Deep learning combining FDG-PET and neurocognitive data accurately predicts MCI conversion to Alzheimer's dementia 3-year post MCI diagnosis.

INTRODUCTION: This study reports a novel deep learning approach to predict mild cognitive impairment (MCI) conversion to Alzheimer's dementia (AD) within three years using whole-brain fluorodeoxyglucose (FDG) positron emission tomography (PET) and cognitive scores (CS). METHODS: This analysis consisted of 150 normal controls (CN), 257 MCI, and 205  AD subjects from ADNI. FDG-PET and CS were obtained at MCI diagnosis to predict AD conversion within three years of MCI diagnosis using convolutional neural networks. RESULTS: Neurocognitive scores predicted better than FDG-PET per se, but the best model was a combination of FDG-PET, age, and neurocognitive data, yielding an AUC of 0.785 ± 0.096 and a balanced accuracy of 0.733 ± 0.098. Saliency maps highlighted putamen, thalamus, inferior frontal gyrus, parietal operculum, precuneus cortices, calcarine cortices, temporal gyrus, and planum temporale to be important for prediction. DISCUSSION: Deep learning accurately predicts MCI conversion to AD and provides neural correlates of brain regions associated with AD conversion.

Remote Associations Between Tau and Cortical Amyloid-ß Are Stage-Dependent.

Background: Histopathologic studies of Alzheimer's disease (AD) suggest that extracellular amyloid-ß (Aß) plaques promote the spread of neurofibrillary tau tangles. However, these two proteinopathies initiate in spatially distinct brain regions, so how they interact during AD progression is unclear. Objective: In this study, we utilized Aß and tau positron emission tomography (PET) scans from 572 older subjects (476 healthy controls (HC), 14 with mild cognitive impairment (MCI), 82 with mild AD), at varying stages of the disease, to investigate to what degree tau is associated with cortical Aß deposition. Methods: Using multiple linear regression models and a pseudo-longitudinal ordering technique, we investigated remote tau-Aß associations in four pathologic phases of AD progression based on tau spread: 1) no-tau, 2) pre-acceleration, 3) acceleration, and 4) post-acceleration. Results: No significant tau-Aß association was detected in the no-tau phase. In the pre-acceleration phase, the earliest stage of tau deposition, associations emerged between regional tau in medial temporal lobe (MTL) (i.e., entorhinal cortex, parahippocampal gyrus) and cortical Aß in lateral temporal lobe regions. The strongest tau-Aß associations were found in the acceleration phase, in which tau in MTL regions was strongly associated with cortical Aß (i.e., temporal and frontal lobes regions). Strikingly, in the post-acceleration phase, including 96% of symptomatic subjects, tau-Aß associations were no longer significant. Conclusions: The results indicate that associations between tau and Aß are stage-dependent, which could have important implications for understanding the interplay between these two proteinopathies during the progressive stages of AD.

Distinct and joint effects of low and high levels of Aß and tau deposition on cortical thickness.

Alzheimer's disease (AD) is defined by the presence of Amyloid-ß (Aß),tau, and neurodegeneration (ATN framework) in the human cerebral cortex. Yet, prior studies have suggested that Aß deposition can be associated with both cortical thinning and thickening. These contradictory results are attributed to small sample sizes, the presence versus absence of tau, and limited detectability in the earliest phase of protein deposition, which may begin in young adulthood and cannot be captured in studies enrolling only older subjects. In this study, we aimed to find the distinct and joint effects of Aß andtau on neurodegeneration during the progression from normal to abnormal stages of pathologies that remain elusive. We used18F-MK6240 and 18F-Florbetaben/18F-Florbetapir positron emission tomography (PET) and magnetic resonance imaging (MRI) to quantify tau, Aß, and cortical thickness in 590 participants ranging in age from 20 to 90. We performed multiple regression analyses to assess the distinct and joint effects of Aß and tau on cortical thickness using 590 healthy control (HC) and mild cognitive impairment (MCI) participants (141 young, 394 HC elderlies, 52 MCI). We showed thatin participants with normal levels of global Aßdeposition, Aß uptakewassignificantly associated with increasedcortical thickness regardless of tau (e.g., left entorhinal cortex with t > 3.241, p < 0.0013). The relationship between tau deposition and neurodegeneration was more complex: in participants with abnormal levels of global tau, tau uptake was associated with cortical thinning in several regions of the brain (e.g., left entorhinal with t < -2.80, p < 0.0096 and left insula with t-value < -4.284, p < 0.0001), as reported on prior neuroimaging and neuropathological studies. Surprisingly, in participants with normal levels of global tau, tau was found to be associated with cortical thickening. Moreover, in participants with abnormal levels of global Aßandtau, theresonancebetween them, defined as their correlation throughout the cortex, wasassociated strongly with cortical thinning even when controlling for a direct linear effect. We confirm prior findings of an association between Aß deposition and cortical thickening and suggest this may also be the case in the earliest stages of deposition in normal aging. We also illustrate that resonance between high levels of Aß and tau uptake is strongly associated with cortical thinning, emphasizing the effects of Aß/tau synergy inAD pathogenesis.

Mid-Frontal Theta Modulates Response Inhibition and Decision Making Processes in Emotional Contexts.

Inhibitory control is an integral part of executive functions. In this study, we report event-related spectral perturbation (ERSP) results from 15 healthy adults performing an emotional stop-signal task with the use of happy, disgusted, and neutral emotional faces. Our ERSP results at the group level suggest that changes in low frequency oscillatory power for emotional and neutral conditions start at as early as 200 ms after stimulus onset and 300 ms before button press for successful go trials. To quantify the dynamics of trial-by-trial theta power, we applied the hierarchical drift diffusion model to single-trial ERSP at the mid-frontal electrode site for the go condition. Hierarchical drift diffusion modeling (HDDM) assigned higher frontal low-frequency oscillatory power for evidence accumulation in emotional contexts as compared to a neutral setting. Our results provide new evidence for dynamic modulation of sensory processing of go stimuli in inhibition and extend our knowledge for processing of response inhibition in emotional contexts.

Resting heart rate variability in young women is a predictor of EEG reactions to linguistic ambiguity in sentences.

Recent research has found a relationship between heart rate variability (HRV) and cognitive control mechanisms underlying various experimental tasks. This study explored the interaction between gender and resting-state HRV in brain oscillatory activity during visual recognition of linguistic ambiguity while taking state and trait anxiety scores into account. It is well known that stress or anxiety increases arousal levels, particularly under uncertainty situations. We tasked 50 young Mandarin speakers (26 women; average age 26.00 ±â€¯4.449) with the recognition of linguistic ambiguity in English (foreign) sentences with the purpose of imposing a sense of uncertainty in decision-making. Our results revealed a dependency between resting-state HRV and theta/alpha power in individual women. Low HRV women showed stronger theta/alpha desynchronization compared with their high HRV counterparts, independent of topographic localization. However, low and high HRV men exhibited comparable theta/alpha activity. Trait anxiety scores affected alpha power in the parieto-occipital regions, whereas men with higher scores and women with lower scores showed stronger alpha desynchronization. We posit that stress-provoking situations may impose additional effects on theta/alpha desynchronization in the frontal and temporal regions, a condition in which the interdependency between brain oscillatory activity and resting-state HRV could interact with cognitive control differently in men and women.