Neuroimaging Research for Veterans Center

VA, United States

Neuroimaging Research for Veterans Center

VA, United States
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News Article | December 5, 2016
Site: www.eurekalert.org

(Boston)--Over the past decade, researchers have learned that the hippocampus--historically known for its role in forming memories--is involved in much more than just remembering the past; it plays an important role in imagining events in the future. Yet, scientists still do not know precisely how the hippocampus contributes to episodic imagining--until now. Researchers from Boston University School of Medicine (BUSM) have determined the role of the hippocampus in future imaging lies in the process of constructing a scene in one's mind. The findings, which appear in the journal Cerebral Cortex, shed important light on how the brain supports the capacity to imagine the future and pinpoints the brain regions that provide the critical ingredients for performing this feat. The hippocampus is affected by many neurological conditions and diseases and it also can be compromised during normal aging. Future thinking is a cognitive ability that is relevant to all humans. It is needed to plan for what lies ahead, whether to navigate daily life or to make decisions for major milestones further in the future. Using functional Magnetic Resonance Imaging, BUSM researchers performed brain scans on healthy adults while they were imagining events. They then compared brain activity in the hippocampus when participants answered questions pertaining to the present or the future. After that, they compared brain activity when participants answered questions about the future that did or did not require imagining a scene. "We observed no differences in hippocampal activity when we compared present versus future imaging, but we did observe stronger activity in the hippocampus when participants imagined a scene compared to when they did not, suggesting a role for the hippocampus in scene construction but not mental time travel," explained corresponding author Daniela Palombo, PhD, postdoctoral fellow in the memory Disorders Research Center at BUSM and at the VA Boston Healthcare System. According to the researchers the importance of studying how the hippocampus contributes to cognitive abilities is bolstered by the ubiquity of hippocampal involvement in many conditions. "These findings help provide better understanding of the role of the hippocampus in future thinking in the normal brain, and may eventually help us better understand the nature of cognitive loss in individuals with compromised hippocampal function," she added. Palombo believes that once knowledge about which aspects of future imagining are and are not dependent on the hippocampus, targeted rehabilitation strategies can be designed that exploit those functions that survive hippocampal dysfunction and may provide alternate routes to engage in future thinking. Funding for this study was provided by the National Institutes of Mental Health (grant number H093431) and the Department of Veterans Affairs (Clinical Science Research and Development Service and Rehabilitation Research & Development Service grant number E7822W). Co-author D.J.P. was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR). This work was further supported with resources and the use of facilities at the Neuroimaging Research for Veterans Center, VA Boston Healthcare System.


Spielberg J.M.,Neuroimaging Research for Veterans Center | Spielberg J.M.,Boston University | Miller G.A.,University of California at Los Angeles | Miller G.A.,University of Illinois at Urbana - Champaign | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The ability to inhibit distracting stimuli from interfering with goaldirected behavior is crucial for success in most spheres of life. Despite an abundance of studies examining regional brain activation, knowledge of the brain networks involved in inhibitory control remains quite limited. To address this critical gap, we applied graph theory tools to functionalmagnetic resonance imaging data collected while a large sample of adults (n = 101) performed a color-word Stroop task. Higher demand for inhibitory control was associated with restructuring of the global network into a configuration that was more optimized for specialized processing (functional segregation), more efficient at communicating the output of such processing across the network (functional integration), and more resilient to potential interruption (resilience). In addition, there were regional changes with right inferior frontal sulcus and right anterior insula occupying more central positions as network hubs, and dorsal anterior cingulate cortex becoming more tightly coupled with its regional subnetwork. Given the crucial role of inhibitory control in goal-directed behavior, present findings identifying functional network organization supporting inhibitory control have the potential to provide additional insights into how inhibitory control may break down in a wide variety of individuals with neurological or psychiatric difficulties.


Coutu J.-P.,Harvard University | Coutu J.-P.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology | Chen J.J.,Harvard University | Chen J.J.,Rotman Research Institute | And 3 more authors.
Neurobiology of Aging | Year: 2014

Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate "diffusion footprint", or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease. © 2014 Elsevier Inc.


Dumas A.,Massachusetts General Hospital | Dierksen G.A.,Massachusetts General Hospital | Gurol M.E.,Massachusetts General Hospital | Halpin A.,Massachusetts General Hospital | And 8 more authors.
Annals of Neurology | Year: 2012

Objective: In addition to its role in hemorrhagic stroke, advanced cerebral amyloid angiopathy (CAA) is also associated with ischemic lesions and vascular cognitive impairment. We used functional magnetic resonance imaging (MRI) techniques to identify CAA-associated vascular dysfunction. Methods: Functional MRI was performed on 25 nondemented subjects with probable CAA (mean ± standard deviation age, 70.2 ± 7.8 years) and 12 healthy elderly controls (age, 75.3 ± 6.2 years). Parameters measured were reactivity to visual stimulation (quantified as blood oxygen level-dependent [BOLD] response amplitude, time to peak response, and time to return to baseline after stimulus cessation) and resting absolute cerebral blood flow in the visually activated region (measured by arterial spin labeling). Results: CAA subjects demonstrated reduced response amplitude (percentage change in BOLD signal, 0.65 ± 0.28 vs 0.89 ± 0.14; p < 0.01), prolonged time to peak (11.1 ± 5.1 vs 6.4 ± 1.8 seconds; p < 0.001), and prolonged time to baseline (16.5 ± 6.7 vs 11.6 ± 3.1 seconds; p < 0.001) relative to controls. These differences were independent of age, sex, and hypertension in multivariable analysis and were also present in secondary analyses excluding nonresponsive voxels or voxels containing chronic blood products. Within the CAA group, longer time to peak correlated with overall volume of white matter T2 hyperintensity (Pearson correlation, 0.53; p = 0.007). Absolute resting blood flow in visual cortex, in contrast, was essentially identical between the groups (44.0 ± 12.6 vs 45.0 ± 10.0ml/100g/min, p = 0.8). Interpretation: Functional MRI identifies robust differences in both amplitude and timing of the response to visual stimulation in advanced CAA. These findings point to potentially powerful approaches for identifying the mechanistic links between vascular amyloid deposits, vascular dysfunction, and CAA-related brain injury. © 2012 American Neurological Association.


Salat D.H.,Massachusetts General Hospital | Salat D.H.,Neuroimaging Research for Veterans Center
Neuroscience | Year: 2014

Alterations in cerebrovascular structure and function may underlie the most common age-associated cognitive, psychiatric, and neurological conditions presented by older adults. Although much remains to understand, existing research suggests several age-associated detrimental conditions may be mediated through sometimes subtle small vessel-induced damage to the cerebral white matter. Here we review a selected portion of the vast work that demonstrates links between changes in vascular and neural health as a function of advancing age, and how even changes in low-to-moderate risk individuals, potentially beginning early in the adult age-span, may have an important impact on functional status in late life. © 2013 .


Hayes S.M.,Boston University | Hayes S.M.,Neuroimaging Research for Veterans Center | Alosco M.L.,Boston University | Alosco M.L.,Kent State University | And 2 more authors.
Current Geriatrics Reports | Year: 2014

Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns. © 2014 Springer Science+Business Media New York (outside the USA).


Alosco M.L.,Boston University | Alosco M.L.,Kent State University | Hayes S.M.,Boston University | Hayes S.M.,Neuroimaging Research for Veterans Center
Heart Failure Reviews | Year: 2015

Cardiovascular disease is a recognized contributor to the pathogenesis of Alzheimer’s disease (AD). Heart failure (HF) is a cardiovascular subtype that can be used to model the contribution of cardiovascular disease to AD. Neuroimaging research indicates that HF patients exhibit a diverse range of structural brain alterations and epidemiological studies suggest HF may be an important risk factor for AD. The neural alterations observed in HF may overlap with those observed in AD and contribute to increased risk of AD in HF patients. To examine this possibility, we reviewed structural MRI studies in persons with HF. We examined subcortical brain regions affected in the early stages of AD (medial temporal lobes), as well as cortical alterations that typically occur in the later stages of AD. Our review indicates that patients with HF exhibit greater neural atrophy and white matter microstructural alterations of nearly every region of the Papez circuit (e.g., hippocampus, cingulate gyrus, thalamus, mammillary bodies, and fornix), as well-significant alterations in cortical and cerebellar regions. Based on animal research and past work in AD patients, the mechanisms for structural brain changes in HF may stem from reductions in cerebral blood flow subsequent to cardiac deficiency. This review supports the hypothesis that HF may contribute to AD risk via widespread structural brain changes, including many of the same regions affected by AD. Case-controlled prospective neuroimaging studies with long-term follow-ups are needed to clarify the risk of AD in HF and elucidate the neural underpinnings of AD risk in HF. © 2015, Springer Science+Business Media New York (outside the USA).


Hayes S.M.,Boston University | Hayes S.M.,Neuroimaging Research for Veterans Center | Hayes J.P.,Boston University | Hayes J.P.,National Center for Posttraumatic Stress Disorder | And 2 more authors.
Frontiers in Aging Neuroscience | Year: 2013

The literature examining the relationship between cardiorespiratory fitness and the brain in older adults has increased rapidly, with 30 of 34 studies published since 2008. Here we review cross-sectional and exercise intervention studies in older adults examining the relationship between cardiorespiratory fitness and brain structure and function, typically assessed using Magnetic Resonance Imaging (MRI). Studies of patients with Alzheimer's disease are discussed when available. The structural MRI studies revealed a consistent positive relationship between cardiorespiratory fitness and brain volume in cortical regions including anterior cingulate, lateral prefrontal, and lateral parietal cortex. Support for a positive relationship between cardiorespiratory fitness and medial temporal lobe volume was less consistent, although evident when a region-of-interest approach was implemented. In fMRI studies, cardiorespiratory fitness in older adults was associated with activation in similar regions as those identified in the structural studies, including anterior cingulate, lateral prefrontal, and lateral parietal cortex, despite heterogeneity among the functional tasks implemented. This comprehensive review highlights the overlap in brain regions showing a positive relationship with cardiorespiratory fitness in both structural and functional imaging modalities. The findings suggest that aerobic exercise and cardiorespiratory fitness contribute to healthy brain aging, although additional studies in Alzheimer's disease are needed. © 2013 Hayes, Hayes, Cadden and Verfaellie.


Daselaar S.M.,Duke University | Daselaar S.M.,Donders Institute for Brain | Iyengar V.,Duke University | Davis S.W.,University of Cambridge | And 4 more authors.
Cerebral Cortex | Year: 2013

The reliable neuroimaging finding that older adults often show greater activity (over-recruitment) than younger adults is typically attributed to compensation. Yet, the neural mechanisms of over-recruitment in older adults (OAs) are largely unknown. Rodent electrophysiology studies have shown that as number of afferent fibers within a circuit decreases with age, the fibers that remain show higher synaptic field potentials (less wiring, more firing). Extrapolating to system-level measures in humans, we proposed and tested the hypothesis that greater activity in OAs compensates for impaired white-matter connectivity. Using a neuropsychological test battery, we measured individual differences in executive functions associated with the prefrontal cortex (PFC) and memory functions associated with the medial temporal lobes (MTLs). Using event-related functional magnetic resonance imaging, we compared activity for successful versus unsuccessful trials during a source memory task. Finally, we measured white-matter integrity using diffusion tensor imaging. The study yielded 3 main findings. First, low-executive OAs showed greater success-related activity in the PFC, whereas low-memory OAs showed greater success-related activity in the MTLs. Second, low-executive OAs displayed white-matter deficits in the PFC, whereas low-memory OAs displayed white-matter deficits in the MTLs. Finally, in both prefrontal and MTL regions, white-matter decline and success-related activations occurred in close proximity and were negatively correlated. This finding supports the less-wiring-more-firing hypothesis, which provides a testable account of compensatory over-recruitment in OAs. © The Author 2013. Published by Oxford University Press.


Chen J.J.,Rotman Research Institute | Chen J.J.,Harvard University | Rosas H.D.,Harvard University | Salat D.H.,Harvard University | Salat D.H.,Neuroimaging Research for Veterans Center
PLoS ONE | Year: 2013

Degeneration of cerebral white matter is commonly observed in aging, and the associated degradation in neural connectivity contributes to cognitive decline in older adults. Vascular dysfunction has been implicated as a potential mechanism for general age-related neural tissue deterioration; however, no prior study has examined the direct relationship between cortical vascular health and subcortical white-matter integrity. In this work, we aimed to determine whether blood supply to the brain is associated with microstructural integrity of connective tissue, and whether such associations are regionally specific and mainly accounted for by aging. We examined the association between cerebral blood flow (CBF) in the cortical mantle, measured using arterial spin labeling (ASL), and subcortical white-matter integrity, measured using diffusion tensor imaging (DTI), in a group of healthy adults spanning early to late adulthood. We found cortical CBF to be significantly associated with white-matter integrity throughout the brain. In addition, these associations were only partially tied to aging, as they remained even when statistically controlling for age, and when restricting the analyses to a young subset of the sample. Furthermore, vascular risk was not a prominent determinant of these effects. These findings suggest that the overall blood supply to the brain is an important indicator of white-matter health in the normal range of variations amongst adults, and that the decline in CBF with advancing age may potentially exacerbate deterioration of the connective anatomy of the brain. © 2013 Chen et al.

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