Tamara Hershey

Washington University in St. Louis | WUSTL , Wash U · Department of Psychiatry

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear a...

Childhood obesity has been associated with lower cognitive performance and worse mental health in cross-sectional studies. However, it is unclear whether these findings extend longitudinally and in what causal direction. Using data from the Adolescent Brain Cognitive Development (ABCD) Study (maximum analytical n = 6671, 48.3% girls, 42.8% non-Whit...

COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our stu...

Objective: In preclinical models, insulin resistance in the dorsal striatum (DS) contributes to overeating. Although human studies support the concept of central insulin resistance, they have not investigated its effect on consummatory reward-induced brain activity. Methods: Taste-induced activation was assessed in the caudate and putamen of the...

COVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our stu...

Objective: Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity...

Obesity, depression and Alzheimer's disease (AD) are three major interrelated modern health conditions with complex relationships. Early-life depression may serve as a risk factor for AD, while late-life depression may be a prodrome of AD. Depression affects approximately 23% of obese individuals, and depression itself raises the risk of obesity by...

Importance: Lower neighborhood and household socioeconomic status (SES) are associated with negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter and via what mechanisms. Objective: To assess whether and how neighborhood and household SES are independently associated with chi...

Neuroinflammation is both a consequence and driver of overfeeding and weight gain in rodent obesity models. Advances in magnetic resonance imaging (MRI) enable investigations of brain microstructure that suggests neuroinflammation in human obesity. To assess the convergent validity across MRI techniques and extend previous findings, we used diffusi...

Background: Converging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral and neuro-inflammation in depression is unclear. Here using data from the UK Biobank, we estimated associations among depression, C-reactive protein as a measure of peripheral inflammation (CRP), and neuroinflammation...

Neuroinflammation is both a consequence and driver of overfeeding and weight gain in rodent obesity models. Advances in magnetic resonance imaging (MRI) enable investigations of brain microstructure that suggests neuroinflammation in human obesity. To assess the convergent validity across MRI techniques and extend previous findings, we used diffusi...

Wolfram syndrome is a rare disease characterized by diabetes, neurodegeneration, loss of vision, and audition. We recently found, in a young sample of participants (mean age 15 yrs), that Wolfram syndrome was associated with impairment in smell identification with normal smell sensitivity and whole-mouth taste function. However, these senses were a...

Objective Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity...

Importance Both neighborhood and household socioeconomic disadvantage relate to negative health outcomes and altered brain structure in children. It is unclear whether such findings extend to white matter development, and via what mechanisms socioeconomic status (SES) influences the brain. Objective To test independent associations between neighbor...

We present a single-subject level functional mapping of cortical activity using high-density diffuse optical tomography with the goal to improve reproducibility of maps at an individual level while also revealing subject-specific features that are often ignored by group-level generalizations.

Converging evidence suggests that elevated inflammation may contribute to depression. Yet, the link between peripheral and neuro~inflammation in depression is unclear. Here using data from the UK Biobank (n=11,512), we estimated associations among depression, C~reactive protein as a measure of peripheral inflammation (CRP), and neuroinflammation as...

Importance Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Set...

Background Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the WFS1 gene, which leads to an exaggerated endoplasmic reticulum (ER) stress response. The disorder is typically characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy, hearing loss, and neurodegenerative features. Existing l...

Purpose : To report long-term ophthalmic findings in Wolfram syndrome, including rates of visual decline, macular thinning, retinal nerve fiber layer (RNFL) thinning and outer plexiform lamination (OPL). Design : Single-center, cohort study Methods : Thirty-eight participants were recruited and underwent a complete ophthalmic examination as well...

Wolfram syndrome is a rare disease caused by pathogenic variants in the WFS1 gene with progressive neurodegeneration. As an easily accessible biomarker of progression of neurodegeneration has not yet been found, accurate tracking of the neurodegenerative process over time requires assessment by costly and time-consuming clinical measures and brain...

Objective To characterize the association between environmental (residential air) manganese (Mn) exposure and cognitive performance, focusing on cognitive control, in a Black African population. Methods We administered the Go-No-Go, Letter Number Sequence, and Matrix Reasoning tests to population-based samples age ≥40 from a high Mn (smelter) expo...

Objective 1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. 2) Determine whether C-peptide could be used as a marker of diabetes progression in interve...

Background and purpose: The hippocampus is a frequent focus of quantitative neuroimaging research, and structural hippocampal alterations are related to multiple neurocognitive disorders. An increasing number of neuroimaging studies are focusing on hippocampal subfield regional involvement in these disorders using various automated segmentation ap...

Objective Basal ganglia regions are part of the brain’s reward-processing networks and are implicated in the neurobiology of obesity and eating disorders. This study examines basal ganglia microstructural properties in adults with and without obesity. Methods Diffusion basis spectrum imaging (DBSI) images were analyzed to obtain putative imaging m...

BACKGROUND Wolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene...

Type 1 diabetes (T1D) is one of the most common chronic childhood diseases, and its prevalence is rapidly increasing. The management of glucose in T1D is challenging, as youth must consider a myriad of factors when making diabetes care decisions. This task often leads to significant hyperglycemia, hypoglycemia, and glucose variability throughout th...

Objective To characterize the association between residential environmental manganese (Mn) exposure and depression and anxiety, given prior associations among occupationally-exposed workers. Methods We administered the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) to 697 study participants in their preferred language...

Objective: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia. Research design and methods: One hundred forty-four children with type 1...

Background: Obesity is related to quantitative neuroimaging abnormalities including reduced gray matter volumes and impaired white matter microstructural integrity, although the underlying mechanisms are not well understood. Objective: We assessed influence of obesity on neuroinflammation imaging that may mediate brain morphometric changes. Esta...

UNSTRUCTURED Type 1 diabetes (T1D) is one of the most common chronic childhood diseases, and its prevalence is rapidly increasing. The management of glucose in T1D is challenging, as youth must consider a myriad of factors when making diabetes care decisions. This task often leads to significant hyperglycemia, hypoglycemia, and glucose variability...

Abstract Background Wolfram syndrome is a rare genetic disease characterized by insulin-dependent diabetes, optic nerve atrophy, sensorineural hearing loss and neurodegeneration. Although olfactory dysfunction, a classical clinical marker of neurodegenerative processes, has been reported in Wolfram syndrome, its use as a clinical marker in Wolfram...

Background Deep brain stimulation of the subthalamic nucleus is a widely used adjunctive therapy for motor symptoms of Parkinson's disease, but with variable motor response. Predicting motor response remains difficult, and novel approaches may improve surgical outcomes as well as the understanding of pathophysiological mechanisms. The objective of...

BACKGROUND AND PURPOSE: Wolfram syndrome is a rare genetic disease with characteristic brain involvement. We reviewed the brain MR images of patients with Wolfram syndrome to determine the frequency and characteristics of common neuroradiologic findings. MATERIALS AND METHODS: We retrospectively reviewed the imaging data of patients with genetical...

Background Wolfram syndrome is a rare endoplasmic reticulum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, preclinical studies in cell and rodent models suggest that therape...

Motion‐induced artifacts can significantly corrupt optical neuroimaging, as in most neuroimaging modalities. For high‐density diffuse optical tomography (HD‐DOT) with hundreds to thousands of source‐detector pair measurements, motion detection methods are underdeveloped relative to both functional magnetic resonance imaging (fMRI) and standard func...

Background/Aims Age-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomiz...

Wolfram Syndrome (WFS) is a rare, genetic, neurodegenerative disorder with associated features of diabetes mellitus (DM), diabetes insipidus, deafness, and optic atrophy. In order to design intervention studies, concrete markers of disease progression are required. DM in WFS is believed to be due to endoplasmic reticulum stress-induced failure of i...

Background: Reward behaviors including those related to eating are influenced by output from the ventral striatum (VS), dorsal striatal [caudate(Cau) and putamen(Put)]and hypothalamus (HTH). We hypothesized that weight loss would induce modifications in activation in these regions of interest (ROI) during a consummatory reward task. Methods: We rec...

Motion-induced artifacts can significantly corrupt optical neuroimaging, as in most neuroimaging modalities. For high-density diffuse optical tomography (HD-DOT) with hundreds to thousands of source-detector pair measurements, motion detection methods are underdeveloped relative to both functional magnetic resonance imaging (fMRI) and standard func...

Objective: This study determined whether striatal dopamine (DA) release is affected by food ingestion and whether the DA response to high-calorie food images is greater in the fasted than in the fed state in people with obesity. Methods: Striatal DA release was evaluated in 10 people with obesity and prediabetes after consuming a meal to satiati...

Remote limb ischemic conditioning (RLIC) is a clinically feasible method in which brief, sub-lethal bouts of ischemia protects remote organs or tissues from subsequent ischemic injury. A single session of RLIC can improve exercise performance and increase muscle activation. The purpose of this study, therefore, was to assess the effects of a brief,...

BACKGROUND : Wolfram syndrome is a rare genetic disease characterized by insulin-dependent diabetes, optic nerve atrophy, sensorineural hearing loss and neurodegeneration. Although olfactory dysfunction, a classical clinical marker of neurodegenerative processes, has been reported in Wolfram syndrome, its use as a clinical marker in Wolfram is limi...

Human obesity is associated with low-grade chronic systemic inflammation, alterations in brain structure and function, and cognitive impairment. Rodent models of obesity show that high-calorie diets cause brain inflammation (neuroinflammation) in multiple regions, including the hippocampus, and impairments in hippocampal-dependent memory tasks. To...

BACKGROUND: Wolfram syndrome is a rare genetic disease characterized by insulin-dependent diabetes, optic nerve atrophy, sensorineural hearing loss and neurodegeneration. Although olfactory dysfunction, a classical clinical marker of neurodegenerative processes, has been reported in Wolfram syndrome, its use as a clinical marker in Wolfram is limit...

Background: Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep qual...

Wolfram syndrome is a rare multisystem disorder caused by mutations in WFS1 or CISD2 genes leading to brain structural abnormalities and neurological symptoms. These abnormalities appear in early stages of the disease. The pathogenesis of Wolfram syndrome involves abnormalities in the endoplasmic reticulum (ER) and mitochondrial dynamics, which are...

Remote limb ischemic conditioning (RLIC) is a clinically feasible method of promoting tissue protection against subsequent ischemic insult. Recent findings from our lab demonstrated that RLIC robustly enhances motor learning in young, healthy humans. The next step is to determine which individuals would receive maximum benefit from RLIC before appl...

Remote limb ischemic conditioning (RLIC) is a technique in which tissues distant from the target organ are exposed to brief, sub-lethal bouts of ischemia. The effects of remotely applied ischemic conditioning are systemically transferred to the target organ, and typically manifested as protection from subsequent ischemic injury. Previous studies in...

Background: The extent to which glycemic exposure adversely impacts the developing brain in young children with early-onset type 1 diabetes (T1D) is controversial. Methods: As part of the multisite DirecNet Study, we performed structural MRI at three time points (baseline, 18 months and approximately 2.9 years after the second visit) in 137 childre...

Background: Subtle but significant cognitive differences between youth with and without type 1 diabetes (T1D) have been observed and found to be related to chronic hyperglycemia. We report continued follow-up of prospectively acquired cognitive data obtained over 4.5 years in a large cohort of young children with and without T1D. Methods: 181 child...

Background: The effect of dysglycemia on brain development and cognition is not well understood. Methods: In a multi-site study, we examined brain activation in 93 children with T1D (mean age 11.5 ± 1.8 years) and 57 nondiabetic children (mean age 11.8 ± 1.5 years) as they performed a classic executive function paradigm, the Go/No-Go task. Particip...

Wolfram syndrome is a rare, progressive neurodegenerative disorder characterized by juvenile-onset diabetes, optic nerve atrophy and mutation of the WFS1 gene. Calcium dyshomeostasis is a key mechanism underlying neuronal and pancreatic β-cell death and dysfunction in this endoplasmic reticulum (ER) disorder. Dantrolene sodium is an FDA-approved mu...

This chapter focuses on the neurocognitive effects of diabetes mellitus, particularly type 1 and type 2 diabetes. Although many of the side effects of diabetes—such as retinopathy, nephropathy, and peripheral neuropathy—are well known, the consequences on cognition have received comparatively little attention. These consequences will become more im...

Introduction Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep qual...

Wolfram syndrome is a rare disease caused by mutations in the WFS1 gene leading to symptoms in early to mid-childhood. Brain structural abnormalities are present even in young children, but it is not known when these abnormalities arise. Such information is critical in determining optimal outcome measures for clinical trials and in understanding th...

Endoplasmic reticulum (ER) stress in beta cells is an important pathogenic component of both type 1 and type 2 diabetes mellitus, as well as genetic forms of diabetes, especially Wolfram syndrome. However, there are currently no convenient ways to assess ER stress in beta cells, raising the need for circulating ER stress markers indicative of beta...

Objective: This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes. Research design and methods: Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participate...

Background Wolfram syndrome (WFS) is a rare autosomal recessive disease with clinical manifestations of diabetes mellitus (DM), diabetes insipidus (DI), optic nerve atrophy (OA) and sensorineural hearing loss (SNHL). Although SNHL is a key symptom of WFS, there is limited information on its natural history using standardized measures. Such informat...

Title: Effects of Remote Limb Ischemic Conditioning on Motor Learning and Muscle Strength in Healthy Young Adults: Phase I Randomized Controlled Trial Background: Remote ischemic conditioning (IC) is the phenomenon in which brief organ ischemia induces endogenous response such that a different (remote) organ is protected against subsequent ischem...

The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the hyp...

Aims/hypothesisPrior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the devel...

Background: The inclusion of milk in school feeding is accepted as good nutritional practice, but specific benefits remain uncertain. Objective: The objective was to determine whether consumption of 8.8 g milk protein/d given as milk powder with a multiple micronutrient-enriched porridge resulted in greater increases in linear growth and Cambrid...

Introduction: Wolfram syndrome (WFS) is a neurodegenerative disorder characterized by childhood-onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing impairment and commonly bladder and bowel dysfunction. We hypothesize that there is an association between smaller pons, which contains the pontine micturition center, and abnorma...

Introduction: Wolfram Syndrome (WFS) is a rare genetic disease associated with a variety of progressive metabolic and neurologic impairments. Previous research has focused on WFS-related impairments and biomarkers for disease progression; however, information about how WFS impacts participation in daily activities is lacking. Methods: WFS (n=45;...

Background/aims To report alterations in visual acuity and visual pathway structure over an interval of 1–3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination. Methods A...

Older adults are the largest consumer of cable news, which includes negative and politicized content and may constitute a daily stressor. As older adults are also vulnerable to the negative consequences of stress, we hypothesized that cable news-watching could induce a stress reaction and impair cognitive function. We tested exposures to cable news...

The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) determines the variability of motor and non-motor responses across Parkinson disease (PD) patients. We previously tested that hypothesis us...

Objective: To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints. To explore decreased hypothalamic-pituitary-adrenal (HPA) axis activity as a possible mechanism. Methods: 103 adults aged 65 years or older with an anxiety...

Supp. Table S1 Patients included in the genotype‐phenotype analysis.

Objective: To investigate daily function among individuals with Wolfram Syndrome (WFS) and examine whether any limitations are related to disease-related symptoms. Methods: WFS (n = 31), Type 1 diabetic (T1DM; n = 25), and healthy control (HC; n = 29) participants completed the Pediatric Quality of Life Questionnaire (PEDSQL) Self and Parent Rep...

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1,...

Background: Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. Methods: W...

IN BRIEF In children and adolescents with type 1 diabetes, exposure to glycemic extremes (severe hypoglycemia, chronic hyperglycemia, and diabetic ketoacidosis) overlaps with the time period of most active brain and cognitive development, leading to concerns that these children are at risk for cognitive side effects. This article summarizes the exi...

The authors tested whether 2 doses of remote limb ischemic conditioning (RLIC), induced via blood pressure cuff inflation, enhanced motor and cognitive learning to an equal extent, and explored a panel of blood biomarkers of RLIC. Thirty-two young adults were randomized to 3 groups and underwent a 7-day protocol of RLIC/sham followed by motor and c...

Sustained dysregulation of blood glucose (hyper- or hypoglycemia) associated with type 1 diabetes (T1D) has been linked to cognitive deficits and altered brain anatomy and connectivity. However, a significant gap remains with respect to how T1D affects spontaneous at-rest connectivity in young developing brains. Here, using a large multisite study,...

Objective: Cross-sectional studies find altered cognition in youth with type 1 diabetes mellitus (T1DM). However, few longitudinal studies have examined the trajectories of their cognitive performance over time. The aims of this study were to explore longitudinal change in cognitive function in youth with T1DM as compared with nondiabetic sibling...

Objective: Differences in cognition and brain structure have been found in youth with type 1 diabetes compared with controls, even after relatively short disease duration. To determine whether severity of clinical presentation contributes to these differences, we obtained structural magnetic resonance imaging (MRI) scans in youth ages 7-17 who wer...

Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships between these variables and the impac...

In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are non-selec...

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However,...

Background and Purpose: Remote limb ischemic conditioning (RLIC), delivered through brief intermittent bouts of blood pressure cuff inflation on the arm, has recently been shown to have neuroprotective effects. Because the mechanisms through which RLIC promotes tissue protection are multifactorial and epigenetic, RLIC holds promise as a neurorecove...

Objectives: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. Methods: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean a...

Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural magnetic resonance imaging was performed on 141 children with diabetes (ages 4-10 years at study entry) and 69 age-matched controls at two time points spaced 18 months apart. For the children with diabetes, HbA1c was 7.9±0.9% (...