Frederick d'Oleire Uquillas

Princeton University | PU · Princeton Neuroscience Institute

The biological mechanisms that link β-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...

Tau and amyloid beta (Aβ) proteins accumulate along neuronal circuits in Alzheimer’s disease. Unraveling the genetic background for the regional vulnerability of these proteinopathies can help in understanding the mechanisms of pathology progression. To that end, we developed a novel graph theory approach and used it to investigate the intersection...

Loneliness is a perception of social and emotional isolation that increases in prevalence among older adults during the eighth decade of life. Loneliness has been associated with higher brain amyloid-β deposition, a biologic marker of Alzheimer’s disease, in cognitively normal older adults, suggesting a link with preclinical Alzheimer’s disease pat...

Judgments of learning (JOL) pertain to introspective metamemory processes evaluating how well information is learned. Using a functional magnetic resonance imaging (fMRI) task, we investigated the neural substrates of JOL predictions in a group of 105 cognitively unimpaired older adults from the Harvard Aging Brain Study. Associations of JOL perfor...

The organization of the basic tissue and functional properties of the cerebellum across development is unknown. Combining several large datasets, we demonstrate in the human cerebellum a static tissue gradient in adults that mirrors a similar growth-rate gradient across development. Quantitative tissue metrics corroborate unique densities of certai...

Reciprocity is often considered a precondition for sacrificial behaviors, with people being willing to make sacrifices in their relationships to better their collective interests and expecting their partners to do the same. However, whether relational sacrifices exist in a zero-sum game, wherein reciprocity cannot be established, remains unclear. T...

The genetic traits that underlie vulnerability to neuronal damage across specific brain circuits in Parkinson’s disease (PD) remain to be elucidated. In this study, we characterized the brain topological intersection between propagating connectivity networks in controls and PD participants and gene expression patterns across the human cortex – such...

The relationship between human brain connectomics and genetic evolutionary traits remains elusive due to the inherent challenges in combining complex associations within cerebral tissue. In this study, insights are provided about the relationship between connectomics, gene expression and divergent evolutionary pathways from non-human primates to hu...

Several autopsy studies recognize the locus coeruleus (LC) as the initial site of hyperphosphorylated TAU aggregation, and as the number of LC neurons harboring TAU increases, TAU pathology emerges throughout the cortex. By conjointly using dedicated MRI measures of LC integrity and TAU and amyloid PET imaging, we aimed to address the question whet...

Introduction: Cortical thinning is a marker of neurodegeneration in Alzheimer's disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD). Methods: Two hundred eleven participants (105 presenilin-1 [PSEN1] E280A mutation carriers, 16 wi...

Romantic love is a complex state that has been seen as similar to addiction. Previous task-based functional magnetic resonance imaging (fMRI) studies have shown that being in love is closely associated with functional brain changes in the reward and motivation system. However, romantic love-related functional connectivity network organization in re...

Background Autopsy studies report that the locus coeruleus (LC) is the first site to accumulate tau, after which it spreads topographically to the entorhinal cortex (EC) and limbic regions. Once tau has reached the cortex, its spread is assumed to occur via connectivity and to be facilitated by Aβ. We aimed to examine whether lower LC integrity is...

Background Tauopathy can be detected in the locus coeruleus (LC) decades before clinical symptoms or Aβ‐pathology. Following involvement of the LC, tau progresses to the medial temporal lobe (MTL), possibly via hyperactivity or connectivity. Given LC’s modulating role on brain function and its early involvement in proteinopathies that affect LC’s i...

Response inhibition is a critical cognitive ability underlying executive control over reactions to external cues, or inner requirements. Previous studies suggest that high arousal negative emotions (e.g., anger or fear) could impair response inhibition in implicit emotional stop signal tasks (eSSTs). However, studies exploring how low arousal negat...

Significance Previous research has explored the association between behavioral disorders and dysfunction in corresponding neural networks. For example, autism spectrum disorder, Prader–Willi syndrome, and Dravet syndrome are characterized by behavioral deficits in the visuomotor integration system. To date, few investigations have combined brain co...

Importance To reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults. Objective To determine whether wid...

Alzheimer's disease (AD) is associated with brain network dysfunction. Network-based investigations of brain connectivity have mainly focused on alterations in the strength of connectivity; however, the network breakdown in AD spectrum is a complex scenario in which multiple pathways of connectivity are affected. To integrate connectivity changes t...

The ability to accurately judge memory efficiency (meta-memory monitoring) for newly learned (episodic) information, is decreased in older adults and even worse in Alzheimer's disease (AD), whereas no differences have been found for semantic meta-memory. The pathological substrates of this phenomenon are poorly understood. Here, we examine the asso...

The neurobiological underpinnings of stuttering, a speech disorder characterized by disrupted speech fluency, remain unclear. While recent developments in the field have afforded researchers with the ability to pinpoint several genetic profiles associated with stuttering, how these specific genetic backgrounds impact neuronal circuits and how they...

Objective: Public health recommendations promote social engagement to reduce risk of cognitive decline and dementia. The objective of this study was to evaluate the longitudinal associations of social engagement and cognition in cognitively normal older adults with varying levels of neocortical amyloid-β, the Alzheimer's disease (AD) pathologic ma...

Romantic relationships are difficult to maintain novel and exciting for long periods of time, and individuals in love are known to engage in a variety of efforts to protect and maintain their romantic relationship. How to protect and maintain these relationships more effectively has, however, plagued people, psychologists, and therapists. Intimate...

Disproportionate anger and reactive aggression in response to provocation are core symptoms of intermittent-explosive disorder (IED). Previous research shows a link between the propensity for aggression in healthy individuals and altered functioning of prefrontal-limbic and default-mode networks (DMN) at rest when no provocation is present. In a pi...

Substance addiction (or drug addiction) is a neuropsychiatric disorder characterized by a recurring desire to continue taking the drug despite harmful consequences. Non-substance addiction (or behavioral addiction) covers pathological gambling, food addiction, internet addiction, and mobile phone addiction. Their definition is similar to drug addic...

The neural correlates underlying the influence of emotional interference on cognitive control remain a topic of discussion. Here, we assessed 16 neuroimaging studies that used an emotional Stroop task and that reported a significant interaction effect between emotion (stimulus type) and cognitive conflict. There were a total of 330 participants, eq...

Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG), and half were single and had never been in a romantic relatio...

Mobile phone dependence (MPD) is a behavioral addiction that has become an increasing public mental health issue. While previous research has explored some of the factors that may predict MPD, the underlying neural mechanisms of MPD have not been investigated yet. The current study aimed to explore the microstructural variations associated with MPD...

Deficits in prefrontal cortical (PFC) function have been consistently reported in individuals with cocaine use disorders (iCUD), and have separately been shown to improve with longer-term abstinence. However, it is less clear whether the PFC structural integrity possibly underlying these deficits is also modulated by sustained reduction in drug use...

Dysfunctional self-awareness has been posited as a key feature of drug addiction, contributing to compromised control over addictive behaviors. In the present investigation, we showed that, compared with healthy controls (n=13) and even individuals with remitted cocaine use disorder (n=14), individuals with active cocaine use disorder (n=8) exhibit...

Romantic love is a motivational state associated with a desire to enter or maintain a close relationship with a specific other person. Studies with functional magnetic resonance imaging (fMRI) have found activation increases in brain regions involved in processing of reward, emotion, motivation when romantic lovers view photographs of their partner...

Individuals prone to reactive aggression can experience difficulty inhibiting aggressive responses in emotionally salient situations, yet little is known about their brain functioning when not challenged. We acquired resting-state brain activity using functional MRI in reactive aggressive individuals (RA, n=12) and controls (n=12), who also complet...