Anderson Winkler

University of Texas Rio Grande Valley · Department of Human Genetics

Objectives We assessed cortical changes in children with drug-resistant focal epilepsy using surface-based T1 and T2 relaxometry (qT1 and qT2), to probe alterations in tissue-microstructure, and their relationship to clinical parameters. Methods Data Acquisition89 children were scanned unsedated on a 3T Achieva-TX scanner (Philips Healthcare) – 43...

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. As well, recent work has shown that individual differences in error monitoring moderate temperamental risk for anxiety and that this moderation changes with age. We investigated age dif...

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal cou...

Introduction: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, res...

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Here we investigated cortical asymmetries in 442 healthy term-born neonates using structural and functional magnetic resonance images from the Developing Human Connectome Project. Our results demonstrate that...

Background: The highest risk of depression is conveyed by insomnia. This risk can be mitigated by sleep interventions. Understanding brain mechanisms underlying increased emotional stability following insomnia treatment could provide insight relevant to the prevention of depression. We here investigate how different sleep interventions alter emoti...

Although we understand how serotonin receptors function at the single-cell level, what role different serotonin receptors play in regulating brain-wide activity and, in turn, human behavior, remains unknown. Here, we developed transcriptomic–neuroimaging mapping to characterize brain-wide functional signatures associated with specific serotonin rec...

Purpose of the Review This review describes approaches to research on anxiety that attempt to link neural correlates to treatment response and novel therapies. The review emphasizes pediatric anxiety disorders since most anxiety disorders begin before adulthood. Recent Findings Recent literature illustrates how current treatments for anxiety manif...

Our current understanding of focal epilepsy is evolving as increasing evidence suggests that tissue abnormalities may extend beyond the focus. In adults, widespread structural changes remote from the putative epileptic focus have been demonstrated with MRI, predominantly using morphological markers. However, the underlying pathophysiology of these...

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level infere...

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. We investigated age differences in neural responses linked to performance monitoring using a multimodal approach. The approach combined functional MRI and source localization of event-r...

Background and objective Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that le...

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar a...

There is strong evidence for brain-related abnormalities in COVID-191-13. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twice...

Background and Objective Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that le...

Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. W...

Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research i...

COVER ILLUSTRATION This cover illustration is the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Consortium's logo, depicting a human brain surrounded by genetic information. The logo reflects the focus of the consortium which is to study the human brain from around the world through neuroimaging and genetics. This marks the ten-yea...

Chronic pain is characterised by an ongoing and fluctuating intensity over time. Here, we investigated how the trajectory of the patients' endogenous pain is encoded in the brain. In repeated functional MRI (fMRI) sessions, 20 patients with chronic back pain and 20 patients with chronic migraine were asked to continuously rate the intensity of thei...

Although we understand how serotonin receptors function at the single-cell level, what role different serotonin receptors play in regulating brain-wide activity and, in turn, human behaviour, remains unknown. Here, we developed transcriptomic-neuroimaging mapping to characterise brain-wide functional signatures associated with specific serotonin re...

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Using a new left-right symmetric, spatiotemporal cortical surface atlas, we investigated cortical asymmetries in 442 healthy newborn infants soon after birth, using structural and functional magnetic resonanc...

This Special Issue of Human Brain Mapping is dedicated to a 10-year anniversary of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium. It reports updates from a broad range of international neuroimaging projects that pool data from around the world to answer fundamental questions in neuroscience. Since ENIGMA was formed i...

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through th...

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we car...

Purpose of review: Anxiety disorders are some of the most common psychiatric diagnoses in children and adolescents, but attempts to improve outcome prediction and treatment have stalled. This review highlights recent findings on neural indices related to fear and anxiety that provide novel directions for attempts to create such improvements. Rece...

There is strong evidence for brain-related abnormalities in COVID-19 1-13 . It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51-81) imaged twi...

Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain les...

The hippocampus and the entorhinal cortex are considered the main brain structures for allocentric representation of the external environment. Here, we show that the amygdala and the ventral visual stream are involved in allocentric representation. Thirty-one young men explored 35 virtual environments during high-resolution functional magnetic reso...

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity,...

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we car...

Abstract This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci as...

Objective Infant amygdala connectivity correlates with maternal reports of infant temperament characterized by novelty-evoked distress and avoidance. However, no studies examine how human infant amygdala connectivity relates to direct observations of novelty-evoked distress in human infants. The current study examines the link between amygdala conn...

Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improv...

Background Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis (CCA) designed to model mutual dependencies between symptom dimensions and neural measures. We map the multivariate associations that intr...

We investigated how the trajectory of pain patients’ ongoing and fluctuating pain is encoded in the brain. In repeated fMRI sessions, 20 chronic back pain patients and 20 chronic migraineurs were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain...

The World Health Organization (WHO) promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and brain development are not fully understood. Here, we asked whether a brain – physical latent mode of covariation underpins the relationship between physical activity, fit...

We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at 7 tesla. Partici...

We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at seven tesla. Par...

We investigated how the attenuation of pain with cognitive interventions affects brain connectivity using neuroimaging and a whole brain novel analysis approach. While receiving tonic cold pain, 20 healthy participants performed three different pain attenuation strategies during simultaneous collection of functional imaging data at seven tesla. Par...

While there is strong evidence from observational studies that physical activity is associated with reduced risk of cognitive decline and dementia, the extent to which aerobic training interventions impact on cognitive health and brain structure remains subject to debate. In a pilot study of 46 healthy older adults (66.6 years ± 5.2 years, 63% fema...

Magnetic Resonance Spectroscopy (MRS) allows for the non-invasive quantification of neurochemicals and has the potential to differentiate between the pathologically distinct diseases, multiple sclerosis (MS) and AQP4Ab-positive neuromyelitis optica spectrum disorder (AQP4Ab-NMOSD). In this study we characterised the metabolite profiles of brain les...

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging meth...

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA‐Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega‐analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...

Canonical correlation analysis (CCA) has become a key tool for population neuroimaging, allowing investigation of associations between many imaging and non-imaging measurements. As age, sex and other variables are often a source of variability not of direct interest, previous work has used CCA on residuals from a model that removes these effects, t...

The relative contributions of metric and chronological time in the encoding of episodic memories are unknown. One hundred one healthy young adults viewed 48 unique episodes of visual events and were later tested on recall of the order of events (chronological time) and the precise timing of events (metric time). The behavioral results show that met...

The current study examined the link between temperamental reactivity in infancy and amygdala development in middle childhood. A sample (n = 291) of four-month-old infants was assessed for infant temperament, and two groups were identified: those exhibiting negative reactivity (n = 116) and those exhibiting positive reactivity (n = 106). At 10 and 1...

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodolo...

The multiple testing problem arises not only when there are many voxels or vertices in an image representation of the brain, but also when multiple contrasts of parameter estimates (that represent hypotheses) are tested in the same general linear model. We argue that a correction for this multiplicity must be performed to avoid excess of false posi...

Canonical correlation analysis (CCA) has become a key tool for population neuroimaging for allowing investigation of association between many imaging and non-imaging variables. As age, sex and other variables are often a source of variability not of direct interest, previous work has used CCA on residuals from a model that removes these effects, th...

Previous studies suggest that gyrification is associated with superior cognitive abilities in humans, but the strength of this relationship remains unclear. Here, in two samples of related individuals (total N = 2882), we calculated an index of local gyrification (LGI) at thousands of cortical surface points using structural brain images and an ind...

White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity meas...

Objective: To determine whether brain imaging markers of tissue microstructure can detect the effect of disease progression across the preclinical stages of Huntington's disease. Methods: Longitudinal microstructural changes in diffusion imaging metrics (mean diffusivity and fractional anisotropy) were investigated in participants with presympto...

Background: While translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patien...

The perception of pain activates a number of brain regions and processes that are involved in its sensory, emotional, cognitive, and affective aspects; all of which require a flexible functional connectivity between local and distant brain regions. Here, we investigate how the attenuation of pain with cognitive interventions affects the strength of...

Neuroimaging studies typically focus on either resting state or task-based fMRI data. Prior research has shown that similarity in functional connectivity between rest and cognitive tasks, interpreted as reconfiguration efficiency, is related to task performance and IQ. Here, we extend this approach from adults to children, and from cognitive tasks...