 1D PEMFC performance model, which can predict Pt degradation phenomenon considering Pt dissolution, Pt2+ diffusion and reprecipitation in cathode catalyst layers (CCLs) and resulting performance loss. Effects of gradient CCL structures in terms of ionomer weight, Pt loading and Pt particle size on degradation and performance are investigated. The results show that multi-layer CCLs with more ionomer, more Pt loading, and/or smaller particles near membrane have higher performance, while the opposite gradients present enhanced anti-degradation capacity. Wave-like spatial distributions of Pt mass retention are observed in gradient CCLs, with significant difference across the sub-layer interface. Combined effects of two gradient distributions are also investigated. It is found that for performance, simply add-up roles are followed, namely combining two gradient distributions with higher performance can obtain higher performance, and vice versa. For durability, synergy effects are identified, in which two gradient structures with opposite final Pt mass distribution have competitive influence on Pt2+ local transport, with local Pt2+ diffusion suppressed, the catalyst distribution uniformity improved and performance loss alleviated. The gradient CCL structure considering the balance of performance and durability is identified based on 28 structures studied. Such add-up roles for performance and synergy effects for durability provide new insights for improving the design of PEMFCs.

Perception-Distortion Balanced Super-Resolution: A Multi-Objective Optimization Perspective.

High perceptual quality and low distortion degree are two important goals in image restoration tasks such as super-resolution (SR). Most of the existing SR methods aim to achieve these goals by minimizing the corresponding yet conflicting losses, such as the l1 loss and the adversarial loss. Unfortunately, the commonly used gradient-based optimizers, such as Adam, are hard to balance these objectives due to the opposite gradient decent directions of the contradictory losses. In this paper, we formulate the perception-distortion trade-off in SR as a multi-objective optimization problem and develop a new optimizer by integrating the gradient-free evolutionary algorithm (EA) with gradient-based Adam, where EA and Adam focus on the divergence and convergence of the optimization directions respectively. As a result, a population of optimal models with different perception-distortion preferences is obtained. We then design a fusion network to merge these models into a single stronger one for an effective perception-distortion trade-off. Experiments demonstrate that with the same backbone network, the perception-distortion balanced SR model trained by our method can achieve better perceptual quality than its competitors while attaining better reconstruction fidelity. Codes and models can be found at https://github.com/csslc/EA-Adam.

Preliminary experimental data analysis for Digital Twin development of a large bore Dual-Fuel engine

In recent years, digital models, and in particular Digital Twins (DTs), have seen a growing interest due to their ability to provide support in the development of more efficient systems and processes. This study presents the preliminary steps taken to develop a DT model for a marine Large Bore Dual-Fuel engine manufactured by Wärtsilä. The correlation between dependend and independent data set variables is presented in order to map the engine behaviour and validate the DT model before becoming operational. The analyses are conducted using the engine in gas mode, operating at 85% of Load (at the nominal speed of 600rpm). This operating point represents the typical target design for constant speed applications. The engine efficiency, emissions and combustion chamber parameters are investigated by varying the air-fuel mixture pressure, timing and duration parameters. Sensitivity analysis presents a tight relation between Nitrogen Oxides and Hydrocarbons (HC) emissions by varying the Scavenging Air Pressure. The HC emission function around the nominal value of the Pilot Fuel Injection Duration reverse its trend, while In Cylinder-Pressure and Combustion Duration functions presents opposite gradients. By advancing the Pilot Fuel Injection timing is shown an increase in Engine Efficiency respect to others input parameters.

Training-Dependent Gradients of Timescales of Neural Dynamics in the Primate Prefrontal Cortex and Their Contributions to Working Memory.

Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, for example, from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales are inherent properties of neurons and/or depend on training in a specific task and if the latter, how their modulations contribute to task performance. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition.

Sedimentary phosphorus burial in three contrasting boreal lakes in Finland

AbstractPermanent phosphorus (P) burial in sediment regulates lake trophic state over long timescales, but the controls on P burial are only partially understood. A diversity of biogeochemical settings may be found in lake sediments, which may have a strong impact on the processes controlling P burial from one location to another. Here, we investigate early diagenesis of P in three contrasting lakes in Southwest Finland. Eutrophic Lake Köyliönjärvi and mesotrophic Lake Pyhäjärvi have a history of nutrient loadings from agriculture, while Lake Vähäjärvi is an oligotrophic small forest lake, leading to potentially contrasting sediment biogeochemical dynamics. We combined porewater data and solid-phase sediment geochemical data to identify P phases in each system and investigate the dominant processes controlling P burial. Porewater profiles showed opposite gradients between the oligotrophic and the mesotrophic/eutrophic systems, implying net diffusive fluxes into and out of the sediments, respectively. Furthermore, sediment P data showed contrasting P speciation. Reactive P is buried in all systems, but the role of reducible iron (Fe) oxides in P retention is greater in mesotrophic/eutrophic lakes. In the oligotrophic system, aluminium (Al) oxides controlled P sorption into the sediment after diffusion from lake water. Evidence for vivianite formation was found only in the mesotrophic Lake Pyhäjärvi sediment, where 42–47% of total P was released in a Fe(II)-P specific extraction from the deeper part of the sediment column and vivianite crystals could be isolated from sediment samples.

Opposite latitudinal gradients for species richness and phylogenetic diversity of endemic snakes in the Atlantic Forest.

The decrease in species richness toward higher latitudes is an expected biogeographical pattern. This pattern could be related to particular environmental constraints and the evolutionary history of clades. However, species richness does not fully represent the evolutionary history of the clades behind their distributions. Phylogenetic diversity better clarifies the role of historical factors in biogeographical patterns. We analyzed environmental and historical drivers related to latitudinal variation in species richness and phylogenetic diversity of Atlantic Forest endemic snakes. We implemented species distribution models, from voucher-based locality points, to map the snake ranges and diversity. We used generalized additive mixed models to evaluate the relationships among the diversity metrics and area, topographical roughness, and past climate change velocity since the Last Maximum Glacial in the Atlantic Forest latitudinal gradient. Contrary to the expected general pattern, species richness was higher toward higher latitudes, being positively related to past climatic stability. Species richness also increased with total area and higher topographical roughness. Phylogenetic diversity, on the other hand, showed opposite relationships related to the same factors. Phylogenetic diversity increased with lower climatic stability in lower latitudes. Thus, dimensions of diversity were affected in different ways by historical and environmental constraints in this unique and threatened biodiversity hotspot.

Design and fabrication of multifunctional holographic optical elements in laser Doppler velocimeter.

Replacing the bulky traditional optical elements in the optical system with a holographic optical element (HOE) is conducive to the functional integration and volume miniaturization. However, when the HOE is used in the infrared system, the mismatch between the recording wavelength and the working wavelength will lead to the reduction of diffraction efficiency and the introduction of aberration, which will seriously affect the performance of the optical system. This paper proposes a design and fabrication method of multifunctional infrared HOEs that can be used in laser Doppler velocimeter (LDV), which can reduce the effect of wavelength mismatch on HOE performance while integrating the functions of the optical system. The restriction relationship and selection method of parameters in typical LDV are summarized; the decrease of diffraction efficiency due to the mismatch between recording and working wavelengths is compensated by designing the angle of signal and reference wave of the HOE; and the aberration caused by wavelength mismatch is compensated by cylindrical lens. The optical experiment shows that the HOE can produce two groups of fringes with opposite gradient, which proves the feasibility of the proposed method. Moreover, this method has a certain degree of universality, and it is expected to design and fabricate HOEs for any working wavelength in the near-infrared band.

Highly structured turbulence in high-mass star formation: An evolved infrared-dark cloud G35.20-0.74 N

Context. Massive stars are generally believed to form in environments characterized by supersonic turbulence. However, recent observations challenge this traditional view. High-spatial- and spectral-resolution observations of the Orion Molecular Cloud (OMC, the closest massive star formation region) and an infrared-dark cloud (IRDC) G35.39 (a typical distant massive star formation region) show a resolution-dependent turbulence, and that high-mass stars are forming exclusively in subsonic to transonic cores in those clouds. These studies demand a re-evaluation of the role of turbulence in massive star formation. Aims. We aim to study the turbulence in a typical massive-star-forming region G35.20-0.74 N (G35.20 in short) with sufficient spatial resolution to resolve the thermal Jeans length, and sufficient spectral resolution to resolve the thermal line width. Methods. We use the Atacama Large Millimeter/submillimeter Array (ALMA) dust continuum emission to resolve fragmentation, the Karl G. Jansky Very Large Array (JVLA) 1.2 cm continuum to trace ionized gas, and JVLA NH3 (1,1) to (7,7) inversion transition lines to trace line width, temperature, and dynamics. We fit those lines and remove line broadening due to channel width, thermal pressure, and velocity gradient to obtain a clean map of intrinsic turbulence. Results. We find that (1) the turbulence in G35.20 is overall supersonic, with mean and median Mach numbers 3.7 and 2.8, respectively. (2) Mach number decreases from 6–7 at a 0.1 pc scale to less than 3 toward the central cores at a 0.01 pc scale. (3) The central ALMA cores appear to be decoupled from the host filament, which is made evident by an opposite velocity gradient and significantly reduced turbulence. Because of intense star-formation activity in G35.20 (as compared to the relatively young and quiescent IRDC G35.39), the supersonic turbulence is likely replenished by protostellar outflows. G35.20 is therefore representative of an evolved form of IRDC G35.39. More observations of a sample of IRDCs are highly demanded in order to further investigate the role of turbulence in the initial conditions required for massive-star formation.

Simulations on Synchrotron Radiation Intensity and Rotation Measure of Relativistic Magnetized Jet PKS 1502+106

Strong γ-ray outbursts have been observed to emanate from PKS 1502+106, followed by highly variable fluxes in radio, visual, ultraviolet and X-ray bands. Numerical simulations have been conducted to relate the observations to potential theoretical models. The plasma attributes, such as mass density, plasma flow velocity and energy density, cannot be directly observed. However, the Stokes parameters of synchrotron radiation from the plasma can be measured to deduce the plasma attributes. Many studies have been conducted on synchrotron radiation intensity, with only a few on the rotation measure (RM) related to Faraday rotation. In this work, overpressured relativistic magnetized axisymmetric jets are simulated to acquire the synchrotron radiation maps, incorporating Faraday rotation, of the widely discussed jet, PKS 1502+106. The intensity maps and RM maps of the PKS 1502+106 are simulated under practical constraints, and compared with the available observation data to explore specific features of the jet. The simulated intensity maps match well with the observation data in size and shape. The observed spine–sheath polarization structure, sign change in the RM slice and opposite RM gradients have been reproduced. The conjecture of helical magnetic field morphology in the literature has also been validated by comparing the simulation results under different magnetic field morphologies.

Exploring variations and influencing factors of illegal adoption: A comparison between child trafficking and informal adoption

BackgroundIllegal adoption, which mainly includes child trafficking and informal adoption, has long been a prevalent social issue in China. However, the processes and patterns of illegal adoption are not well understood due to the scarcity of data. ObjectiveThe findings are expected to provide insightful clues for the government and the public to better understand the two categories of illegal adoption. Participants and settingThis study included 4296 trafficking cases and 4499 informal adoption cases between 1949 and 2018. The data came from the ‘Baby Coming Back Home’ (https://www.baobeihuijia.com) website, which is the most comprehensive commonweal forum established by nongovernmental volunteers for finding missing persons in China. MethodsMathematical statistics and hot spot analysis were used to visualize the spatiotemporal pattern of illegal adoption. ResultsChild trafficking and informal adoption show opposite gender preferences and different age gradients. The numbers of both cases peaked in the early 1990s and then dropped. More than 50 % of all trafficked children were male, whereas approximately 83 % cases of informal adoption were female between 1980 and 2000. Hot spots of illegal adoption have shifted from the cities of the Huai River Basin to the southeastern coastal cities over time, 39.40 % of trafficking cases occurred in rural residential areas, and 52.45 % of informal adoption cases were observed in hospitals. ConclusionsChild trafficking and informal adoption are two different ways of adopting children in China. The combination of the one-child policy and the traditional culture of son preference shaped the different characteristics of the illegal adoption of children during a critical period.

Enhancing Mean-Variance Mapping Optimization Using Opposite Gradient Method and Interior Point Method for Real Parameter Optimization Problems

The aim of optimization methods is to identify the best results in the search area. In this research, we focused on a mixture of the interior point method, opposite gradient method, and mean-variance mapping optimization, named IPOG-MVMO, where the solutions can be obtained from the gradient field of the cost function on the constraint manifold. The process was divided into three main phases. In the first phase, the interior point method was applied for local searching. Secondly, the opposite gradient method was used to generate a population of candidate solutions. The last phase involved updating the population according to the mean and variance of the solutions. In the experiments on real parameter optimization problems, three types of functions, which were unimodal, multimodal, and continuous composition functions, were considered and used to compare our proposed method with other meta-heuristics techniques. The results showed that our proposed algorithms outperformed other algorithms in terms of finding the optimal solution.

Synaptic gradients transform object location to action

To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3–5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly’s directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

Численное моделирование максимального перепада температур в термоэлектрической ветви из градиентно-варизонного сплава висмут-сурьма в области температур 70–120 К

Inhomogeneous bismuth-antimony alloys are the most efficient thermoelectrics at 100 K. This article describes a numerical simulation by means of COMSOL Multiphysics of the temperature field as a function of the current in a thermoelectric branch made of a gradient-inhomogeneous Bi100-x-Sbx al-loy within the semiconductor region of the interval 11 at. %< x<19 at. %. The model takes into account that the parameters of the substance affecting the thermoelectric figure of merit, namely ther-mal conductivity, thermoelectric power, and electrical conductivity, are variable along the branch. In this case, the alloy inhomogeneity and temperature gradients lie in the cleavage plane of the sample. To simulate this problem, the authors numerically solved a system of heat conduction equations and the generalized Ohm's law equations, taking into account continuously distributed heat sources, for which the Joule heat, the Thomson effect, and the Peltier effect are responsible. It can be seen from numerical calculations that in the region of 70–120 K, there is an increase in the maximum tempera-ture difference in the presence of opposite gradients of the antimony concentration and temperature in the sample, compared to unidirectional gradients or a homogeneous alloy. The results obtained were compared with experimental data for a thermal branch with the same inhomogeneity composi-tion (11 at. %<x<19 at. % Sb).

Efficient Carrier Confinement in AlGaN‐Based Deep‐Ultraviolet Light‐Emitting Diodes with a Composition‐Graded Electron‐Blocking Layer

The serious electron leakage and poor transport of hole injection layers in deep‐ultraviolet (DUV) light‐emitting diodes (LEDs) lead to an imbalance between the hole and electron currents, which reduces the device's performance. Herein, a new DUV LED structure is designed. The aluminum composition of the p‐type electron‐blocking layer (p‐EBL) gradually decreases from 0.95 to 0.75 along the growth direction, replacing the traditional bulk p‐EBL. When the injection current is 100 mA, the optical power of this structure is about 32% higher than that of the traditional structure. In addition, when the p‐EBL adopts the opposite gradient (the Al composition gradually increases from 0.75 to 0.95), the device performance suddenly drops dramatically. The related devices are simulated by Silvaco TCAD software. The results show that the performance outputs of the two opposite aluminum gradient growth modes are completely opposite. The proposed p‐EBL with a gradual step‐down Al composition along the growth direction helps to improve the efficiency of hole injection into multiple quantum wells (MQWs) and reduce the level of electron leakage. This work provides an effective solution for increasing the light output power of high‐performance DUV LEDs.

Progression of regional cortical cholinergic denervation in Parkinson's disease.

Cortical cholinergic deficits contribute to cognitive decline and other deficits in Parkinson's disease. Cross-sectional imaging studies suggest a stereotyped pattern of posterior-to-anterior cortical cholinergic denervation accompanying disease progression in Parkinson's disease. We used serial acetylcholinesterase PET ligand imaging to characterize the trajectory of regional cholinergic synapse deficits in Parkinson's disease, testing the hypothesis of posterior-to-anterior progression of cortical cholinergic deficits. The 16 Parkinson's disease subjects (4 females/12 males; mean age: 64.4 ± 6.7 years; disease duration: 5.5 ± 4.2 years; Hoehn & Yahr stage: 2.3 ± 0.6 at entry) completed serial 11C-methyl-4-piperidinyl propionate acetylcholinesterase PET scans over a 4-8 year period (median 5 years). Three-dimensional stereotactic cortical surface projections and volume-of-interest analyses were performed. Cholinergic synapse integrity was assessed by the magnitude, k 3, of acetylcholinesterase hydrolysis of 11C-methyl-4-piperidinyl propionate. Based on normative data, we generated Z-score maps for both the k 3 and the k 1 parameters, the latter as a proxy for regional cerebral blood flow. Compared with control subjects, baseline scans showed predominantly posterior cortical k 3 deficits in Parkinson's disease subjects. Interval change analyses showed evidence of posterior-to-anterior progression of cholinergic cortical deficits in the posterior cortices. In frontal cortices, an opposite gradient of anterior-to-posterior progression of cholinergic deficits was found. The topography of k 3 changes exhibited regionally specific disconnection from k 1 changes. Interval-change analysis based on k 3/k 1 ratio images (k 3 adjustment for regional cerebral blood flow changes) showed interval reductions (up to 20%) in ventral frontal, anterior cingulate and Brodmann area 6 cortices. In contrast, interval k 3 reductions in the posterior cortices, especially Brodmann areas 17-19, were largely proportional to k 1 changes. Our results partially support the hypothesis of progressive posterior-to-cortical cholinergic denervation in Parkinson's disease. This pattern appears characteristic of posterior cortices. In frontal cortices, an opposite pattern of anterior-to-posterior progression of cholinergic deficits was found. The progressive decline of posterior cortical acetylcholinesterase activity was largely proportional to declining regional cerebral blood flow, suggesting that posterior cortical cholinergic synapse deficits are part of a generalized loss of synapses. The disproportionate decline in regional frontal cortical acetylcholinesterase activity relative to regional cerebral blood flow suggests preferential loss or dysregulation of cholinergic synapses in these regions. Our observations suggest that cortical cholinergic synapse vulnerability in Parkinson's disease is mediated by both diffuse processes affecting cortical synapses and processes specific to subpopulations of cortical cholinergic afferents.