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1.  Regional homogeneity and resting state functional connectivity: associations with exposure to early life stress 
Psychiatry research  2013;214(3):10.1016/j.pscychresns.2013.07.013.
Early life stress (ELS) confers risk for psychiatric illness. Previous literature suggests ELS is associated with decreased resting-state functional connectivity (rs-FC) in adulthood, but there are no studies of resting-state neuronal activity in this population. This study investigated whether ELS-exposed individuals demonstrate resting-state activity patterns similar to those found in PTSD. Twenty-seven adults (14 with at least moderate ELS), who were medication-free and without psychiatric or medical illness, underwent MRI scans during two 4-minute rest periods. Resting-state activity was examined using regional homogeneity (ReHo), which estimates regional activation patterns through indices of localized concordance. ReHo values were compared between groups, followed by rs-FC analyses utilizing ReHo-localized areas as seeds to identify other involved regions. Relative to controls, ELS subjects demonstrated diminished ReHo in the inferior parietal lobule (IPL) and superior temporal gyrus (STG). ReHo values were inversely correlated with ELS severity. Secondary analyses revealed decreased rs-FC between the IPL and right precuneus/posterior cingulate, left fusiform gyrus, cerebellum and caudate in ELS subjects. These findings indicate that ELS is associated with altered resting-state activity and connectivity in brain regions involved in trauma-related psychiatric disorders. Future studies are needed to evaluate whether these associations represent potential imaging biomarkers of stress exposure.
PMCID: PMC3849340  PMID: 24090510
posttraumatic stress disorder; resting state activity; inferior parietal lobule; superior temporal gyrus
2.  Early Life Stress is Associated with Greater Default Network Deactivation During Working Memory in Healthy Controls: A Preliminary Report 
Brain imaging and behavior  2013;7(2):204-212.
Early life stress (ELS) is a common risk factor for psychopathology, but there are few functional neuroimaging studies investigating its effects. In this preliminary study, we investigated the correlates of ELS exposure on the default network (DN) through measurements of task-associated DN deactivation. Data were analyzed from 19 subjects without psychiatric illness (10 with ELS). Subjects performed the working memory (WM) N-back task (including a 2-back WM and 0-back control condition) while undergoing functional MRI. We compared brain responses in the two groups across 5 bilateral DN regions using an a priori region of interest (ROI) analysis. The ELS group demonstrated significantly greater DN deactivation, observed in the right posterior cingulate cortex PCC, bilateral medial prefrontal cortex, left middle/superior frontal gyrus and right middle temporal region. These preliminary results indicate subjects with ELS demonstrate greater DN deactivations to WM challenges compared to non-ELS controls, potentially reflecting a biomarker of long-term effects of ELS exposure.
PMCID: PMC3632656  PMID: 23269472
Early Life Stress; Default Network; Working Memory; Medial Prefrontal Cortex; FMRI
3.  Decreased Default Network Connectivity is Associated with Early Life Stress in Medication-Free Healthy Adults 
Early life stress (ELS) is a significant risk factor for psychopathology, although there are few functional imaging studies investigating its effects. Previous literature suggests that ELS is associated with changes in structure and function in the medial prefrontal cortex (MPFC), which forms the main anterior node of the default network (DN). This study investigated the impact of ELS history on resting state DN connectivity, using seed-based correlation analyses (SCA) involving the posterior cingulate cortex (PCC). Data were analyzed from 22 adult subjects without psychiatric or medical illness (13 with and 9 without ELS); none were taking psychotropic medication. Relative to controls, the ELS group had significant decreases in DN connectivity, observed between the PCC seed and the MPFC and inferior temporal cortex. Further analyses revealed a trend-level increase in connectivity between the amygdala and MPFC associated with ELS history. In conclusion, this study found that subjects with ELS, in the absence of psychiatric illness and medication exposure, demonstrated decreased DN connectivity, and trend-level increases in connectivity between the amygdala and MPFC. These findings suggest that altered resting state connectivity is a correlate of stress exposure, rather than a product of medication or psychiatric morbidity.
PMCID: PMC3581700  PMID: 23141153
Default Network; Early Life Stress; Resilience; Functional Connectivity; Post Traumatic Stress Disorder; Medial Prefrontal Cortex
4.  Brain response to food stimulation in obese, normal weight, and successful weight loss maintainers 
Obesity (Silver Spring, Md.)  2012;20(11):2220-2225.
As many people struggle with maintenance of weight loss, the study of successful weight loss maintainers (SWLM) can yield important insights into factors contributing to weight loss maintenance. However, little research has examined how SWLM differ from people who are obese or normal weight (NW) in brain response to orosensory stimulation. The goal of this study was to determine if SWLM exhibit different brain responses to orosensory stimulation. Brain response to one-minute orosensory stimulation with a lemon lollipop was assessed using functional magnetic resonance imaging (FMRI) among 49 participants, including SWLM (n=17), NW (n=18) and obese (n=14) controls. Significant brain responses were observed in nine brain regions, including the bilateral insula, left inferior frontal gyrus, left putamen, and other sensory regions. All regions also exhibited significant attenuation of this response over one minute. The SWLM exhibited greater response compared to the other groups in all brain regions. Findings suggest that the response to orosensory stimulation peaks within 40 seconds and attenuates significantly between 40-60 seconds in regions associated with sensation, reward, and inhibitory control. Greater reactivity among the SWLM suggests that greater sensory reactivity to orosensory stimulation, increased anticipated reward, and subsequently greater inhibitory processing are associated with weight loss maintenance.
PMCID: PMC3483466  PMID: 22569002
Functional Magnetic Resonance Imaging; Functional Neuroimaging; Weight Loss Maintenance
5.  Cerebrovascular Perfusion among Older Adults is Moderated by Strength Training and Gender 
Neuroscience letters  2013;560:26-30.
Cerebral perfusion is important in older adults as it is linked to cognitive declines. Physical activity can improve blood flow in the body but little is known about the relationship between physical activity and cerebral perfusion in older adults. In particular, no study has investigated the relation between strength training and cerebral perfusion. We examined whether different types of physical activity (assessed with the Rapid Assessment of Physical Activity questionnaire) were associated with MRI cerebrovascular perfusion in 59 older adults. There was a significant interaction between gender and strength training, such that women who engaged in strength training (weight lifting or calisthenics) at least once per week exhibited significantly greater cerebrovascular perfusion than women who did not. This interaction remained significant after controlling for other physical activity, demographics, and health variables. These findings suggest that regular strength training can be beneficial for cerebrovascular health in women.
PMCID: PMC3920729  PMID: 24355360
cerebral perfusion; strength training; sex; physical activity; ASL
7.  Left Atrial Size is Independently Associated with Cognitive Function 
Left atrial (LA) diameter is easily attainable from echocardiograph and sensitive to underlying cardiovascular disease severity, though its association with neurocognitive outcomes is not well understood. Fifty older adults (64.50 ± 9.41 years) recruited from outpatient cardiology clinics and local papers underwent magnetic resonance imaging (MRI), were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and completed psychosocial self-report measures. LA diameter was quantified using echocardiogram. Hierarchical regression analyses revealed greater LA size was independently associated with reduced performance on the following RBANS composites: language, delayed memory, and total index (p < .05 for all). Hierarchical regression analysis demonstrated no significant association between LA diameter and whole brain volume (p > .05). The current study suggests that greater LA size is associated with cognitive dysfunction in older adults and prospective studies are needed to validate these findings and elucidate underlying mechanisms.
PMCID: PMC4166650  PMID: 23394115
Left Atrial Diameter; Cognitive Function; Cardiovascular Disease; Echocardiogram; Neuroimaging; Cerebrovascular disease
8.  The Interactive Effects of Cerebral Perfusion and Depression on Cognitive Function in Older Adults with Heart Failure 
Psychosomatic medicine  2013;75(7):632-639.
Depression is common among persons with heart failure (HF) and has been linked to cognitive impairment in this population. The mechanisms of this relationship are unclear, and the current study examined whether cerebral perfusion moderates the association between depressive symptomatology and cognitive impairment in patients with HF.
Persons with HF (N=89; 67.61 (SD = 11.78) years of age) completed neuropsychological testing and impedance cardiography. Depressive symptomatology was assessed using the Beck Depression Inventory-II and transcranial doppler was used to quantify cerebral perfusion.
Depression was associated with reduced performance on tasks assessing attention/executive function (r=−0.28), language (r=−.0.30) and motor function (r=−.28) in unadjusted models (p-values < 0.05). Global cerebral blood flow was correlated with memory performance (r=0.22, p=.040) but not to other tasks. A moderation analysis was performed using hierarchical regression models for attention/executive function, memory, language, and motor function. For each model, medical and demographic characteristics were entered into the initial blocks, and the final block consisted of an interaction term between global cerebral blood flow velocity (CBF-V) and the BDI-II. The interaction between greater depressive symptomatology and decreased global CBF-V was associated with greater deficits in attention/executive function (β = .32, ΔR2 = .08, p = .003).
Depressive symptomatology and cerebral hypoperfusion interact to adversely affect cognitive performance in older adults with HF. Longitudinal studies are needed to clarify this relationship and elucidate subsequent neuropathology.
PMCID: PMC3770733  PMID: 23873714
Cognitive impairment; Cerebral Perfusion; Heart failure; Depression; Cardiovascular disease; Cerebral blood flow velocity
9.  Independent and Interactive Effects of Blood Pressure and Cardiac Function on Brain Volume and White Matter Hyperintensities in Heart Failure 
Reduced systemic perfusion and comorbid medical conditions are key contributors to adverse brain changes in heart failure (HF). Hypertension, the most common co-occurring condition in HF, accelerates brain atrophy in aging populations. However, the independent and interactive effects of blood pressure and systemic perfusion on brain structure in HF have yet to be investigated.
Forty-eight older adults with HF underwent impedance cardiography to assess current systolic blood pressure status, and cardiac index to quantify systemic perfusion. All participants underwent brain magnetic resonance imaging to quantify total brain, total and subcortical gray matter volume, and white matter hyperintensities (WMH) volume.
Regression analyses adjusting for medical and demographic factors showed decreased cardiac index was associated with smaller subcortical gray matter volume (p < .01) and higher systolic blood pressure predicted reduced total gray matter volume (p = .03). The combination of higher blood pressure and lower cardiac index exacerbated WMH (p = .048).
Higher blood pressure and systemic hypoperfusion are associated with smaller brain volume and these factors interact to exacerbate WMH in HF. Prospective studies are needed to clarify the effects of blood pressure on the brain in HF, including the role of long-term blood pressure fluctuations.
PMCID: PMC3770819  PMID: 23735419
Blood pressure; brain; cognition; heart failure; cardiac index; MRI
10.  Cerebral Perfusion is Associated with White Matter Hyperintensities in Older Adults with Heart Failure 
Cognitive impairment is common in heart failure (HF) and believed to be the result of cerebral hypoperfusion and subsequent brain changes including white matter hyperintensities (WMH). The current study examined the association between cerebral blood flow and WMH in HF patients and the relationship of WMH to cognitive impairment. Sixty-nine patients with HF completed the mini mental state examination (MMSE), echocardiogram, transcranial Doppler sonography (TCD) for cerebral blood flow velocity of the middle cerebral artery and brain magnetic resonance imaging (MRI). Multivariable hierarchical regression analyses controlling for medical and demographic characteristics as well as intracranial volume showed reduced cerebral blood flow velocity of the middle cerebral artery was associated with greater WMH (β = −.34, p = .02). Follow up regression analyses adjusting for the same medical and demographic factors in addition to cerebral perfusion also revealed marginal significance between increased WMH and poorer performance on the MMSE (β = −.26, p = .05). This study suggests that reduced cerebral perfusion is associated with greater WMH in older adults with HF. Our findings support the widely proposed mechanism of cognitive impairment in HF patients and prospective studies are needed to confirm our findings.
PMCID: PMC3692594  PMID: 23517434
Cardiovascular disease; cerebral blood flow; cognitive function; heat failure; white matter hyperintensities
11.  Dissociable Brain Signatures of Choice Conflict and Immediate Reward Preferences in Alcohol Use Disorders 
Addiction biology  2012;10.1111/adb.12017.
Impulsive delayed reward discounting (DRD) is an important behavioral process in alcohol use disorders (AUDs), reflecting incapacity to delay gratification. Recent work in neuroeconomics has begun to unravel the neural mechanisms supporting DRD, but applications of neuroeconomics in relation to AUDs have been limited. This study examined the neural mechanisms of DRD preferences in AUDs, with emphasis on dissociating activation patterns based on DRD choice type and level of cognitive conflict. Heavy drinking adult males with (n = 13) and without (n = 12) a diagnosis of an AUD completed a monetary DRD task during a functional magnetic resonance imaging scan. Participant responses were coded based on choice type (impulsive vs. restrained) and level of cognitive conflict (easy vs. hard). AUD+ participants exhibited significantly more impulsive DRD decision-making. Significant activation during DRD was found in several decision-making regions, including dorsolateral prefrontal cortex (DLPFC), insula, posterior parietal cortex (PPC), and posterior cingulate. An axis of cognitive conflict was also observed, with hard choices associated with anterior cingulate cortex and easy choices associated with activation in supplementary motor area. AUD+ individuals exhibited significant hyperactivity in regions associated with cognitive control (DLPFC) and prospective thought (PPC) and exhibited less task-related deactivation of areas associated with the brain's default network during DRD decisions. This study provides further clarification of the brain systems supporting DRD in general and in relation to AUDs.
PMCID: PMC3871988  PMID: 23231650
Alcohol use disorders; delay discounting; neuroeconomics
12.  Poorer Physical Fitness is Associated with Reduced Structural Brain Integrity in Heart Failure 
Physical fitness is an important correlate of structural and functional integrity of the brain in healthy adults. In heart failure (HF) patients, poor physical fitness may contribute to cognitive dysfunction and we examined the unique contribution of physical fitness to brain structural integrity among patients with HF.
Sixty-nine HF patients performed the Modified Mini Mental State examination (3MS) and underwent brain magnetic resonance imaging. All participants completed the 2-minute step test (2MST), a brief measure of physical fitness. We examined the associations between cognitive performance, physical fitness, and three indices of global brain integrity: Total cortical gray matter volume, total white matter volume, and whole brain cortical thickness.
Regression analyses adjusting for demographic characteristics, medical variables (e.g., left ventricular ejection fraction), and intracranial volume revealed reduced performance on the 2MST was associated with decreased gray matter volume and thinner cortex (p < .05). Follow up analyses showed that reduced gray matter volume and decreased cortical thickness were associated with poorer 3MS scores (p < .05).
Poor physical fitness is common in HF and associated with reduced structural brain integrity. Prospective studies are needed to elucidate underlying mechanisms for the influence of physical fitness on brain health in HF.
PMCID: PMC3625509  PMID: 23528350
Brain; cognitive function; heart failure; neuroimaging; physical fitness
13.  An fMRI Study of Nicotine-Deprived Smokers' Reactivity to Smoking Cues during Novel/Exciting Activity 
PLoS ONE  2014;9(4):e94598.
Engaging in novel/exciting (“self-expanding”) activities activates the mesolimbic dopamine pathway, a brain reward pathway also associated with the rewarding effects of nicotine. This suggests that self-expanding activities can potentially substitute for the reward from nicotine. We tested this model among nicotine-deprived smokers who, during fMRI scanning, played a series of two-player cooperative games with a relationship partner. Games were randomized in a 2 (self-expanding vs. not) x 2 (cigarette cue present vs. absent) design. Self-expansion conditions yielded significantly greater activation in a reward region (caudate) than did non-self-expansion conditions. Moreover, when exposed to smoking cues during the self-expanding versus the non-self-expanding cooperative games, smokers showed less activation in a cigarette cue-reactivity region, a priori defined [temporo-parietal junction (TPJ)] from a recent meta-analysis of cue-reactivity. In smoking cue conditions, increases in excitement associated with the self-expanding condition (versus the non-self-expanding condition) were also negatively correlated with TPJ activation. These results support the idea that a self-expanding activity promoting reward activation attenuates cigarette cue-reactivity among nicotine-deprived smokers. Future research could focus on the parameters of self-expanding activities that produce this effect, as well as test the utility of self-expansion in clinical interventions for smoking cessation.
PMCID: PMC3984235  PMID: 24727905
14.  The Adverse Impact of Type 2 Diabetes on Brain Volume in Heart Failure 
Heart failure (HF) is associated with structural brain abnormalities, including atrophy in multiple brain regions. Type 2 diabetes mellitus (T2DM) is a prevalent comorbid condition in HF and is associated with abnormalities on neuroimaging in other medical and elderly samples. The current study examined whether comorbid T2DM exacerbates brain atrophy in older adults with HF.
Seventy-five older adults with HF underwent echocardiogram, and completed a brief cognitive test battery. Participants then underwent brain magnetic resonance imaging (MRI) to quantify total brain volumes, cortical lobar volumes, and white matter hyperintensities (WMH).
Approximately 30% of HF patients had a comorbid T2DM diagnosis. A series of MANCOVA analyses adjusting for medical and demographic characteristics and intracranial volume showed that HF patients with T2DM had smaller total brain, gray matter, and subcortical gray matter volume than those without such history. No between group differences emerged for WMH. Persons with T2DM also had smaller cortical lobar volumes, including in frontal, temporal, and parietal lobes. Follow-up analyses revealed smaller total and cortical lobar brain volumes and WMH were associated with poorer performance on measures of global cognitive status, attention, executive functions, and memory.
T2DM is associated with smaller total and cortical lobar brain volumes in patients with HF and these structural brain indices were associated with cognitive test performance. Prospective studies that directly monitor glucose levels are needed to confirm our findings and clarify the mechanisms by which T2DM adversely impacts brain atrophy in this population.
PMCID: PMC3633205  PMID: 23419083
Brain; cognitive function; heart failure; type 2 diabetes; neuroimaging
15.  The Independent Association of Hypertension with Cognitive Function Among Older Adults with Heart Failure 
Journal of the neurological sciences  2012;323(1-2):216-220.
Hypertension is the most common comorbidity among heart failure (HF) patients and has been independently linked with cognitive impairment. Cognitive impairment is prevalent among HF patients, though the extent to which hypertension contributes to cognitive function in this population is unclear.
116 HF patients (31.0% women, 67.68 ± 11.16 years) completed neuropsychological testing and impedance cardiography. History of physician diagnosed hypertension, along with other medical characteristics, was ascertained through a review of participants’ medical charts.
69.8% of the HF patients had a diagnostic history of hypertension. After adjustment for demographic and medical characteristics (i.e., cardiac index, medication status, and resting blood pressure), hypertension was independently associated with attention/executive function/psychomotor speed (ΔF(1,103) = 10.85, ΔR2 = .07, p < .01) and motor functioning (ΔF(1,103) = 4.46, ΔR2 = .04, p < .05). HF patients with a diagnosed history of hypertension performed worse in these domains than those without such history.
The current findings indicate that diagnostic history of hypertension is an important contributor to cognitive impairment in HF. Hypertension frequently precedes HF and future studies should examine whether sustained hypertension compromises cerebral autoregulatory mechanisms to produce brain damage and exacerbate cognitive impairment in this population.
PMCID: PMC3483380  PMID: 23026535
Cognitive function; cardiac index; heart failure; hypertension; blood pressure
16.  Cognitive Function and Treatment Adherence in Older Adults with Heart Failure 
Psychosomatic medicine  2012;74(9):965-973.
Treatment recommendation and guidelines for patients with heart failure (HF) can be complex, and past work has shown HF patients to demonstrate low rates of adherence to recommended health behaviors. While previous work has identified several medical, demographic, and psychosocial predictors of HF persons’ capacity to adhere to treatment recommendations, little is known about the contribution of cognitive impairment to reported treatment adherence in this population.
149 persons with HF (68.08 years; SD = 10.74) completed a brief fitness assessment and neuropsychological testing. Treatment adherence was assessed using the Heart Failure Compliance Questionnaire, a brief measure that asks participants to report their adherence to a variety of recommended health behaviors (i.e., medication management, diet, exercise, among others).
16.1% of participants reported poor overall adherence, with particularly high rates of non-adherence to dietary and exercise recommendations. Hierarchical regression analyses adjusting for possible confounds revealed reduced performance on attention (β = .26, p = .01), executive function (β = .18, p = .04), and language (β = .22, p = .01) were associated with poorer overall adherence. Follow-up analyses showed these cognitive domains were associated with behaviors such as keeping doctor appointments, medication management, and dietary recommendations (p < .05 for all).
The current findings demonstrate that cognitive function is an independent contributor to adherence in older adults with HF. Prospective studies that objectively measure treatment adherence are needed to clarify these findings and identify possible strategies to improve outcomes in this population.
PMCID: PMC3498588  PMID: 23115344
attention; executive function; heart failure; treatment adherence; cognitive impairment
17.  Depression is Associated with Reduced Physical Activity in Persons with Heart Failure 
Reduced physical activity is common in persons with heart failure (HF). However, studies of correlates and modifiers of physical activity in this population rarely employ objective measures. Motivational and mood related factors that may exacerbate inactivity in HF patients are also rarely investigated. In this study, we examined the relationship between physical activity as assessed by accelerometry, and depression in older adults with HF.
At baseline, older adults with HF (N = 96; 69.81 ± 8.79) wore an accelerometer for seven days, and completed a brief fitness assessment, neuropsychological testing, and psychosocial measures including the Beck Depression Inventory-II (BDI-II). Medical and demographic history was obtained through record review and self-report.
Accelerometer measures showed that HF patients averaged 587 minutes of sedentary time and just 0.31 minutes of vigorous activity per day. Lower daily step count was associated with poorer quality of life and reduced cognitive function. A multiple linear regression adjusting for important demographic and medical variables found that greater number of depressive symptoms on the BDI-II independently predicted lower physical activity levels.
Consistent with past work, the current study found that low physical activity is common in older adults with HF. Depression is an independent predictor of physical activity in older adults with HF and reduced physical activity is associated with numerous adverse psychosocial outcomes. Future studies need to determine whether treatment of depression can boost physical activity and thus improve health outcomes in this population.
PMCID: PMC3610332  PMID: 22924448
Physical Activity; heart failure; depression; psychosocial outcomes; step count
18.  The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease 
Brain and Behavior  2013;3(6):626-636.
It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL).
Materials and methods
52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness.
Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness.
Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults.
Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion.
PMCID: PMC3868168  PMID: 24363966
Arterial spin labeling; cardiovascular disease; cerebral blood flow; cerebrovascular disease; cognitive function; magnetic resonance imaging; neuroimaging
19.  Reduced cerebral blood flow and white matter hyperintensities predict poor sleep in heart failure 
Poor sleep is common in heart failure (HF), though mechanisms of sleep difficulties are not well understood. Adverse brain changes among regions important for sleep have been demonstrated in patients with HF. Cerebral hypoperfusion, a correlate of sleep quality, is also prevalent in HF and a likely contributor to white matter hyperintensities (WMH). However, no study to date has examined the effects of cerebral blood flow, WMH, and brain volume on sleep quality in HF.
Fifty-three HF patients completed the Pittsburgh Sleep Quality Index and underwent brain magnetic resonance imaging to quantify brain and WMH volume. Transcranial Doppler ultrasonography assessed cerebral blood flow velocity of the middle cerebral artery (CBF-V of the MCA).
75.5% of HF patients reported impaired sleep. Regression analyses adjusting for medical and demographic factors showed decreased CBF-V of the MCA and greater WMH volume were associated with poor sleep quality. No such pattern emerged on total brain or regional volume indices.
Decreased cerebral perfusion and greater WMH may contribute to sleep difficulties in HF. Future studies are needed to confirm these findings and clarify the effects of cerebral blood flow and WMH on sleep in healthy and patient samples.
PMCID: PMC3816301  PMID: 24171759
Sleep quality; Heart failure; MRI; Brain perfusion; White matter hyperintensity
20.  Reduced memory in fat mass and obesity-associated allele carriers among older adults with cardiovascular disease 
Much attention has been paid to the prevalence and predisposition of the fat mass and obesity-associated (FTO) gene to obesity, although only a few studies have characterized the extent to which this affects cognitive function. This study examined differences between risk allele carriers (i.e. FTO-AC/AA) and non-carriers (i.e. FTO-CC) on indices of attention/executive function/psychomotor speed, memory, language, and visual-spatial ability in a sample of older patients with cardiovascular disease.
We recruited 120 older adults from an outpatient cardiology clinic who underwent blood draw and completed neuropsychological testing. Participants were classified into two groups: one for those who were homozygous for the non-risk-conferring allele (i.e. FTO-CC) (n = 49) and the other for those who had at least one copy of the obesity risk-conferring A allele (i.e. FTO-AC/AA) (n = 71).
Mancova analyses adjusting for age and years of education revealed the FTO-AC/AA group performed significantly worse on indices of memory (λ = 0.94, F(2, 115) = 3.58, P = 0.03, partial η2 = 0.06). Follow-up tests revealed a significant effect for the FTO-AC/AA group, relative to the non-carrier group, on encoding (i.e. California Verbal Learning Test Total Learning) and California Verbal Learning Test long-delay free recall (P < 0.05). No such differences between FTO carriers and non-carriers emerged on tests of attention/executive function/psychomotor speed, language, or visual-spatial ability (P > 0.05 for all).
These findings suggest that the FTO risk allele is associated with reduced memory performance, particularly on aspects of memory encoding and delayed recall. To elucidate underlying mechanisms, these findings will need to be replicated in larger samples that utilize neuroimaging.
PMCID: PMC3806216  PMID: 23551410
cardiovascular disease; cognitive function; FTO risk allele; memory; obesity
21.  Effects of HIV and Early Life Stress on Amygdala Morphometry and Neurocognitive Function 
Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals.
PMCID: PMC3575741  PMID: 22621973
HIV; Stress; Amygdala; Neuroimaging; Cognition
22.  Cognitive Profiles in Heart Failure: A Cluster Analytic Approach 
Cognitive impairment is common among individuals with heart failure (HF), but the exact nature of these impairments remains unclear. The current study examined 140 older adults with heart failure and sought to determine whether there are distinct cognitive profiles using a cluster analytic approach. Results indicated three unique profiles comprising of individuals who were cognitively intact, memory impaired, and globally impaired. Clusters differed on several important demographic and clinical characteristics. These findings suggest cognitive impairment in persons with HF is more heterogeneous than commonly believed and have important implications for treatment recommendations.
PMCID: PMC3341622  PMID: 22375800
heart failure; cognitive function; cognitive profiles; older adults; cluster analysis
23.  The neuroeconomics of nicotine dependence: A preliminary study of delay discounting of monetary and cigarette rewards in smokers using fMRI 
Psychiatry research  2012;202(1):20-29.
Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence.
PMCID: PMC3530421  PMID: 22633679
Nicotine dependence; smoking; tobacco; behavioral economics; neuroeconomics; delay discounting; impulsivity
24.  Cortical thickness of the cognitive control network in obesity and successful weight loss maintenance: A preliminary MRI study 
Psychiatry Research  2012;202(1):77-79.
Cortical thickness of the cognitive control network was contrasted between obese (OB), successful weight loss maintainers (SWLM), and lean individuals. OB had significant thinning, most notably in the anterior cingulate and posterior parietal cortices. SWLM exhibited trends towards thicker cortex than OB, which may be important in future studies.
PMCID: PMC3380138  PMID: 22595506
obese; magnetic resonance imaging; Freesurfer
25.  A fMRI Study of Verbal Working Memory, Cardiac Output, and Ejection Fraction in Elderly Patients with Cardiovascular Disease 
Brain imaging and behavior  2009;3(4):350-357.
Cardiovascular disease (CVD) is associated with cognitive deficits even in the absence of stroke. We examined the relationship between cardiac performance, as measured by cardiac output (CO) and ejection fraction (EF), and brain activity during a verbal working memory (VWM) task in elderly CVD patients who tend to be at increased risk for vascular cognitive impairments. Seventeen patients were recruited from a cohort participating in an ongoing prospective study examining the effects of CVD on cognitive function in the elderly. Participants were diagnosed with CVD (age 68±8) and completed a 2-back VWM task in a 1.5T fMRI paradigm. CO and EF were calculated from echocardiogram measures. Task-related activation was averaged in a priori regions of interest. The relationship between CO, EF, and 2-back-related activity was modeled using partial correlations (two-tailed p<.05) controlling for age and 2-back accuracy. All participants were globally cognitively intact as indicated by Mini-Mental Status Exam and Dementia Rating Scale scores. Mean accuracy on the 2-back was 78±9% while reaction time averaged 1,027±192 ms. Mean CO and EF values showed a large range (CO: 3.55 to 6.31; EF: 0.36 to 0.76) but average values were within the normal range. After controlling for age and 2-back accuracy, lower EF was related to decrease in left insula activity (r=0.61, p=0.03). There were trends for EF to be related to accuracy (r=0.47, p=0.09) and reaction time (r=−0.48, p=0.09). CO was also related to insula activity (r=0.60, p=0.04) and activity in the supplementary motor area activity (r=0.66, p=0.01). Cardiac performance was related to decreased efficiency in task related brain areas and tended to be related to performance on a VWM task in elderly patients with CVD. Results have implications for a line of investigation indicating that cardiac and systemic vascular indices could be used as proxy measures to examine mechanisms of cerebrovascular dysfunction in the elderly.
PMCID: PMC3514458  PMID: 23227137
Functional magnetic resonance imaging; FMRI; Functional neuroimaging; Verbal working memory; Cardiovascular disease; Heart disease; Ejection fraction; Cardiac output

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