- 857 364-2946
William Milberg
Harvard University, Psychiatry, Faculty Member
Research Interests: Cardiology, Dementia, Obesity, Cognition, Medicine, and 15 moreBrain, Humans, Internal Medicine, Hypertension, Diabetes mellitus, Disease, Hypercholesterolemia, Risk factors, Risk Factor, Cognitive impairment, Diabetes complications, Cardiovascular Diseases, Risk Factors, cardiovascular disease risk factor, and Cardiovascular medicine and haematology
Objectives: Post-traumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely... more
Objectives: Post-traumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely characterized. Methods: In the current study, we examined 187 post-9/11 Veterans (Mean age = 32.8 years, 87% male) diagnosed with PTSD who performed two extensive clinical and cognitive evaluations approximately two years apart. Results: We found that greater PTSD symptom reductions over time were related to lower lifetime drinking history and better baseline inhibitory control ability (Color-Word Inhibition and Inhibition/Switching), though not performance on other executive function tasks. Further, groups with reliably Improved, Worsened, or Chronic PTSD symptoms demonstrated significant differences in baseline inhibitory control and lifetime drinking history, with marked drinking differences starting in the early-to-mid 20s. We also found that PTSD symptom ch...
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Abstract: This study examined the performance of veterans and active duty personnel who served in Operation Enduring Freedom and/or Operation Iraqi Freedom (OEF/OIF) on a basic associative learning task. Eighty-eight individuals... more
Abstract: This study examined the performance of veterans and active duty personnel who served in Operation Enduring Freedom and/or Operation Iraqi Freedom (OEF/OIF) on a basic associative learning task. Eighty-eight individuals participated in this study. All received a comprehensive clinical evaluation to determine the presence and severity of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). The eyeblink conditioning task was composed of randomly intermixed delay and trace conditioned stimulus (CS) and unconditioned stimulus (US) pairs (acquisition) followed by a series of CS only trials (extinction). Results revealed that those with a clinical diagnosis of PTSD or a diagnosis of PTSD with comorbid mTBI acquired delay and trace conditioned responses (CRs) to levels and at rates similar to a deployed control group, thus suggesting intact basic associative learning. Differential extinction impairment was observed in the two clinical
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BackgroundA major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes... more
BackgroundA major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures.MethodsIn a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition.ResultsAt the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specificall...
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Research Interests: Psychology, Cognitive Science, Neuroimaging, Magnetic Resonance Imaging, Medicine, and 15 moreLinear models, Hippocampus, Humans, Female, Male, Three Dimensional Imaging, Clinical Sciences, Adult, Genetic Polymorphism, Cross Sectional Studies, Neurosciences, Neuroscience and Psychiatry, Hippocampal formation, Severity of Illness Index, and Psychiatric Status Rating Scales
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Research Interests: Neuroscience, Psychology, Cognitive Science, Magnetic Resonance Imaging, Medicine, and 15 moreEmotions, Brain Mapping, Brain, Humans, Functional Magnetic Resonance Imaging, Female, Male, Middle Aged, Rest, Adult, Human Brain Mapping, Disinhibition, Neurosciences, Frontal Lobe, and Neuropsychological Tests
Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) in military personnel is increasing dramatically following the OEF/OIF conflicts and is associated with alterations to brain structure. The present study examined... more
Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) in military personnel is increasing dramatically following the OEF/OIF conflicts and is associated with alterations to brain structure. The present study examined the relationship between PTSD and cortical thickness, and its possible modification by mTBI, in a 104-subject OEF/OIF veteran cohort ranging in age from 20 to 62 years. For each participant, two T1-weighted scans were averaged to create high-resolution images for calculation of regional cortical thickness. PTSD symptoms were assessed using the Clinician Administered PTSD Scale (CAPS) and scores were derived based on the previous month's symptoms ("current") and a Cumulative Lifetime Burden of PTSD (CLB-P) reflecting the integral of CAPS scores across the lifetime. Mild TBI was diagnosed using the Boston Assessment of TBI-Lifetime (BAT-L). Results demonstrated a clear negative relationship between current PTSD severity and thickness in...
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Hemi-spatial neglect is a disabling, neuropsychological impairment that restricts the ability to attend to incoming information on one side space. Most frequently associated with a lesion to the right hemisphere, the disorder is strongly... more
Hemi-spatial neglect is a disabling, neuropsychological impairment that restricts the ability to attend to incoming information on one side space. Most frequently associated with a lesion to the right hemisphere, the disorder is strongly predictive of general functional recovery from stroke. Although the standard therapy is of limited effectiveness, pilot studies indicate that more effective treatments may follow. Interest in these new potential treatments is, however, beginning to wane as few have progressed to the stage of randomised, controlled clinical trials. In this brief commentary, we point out that the absence of trials data not only reflects the preliminary nature of new treatments, but also the practical difficulties associated with meeting the target enrolment figures of large-scale trials. These problems have likewise slowed the development of treatments for other cognitive disorders. We suggest ways in which this problem may be overcome.
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Although most cases of acquired prosopagnosia are accompanied by bilateral brain lesions, a number also arise following right unilateral lesions. The prevailing consensus is that right hemisphere damage disrupts the configural... more
Although most cases of acquired prosopagnosia are accompanied by bilateral brain lesions, a number also arise following right unilateral lesions. The prevailing consensus is that right hemisphere damage disrupts the configural apprehension of faces, which in turn forces a reliance on part-based processing. Here we describe a patient who following right hemisphere damage is not only unable to apprehend the configural aspects of faces, but is also unable to apprehend their component parts when these are presented within a whole, upright face. Intriguingly, the patient is able to apprehend face parts when these are presented in isolation, within inverted faces, or in unfamiliar, scrambled arrangements. Furthermore, the patient can make use of configural information to detect local changes in non-face stimuli. The findings uncover a hitherto unreported form of impairment following right unilateral damage, and raise questions about the role of the left hemisphere in processing local information.
Research Interests: Cognitive Psychology, Cognitive Science, Cognition, Magnetic Resonance Imaging, Laterality, and 15 moreFace, Medicine, Information Processing, Humans, Cerebral Cortex, Male, Aged, Inversion, Analysis of Variance, Bf, Apprehension, Left Hemisphere, Cognition disorders, Functional Laterality, and Brain injuries
Research Interests: Neuroscience, Psychology, Computer Science, Principal Component Analysis, Magnetic Resonance Imaging, and 14 moreIndependent Component Analysis, Medicine, Brain Mapping, Humans, Cerebellum, Cerebral Cortex, Female, Neuroimage, Male, Young Adult, Rest, Neural pathways, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Psychology, Perception, Audiology, Face, Face recognition (Psychology), and 15 moreMedicine, Face perception, Vestibular System, Vision, Humans, Male, The, Middle Aged, Bf, X ray Computed Tomography, Galvanic Vestibular Stimulation, Psychomotor Performance, Neuropsychological Tests, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Geriatrics, Gerontology, Pain, Cognition, Aging, and 15 morePhysical Activity, Public Health, Cardiovascular disease, Medicine, Executive Function, Humans, Female, Male, MEASUREMENTS, Aged, Community Health and Preventive Medicine, Physical Exercise, Cross Sectional Studies, Motor activity, and Medical and Health Sciences
Research Interests: Psychology, Psychometrics, Traumatic Brain Injury, Medicine, Humans, and 15 moreBiomedical Research, Iraq War, Female, Male, Veterans, Young Adult, Boston, Middle Aged, Adult, Reproducibility of Results, Cross Sectional Studies, Brain injuries, Neuropsychological Tests, Psychology and Cognitive Sciences, and Medical and Health Sciences
ObjectiveThe purpose of this study was to evaluate the performance on the Clock‐in‐the‐Box (CIB), a screening measure for cognitive function, relative to neuropsychological testing in an older population with cardiovascular risk.MethodsA... more
ObjectiveThe purpose of this study was to evaluate the performance on the Clock‐in‐the‐Box (CIB), a screening measure for cognitive function, relative to neuropsychological testing in an older population with cardiovascular risk.MethodsA prospective cohort of older patients (>50 years) with cardiovascular risk was recruited to perform the CIB and complete a brief neuropsychological battery consisting of Trailmaking tests, the Hopkins Verbal Learning Test (HVLT), and fluency tasks. Performance on the CIB was scored according to standard criteria (range 0–8, 0–worst). The performance on the total CIB, working memory subscale (CIB–WM), and planning/organization (COB–PO) was compared to neuropsychological measures.ResultsThe cohort (n = 127) was older (age 67 ± 7 years) and diverse with 33% female (n = 42) and 42% non‐white race (n = 53). Cardiac risk factors were prevalent: hypertension (83%), hyperlipidemia (74%), overweight (84%), diabetes (48%), prior cardiac disease (39%), and s...
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This study explored on-line processing of local syntactic dependencies in normal subjects and in Broca's and Wernicke's aphasics using a lexical decision paradigm. In addition, subjects performed a grammatically judgement... more
This study explored on-line processing of local syntactic dependencies in normal subjects and in Broca's and Wernicke's aphasics using a lexical decision paradigm. In addition, subjects performed a grammatically judgement task on the real word pairs used in the lexical decision tasks. Results of two experiments for normal subjects indicated different syntactic priming effects as a function of the type of local syntactic dependency. Word pairs that formed a single constituent phrase, i.e., a verb phrase, showed both facilitory and inhibitory effects, whereas word pairs that reflected local syntactic dependencies across a phrase boundary, i.e., pronoun verb, showed only inhibitory effects. Broca's aphasics failed to show facilitory effects when presented with word pairs forming a single constituent phrase but, similar to normals, did show inhibition when presented with word pairs that reflected local syntactic dependencies across a phrase boundary. In contrast, Wernicke's aphasics failed to show inhibitory effects in both experiments. The implications of these results for theories of language processing deficits in aphasia are considered.
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Objective:Neurovascular coupling may be involved in compensatory mechanisms responsible for preservation of gait speed in elderly people with cerebrovascular disease. Our study examines the association between neurovascular coupling in... more
Objective:Neurovascular coupling may be involved in compensatory mechanisms responsible for preservation of gait speed in elderly people with cerebrovascular disease. Our study examines the association between neurovascular coupling in the middle cerebral artery and gait speed in elderly individuals with impaired cerebral vasoreactivity.Methods:Twenty‐two fast and 20 slow walkers in the lowest quartile of cerebral vasoreactivity were recruited from the MOBILIZE Boston Study. Neurovascular coupling was assessed in bilateral middle cerebral arteries by measuring cerebral blood flow during the N‐Back task. Cerebral white matter hyperintensities were measured for each group using magnetic resonance imaging.Results:Neurovascular coupling was attenuated in slow compared to fast walkers (2.8%; 95% confidence interval [CI], −0.9 to 6.6 vs 8.2%; 95% CI, 4.7–11.8; p = 0.02). The odds ratio of being a slow walker was 6.4 (95% CI, 1.7–24.9; p = 0.007) if there was a high burden of white matter ...
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Research Interests: Neuroscience, Psychology, Brain Imaging, Magnetic Resonance Imaging, Medicine, and 15 moreHumans, Cerebral Cortex, Brain Computer Interfaces, Alcoholism, Female, Brain Based Learning, Male, Clinical Sciences, Aged, Middle Aged, Atrophy, Adult, Alcohol Addiction, Neurosciences, and Case Control Studies
Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable... more
Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI. Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction...
Research Interests: Psychology, Posttraumatic Stress Disorder (PTSD), Traumatic Brain Injury, Magnetic Resonance Imaging, Medicine, and 11 moreComorbidity, Biological Sciences, Biological Psychiatry, Brain, Humans, Iraq War, Veterans, Brain injuries, Severity of Illness Index, Psychology and Cognitive Sciences, and Medical and Health Sciences
OBJECTIVE It is increasingly recognized that trauma victims, particularly Veterans, have co-occurring psychological and physical conditions that impact cognition, especially the domains of sustained attention and executive functioning.... more
OBJECTIVE It is increasingly recognized that trauma victims, particularly Veterans, have co-occurring psychological and physical conditions that impact cognition, especially the domains of sustained attention and executive functioning. Although previous work has generally attempted to isolate the unique cognitive effects of common combat-related comorbidities, less work has been done to examine how these conditions co-occur, and whether unique cognitive signatures accompany certain clinical combinations. METHOD To address this gap, we examined how several deployment-related conditions were associated with performance on a well-validated measure of sustained attention (i.e., gradual onset continuous performance task [gradCPT]) and a battery of standard neuropsychological measures in 123 Veterans from the Translational Research Center for TBI and Stress Disorders. Initially, a Principal component analysis was conducted to investigate how comorbid conditions grouped together. RESULTS Several sustained attention measures from the gradCPT were differentially associated with four unique combinations of trauma-related pathology. Specifically, a somatic component representing the combination of current pain, sleep disturbance, and mild traumatic brain injury was associated with a higher rate of failures of attentional engagement. On the other hand, a comorbid posttraumatic stress disorder (PTSD) and mood disorder component (moodPTSD), as well as a substance use disorder component, were associated with higher rates of inhibitory control failures. Increased attentional instability was associated with moodPTSD as well as an anxiety disorder component. In contrast, the cognitive effects of deployment-related trauma were not observed on standard neuropsychological measures. CONCLUSION These findings suggest that unique combinations of trauma-related pathology have dissociable effects on sustained attentional control. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Our previous work demonstrates that reduced activation of the executive network is associated with slow walking speed in a cohort of older adults from the MOBILIZE Boston Study. However, the influence of underlying white matter integrity... more
Our previous work demonstrates that reduced activation of the executive network is associated with slow walking speed in a cohort of older adults from the MOBILIZE Boston Study. However, the influence of underlying white matter integrity on the activation of this network and walking speed is unknown. Thus, we used diffusion-weighted imaging and fMRI during an n-back task to assess associations between executive network structure, function, and walking speed. Whole-brain tract-based spatial statistics (TBSS) were used to identify regions of white matter microstructural integrity that were associated with walking speed. The integrity of these regions was then entered into multiple regression models to predict task performance and executive network activation during the n-back task. Among the significant associations of FA with walking speed, we observed the anterior thalamic radiation and superior longitudinal fasciculus were further associated with both n-back response speed and exec...
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Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes... more
Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders. One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes. A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG...
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This study investigated the relationship between close proximity to detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans. A total of 333 participants completed a comprehensive evaluation that included assessment of... more
This study investigated the relationship between close proximity to detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans. A total of 333 participants completed a comprehensive evaluation that included assessment of neuropsychological functions, psychiatric diagnoses and history of military and non-military brain injury. Participants were assigned to a Close-Range Blast Exposure (CBE) or Non-Close-Range Blast Exposure (nonCBE) group based on whether they had reported being exposed to at least one blast within 10 meters. Groups were compared on principal component scores representing the domains of memory, verbal fluency, and complex attention (empirically derived from a battery of standardized cognitive tests), after adjusting for age, education, PTSD diagnosis, sleep quality, substance abuse disorder, and pain. The CBE group showed poorer performance on the memory component. Rates of clinical impairment were significantly higher in the CBE group on select CVLT...
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To examine the cross-sectional relationship between chronic pain and complex attention in a population of community-living older adults. Prospective cross-sectional cohort study. Population-based Maintenance of Balance, Independent... more
To examine the cross-sectional relationship between chronic pain and complex attention in a population of community-living older adults. Prospective cross-sectional cohort study. Population-based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study II. Individuals aged 71 to 101 (N=354). Chronic pain was measured using the pain severity and interference subscales of the Brief Pain Inventory. Four subscales of the Test of Everyday Attention were used to measure domains of attention switching and selective, sustained, and divided attention. Before and after multivariable adjustment, pain severity was associated with poorer scores on measures of selective and sustained attention. Pain interference scores also were significantly inversely associated with selective attention. Chronic pain is associated with poorer performance in selective and sustained attention in community-dwelling older adults. Further research is needed to determine whether e...
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Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between... more
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock). Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age...
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Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease, including obesity, hypertension, dyslipidemia, and hyperglycemia. While sizable prior literature has examined associations between individual risk... more
Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease, including obesity, hypertension, dyslipidemia, and hyperglycemia. While sizable prior literature has examined associations between individual risk factors and quantitative measures of cortical thickness (CT), only very limited research has investigated such measures in MetS. Furthermore, the relative contributions of these risk factors to MetS-related effects on brain morphology have not yet been studied. The primary goal of this investigation was to examine how MetS may affect CT. A secondary goal was to explore the relative contributions of individual risk factors to regional alterations in CT, with the potential to identify risk factor combinations that may underlie structural changes. Eighteen participants with MetS (mean age = 59.78 years) were age-matched with 18 healthy control participants (mean age = 60.50 years). CT measures were generated from T1-weighted images and groups were contr...
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Aim: We examined concordance of methylation levels across the Illumina Infinium HumanMethylation450 BeadChip and the Infinium MethylationEPIC BeadChip. Methods: We computed the correlation for 145 whole blood DNA samples at each of the... more
Aim: We examined concordance of methylation levels across the Illumina Infinium HumanMethylation450 BeadChip and the Infinium MethylationEPIC BeadChip. Methods: We computed the correlation for 145 whole blood DNA samples at each of the 422,524 CpG sites measured by both chips. Results: The correlation at some sites was high (up to r = 0.95), but many sites had low correlation (55% had r
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Research suggests that posttraumatic stress disorder (PTSD) is associated with metabolic syndrome (MetS) and that PTSD-associated MetS is related to decreased cortical thickness. However, the role of genetic factors in these associations... more
Research suggests that posttraumatic stress disorder (PTSD) is associated with metabolic syndrome (MetS) and that PTSD-associated MetS is related to decreased cortical thickness. However, the role of genetic factors in these associations is unclear. This study evaluated contributions of polygenic obesity risk and PTSD to MetS and of MetS and polygenic obesity risk to cortical thickness. 196 white, non-Hispanic veterans of the wars in Iraq and Afghanistan underwent clinical diagnostic interviews, physiological assessments, and genome-wide genotyping; 168 also completed magnetic resonance imaging scans. Polygenic risk scores (PRSs) for obesity were calculated from results of a prior genome-wide association study (Speliotes et al., 2010) and PTSD and MetS severity factor scores were obtained. Obesity PRS (β=0.15, p=0.009) and PTSD (β=0.17, p=0.005) predicted MetS and interacted such that the association between PTSD and MetS was stronger in individuals with greater polygenic obesity ri...
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Many US veterans of Afghanistan and Iraq have multiple physical and psychiatric problems. A major focus of research has been on determining the effects of mild Traumatic Brain Injury (mTBI), but mTBI is rarely diagnosed in the absence of... more
Many US veterans of Afghanistan and Iraq have multiple physical and psychiatric problems. A major focus of research has been on determining the effects of mild Traumatic Brain Injury (mTBI), but mTBI is rarely diagnosed in the absence of co-occurring conditions such as blast exposure, post-traumatic stress disorder (PTSD), depression, substance abuse, etc. These potentially interactive psychological and physical conditions produce complex patterns of cognitive, psychological, and physical symptoms that impede civilian reintegration and complicate efficient and effective treatment planning. The Translational Research Center for TBI and Stress Disorders (TRACTS) has developed a multidisciplinary approach to the assessment of deployment trauma and its consequences in veterans of these wars. The prospective TRACTS longitudinal cohort study conducts state-of-the-art assessments in the domains of biomedical function, lifetime head trauma, psychological function encompassing deployment exp...
Research Interests: Adolescent, Medicine, Humans, Iraq War, United States, and 10 moreFemale, Male, Veterans, Young Adult, Boston, Clinical Sciences, Aged, Middle Aged, Longitudinal Studies, and Adult(Female, Male, Veterans, Young Adult, Boston, Clinical Sciences, Aged, Middle Aged, Longitudinal Studies, and Adult)
(Female, Male, Veterans, Young Adult, Boston, Clinical Sciences, Aged, Middle Aged, Longitudinal Studies, and Adult)
Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely... more
Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Meanage = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. Mo...
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Changes in cerebral blood flow velocity (CBF) in response to a cognitive task (task-related ΔCBF) have been shown by Transcranial Doppler ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown whether reduced... more
Changes in cerebral blood flow velocity (CBF) in response to a cognitive task (task-related ΔCBF) have been shown by Transcranial Doppler ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown whether reduced task-related ΔCBF is associated with reduced neural activity in specific brain regions, as measured by blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). We assessed the regional changes in neural activity associated with reduced middle cerebral artery (MCA) task-related ΔCBF to an executive task and slow walking speed in 67 community-dwelling older adults from the MOBILIZE Boston Study. Participants underwent walking assessments and TCD ultrasonography measures of MCA ΔCBF during the n-back task of executive function. A subset of participants (n = 27) completed the same task during fMRI. Individual BOLD activation maps for the n-back task were correlated with TCD measures and network-level averages were associated with TCD an...
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Despite the prevalence of blast injuries in recent overseas conflicts, our knowledge of their impact on neural health is lacking. We have recently published work demonstrating differences in functional magnetic resonance imaging (fMRI)... more
Despite the prevalence of blast injuries in recent overseas conflicts, our knowledge of their impact on neural health is lacking. We have recently published work demonstrating differences in functional magnetic resonance imaging (fMRI) connectivity that were specific to close-range blast exposure (CBE), as opposed to other prevalent military-related factors. Here, we replicate this finding in an independent sample of 135 Veterans, again finding that CBE, regardless of concussion, is predictive of persistent changes in brain physiology. Although there was weak overlap anatomically, in both samples the group differences could be described as spreading of anticorrelation. Using the combined sample, we now seek to identify likely mechanisms that could bring about this effect. We compared participants with (n=116) and without (n=153) CBE by analyzing two networks through group difference maps and correlation distributions to assess spatially homogenous and heterogeneous effects. As bound...
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Interpersonal early life trauma (I-ELT) is associated with a myriad of functional impairments in adulthood, increased risk of drug addiction, and neuropsychiatric disorders. While deficits in emotional regulation and amygdala functioning... more
Interpersonal early life trauma (I-ELT) is associated with a myriad of functional impairments in adulthood, increased risk of drug addiction, and neuropsychiatric disorders. While deficits in emotional regulation and amygdala functioning are well characterized, deficits in general cognitive functioning have also been documented. However, the neural underpinnings of cognitive dysfunction in adults with a history of I-ELT and the potential relationship between amygdala-based functional connectivity and behavioral performance are currently poorly understood. This study examined how I-ELT affects the cognitive and neural mechanisms supporting sustained attention. A total of 66 Veterans (18 with and 48 without a history of I-ELT) completed a nonemotional sustained attention task during functional MRI. The individuals with I-ELT showed significant impairments in sustained attention (i.e., higher error rates, greater response variability). This cohort exhibited increased amygdala functiona...
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Veterans from recent military conflicts frequently report persisting symptoms associated with concussion well beyond the expected period of recovery following mild traumatic brain injury. This study examined differences in the reporting... more
Veterans from recent military conflicts frequently report persisting symptoms associated with concussion well beyond the expected period of recovery following mild traumatic brain injury. This study examined differences in the reporting of symptoms associated with concussion between clinical and research contexts. This naturalistic comparison included 91 Veterans from Operations Enduring Freedom (OEF), Iraqi Freedom (OIF) and New Dawn (OND). All participants were enrolled in a longitudinal study focused on traumatic brain injury and stress-related disorders and had also completed a VHA Comprehensive TBI Evaluation. Individuals completed the Neurobehavioral Symptom Inventory (NSI) during their research and clinical evaluations; additional measures of performance and symptom validity were also available for a subset of participants. NSI mean total and subscale scores were significantly higher when assessed in the clinical compared to the research setting, irrespective of the order and...
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Research Interests: Cognition, Aging, Medicine, Activities of Daily Living, Humans, and 15 moreHospitalization, Female, Male, Risk factors, Clinical Sciences, Aged, Middle Aged, Odds ratio, Risk Factors, Logistic Models, Psychiatric Status Rating Scales, Neuropsychological Tests, Cognitive dysfunction, Patient discharge, and mass Screening
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Early life trauma (ELT) has been shown to impair affective control and attention well into adulthood. Neuroimaging studies have further shown that ELT was associated with decreased white matter integrity in the prefrontal areas in... more
Early life trauma (ELT) has been shown to impair affective control and attention well into adulthood. Neuroimaging studies have further shown that ELT was associated with decreased white matter integrity in the prefrontal areas in children and adults. However, no study to date has looked at the relationship between white matter integrity and affective control in individuals with and without a history of ELT. To examine this, we tested 240 Veterans with (ELT N = 80) and without (NoELT N = 160) a history of childhood sexual abuse, physical abuse or family violence. Affective control was measured with the Affective Go/No-Go (AGN) and attention was indexed with the Test of Variable Attention (TOVA). White matter integrity was measured using fractional anisotropy (FA). Results showed greater number of errors on the AGN in ELT compared to NoELT. There was no difference on the TOVA. While there were no mean differences in FA, there was an interaction between FA and reaction time to positiv...
Research Interests: Psychology, Emotional intelligence, Magnetic Resonance Imaging, Attention, Medicine, and 15 moreExecutive Function, Brain, Humans, Female, Male, Reaction Time, Cluster Analysis, Adult, Psychiatric, Cohort Studies, Psychiatric Status Rating Scales, Neuropsychological Tests, Surveys and Questionnaires, Psychology and Cognitive Sciences, and Medical and Health Sciences
We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained... more
We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological func...
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Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common among US veterans of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND). We postulated that these injuries may... more
Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common among US veterans of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND). We postulated that these injuries may modulate pain processing in these individuals and affect their subjective pain levels. Cross-sectional. 310 deployed service members of OEF/OIF/OND without a lifetime history of moderate or severe TBI were included in this study. All participants completed a comprehensive evaluation for Blast Exposure, mTBI, PTSD, and Pain Levels. The Boston Assessment of TBI-Lifetime Version (BAT-L) was used to assess blast exposure and potential brain injury during military service. The Clinician-Administered PTSD Scale (CAPS) characterized presence and severity of PTSD. The Visual Analog Scale (VAS) was used to assess pain intensity over the previous month before the interview, with higher scores indicative of worse pain. Statistical analysis was performed by ANOVA and ...
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While the associations between psychological distress (e.g., posttraumatic stress disorder [PTSD], depression) and sleep dysfunction have been demonstrated in trauma-exposed populations, studies have not fully explored the associations... more
While the associations between psychological distress (e.g., posttraumatic stress disorder [PTSD], depression) and sleep dysfunction have been demonstrated in trauma-exposed populations, studies have not fully explored the associations between sleep dysfunction and the wide range of common physical and physiological changes that can occur after trauma exposure (e.g., pain, cardiometabolic risk factors). We aimed to clarify the unique associations of psychological and physical trauma sequelae with different aspects of self-reported sleep dysfunction. A comprehensive psychological and physical examination was administered to 283 combat-deployed trauma-exposed Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans. The Pittsburgh Sleep Quality Index (PSQI) and PSQI Addendum for PSTD (PSQI-A) were administered along with measures of PTSD, depression, anxiety, pain, traumatic brain injury, alcohol use, nicotine dependence, and cardiometabolic symptom...
Research Interests:
Research Interests:
The frequent co-occurrence of antisocial behavior and other disinhibited phenotypes reflects a highly heritable externalizing spectrum. We examined the molecular genetic basis of this spectrum by testing polygenic associations with... more
The frequent co-occurrence of antisocial behavior and other disinhibited phenotypes reflects a highly heritable externalizing spectrum. We examined the molecular genetic basis of this spectrum by testing polygenic associations with psychopathology symptoms, impulsive traits, and cognitive functions in two samples of primarily military veterans ( n = 537, n = 194). We also investigated whether polygenic risk for externalizing moderated the effects of trauma on these phenotypes. As hypothesized, polygenic risk positively predicted externalizing psychopathology and negatively predicted performance on inhibitory control tasks. Gene-by-environment effects were also evident, with trauma exposure predicting greater impulsivity and less working memory capacity, but only at high levels of genetic liability. As expected, polygenic risk was not associated with internalizing psychopathology or episodic memory performance. This is the first independent replication of the polygenic score as a mea...
Research Interests:
Chronic Pain (CP) has been associated with changes in gray matter integrity in the cingulate and insular cortex. However, these changes have not been studied in Veterans, despite high prevalence rates of CP and interactions with... more
Chronic Pain (CP) has been associated with changes in gray matter integrity in the cingulate and insular cortex. However, these changes have not been studied in Veterans, despite high prevalence rates of CP and interactions with combat-derived disorders. In the current study, 54 Veterans with a history of CP and 103 Veterans without CP were recruited from the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS). Cortical thickness from structural MRI scans was determined using the FreeSurfer software package. Results showed that Veterans with CP showed a negative association between cortical thickness and levels of combat exposure in the left inferior frontal gyrus and superior parietal cortex, as well as the right rostral middle frontal gyrus, precentral and postcentral gyri and the superior temporal cortex. These findings suggest that CP may alter the relationship between cortical thickness and exposure to the stress of combat.
Research Interests: Cognitive Science, Psychiatry, Chronic Pain, Magnetic Resonance Imaging, Medicine, and 15 moreTemporal Lobe, Humans, Cerebral Cortex, United States, Female, Male, Veterans, Clinical Sciences, Adult, Parietal Lobe, Neurosciences, Frontal Lobe, Case Control Studies, Psychology and Cognitive Sciences, and Medical and Health Sciences
Metabolic syndrome (MetS), defined by a constellation of cardiometabolic pathologies, is highly prevalent among veterans, especially veterans with posttraumatic stress disorder (PTSD), and poses a major risk for adverse health outcomes,... more
Metabolic syndrome (MetS), defined by a constellation of cardiometabolic pathologies, is highly prevalent among veterans, especially veterans with posttraumatic stress disorder (PTSD), and poses a major risk for adverse health outcomes, including neurodegeneration and mortality. Given this, we evaluated 1) the association between MetS and neural integrity, indexed by cortical thickness; 2) the relationship between PTSD and MetS; and 3) whether PTSD was associated with cortical thickness indirectly through MetS. The sample consisted of 346 US military veterans (89.3% male; 71.4% white) who deployed to Iraq, Afghanistan, or both. Neuroimaging data were available for 274 participants. In whole-brain analyses, MetS was negatively associated with cortical thickness in two left and four right hemisphere regions, as follows: bilateral temporal lobe, including temporal pole, fusiform gyrus, and insula, and extending into occipital cortex (left hemisphere) and orbitofrontal cortex (right hemisphere); bilateral precuneus, posterior cingulate, calcarine, and occipital-parietal cortex; and right rostral anterior cingulate cortex and central sulcus/postcentral gyrus. Path models showed that PTSD predicted MetS (β = .19, p < .001), which was associated with reduced cortical thickness (β = -.29 to -.43, all p < .001). Results from this young veteran sample provide evidence that PTSD confers risk for cardiometabolic pathology and neurodegeneration and raise concern that this cohort may be aging prematurely and at risk for substantial medical and cognitive decline. This study highlights the need to identify the molecular mechanisms linking PTSD to MetS and effective interventions to reduce PTSD-related health comorbidities.