RESUMEN
Residing in communities of socioeconomic disadvantage confers risk for chronic diseases and cognitive aging, as well as risk for biological factors that negatively affect brain morphology. The present study tested whether community disadvantage negatively associates with brain morphology via 2 biological factors encompassing cardiometabolic disease risk and neuroendocrine function. Participants were 448 midlife adults aged 30-54 years (236 women) who underwent structural neuroimaging to assess cortical and subcortical brain tissue morphology. Community disadvantage was indexed by US Census data geocoded to participants' residential addresses. Cardiometabolic risk was indexed by measurements of adiposity, blood pressure, glucose, insulin, and lipids. Neuroendocrine function was indexed from salivary cortisol measurements taken over 3 days, from which we computed the cortisol awakening response, area-under-the-curve, and diurnal cortisol decline. Community disadvantage was associated with reduced cortical tissue volume, cortical surface area, and cortical thickness, but not subcortical morphology. Moreover, increased cardiometabolic risk and a flatter (dysregulated) diurnal cortisol decline mediated the associations of community disadvantage and cortical gray matter volume. These effects were independent of age, sex, and individual-level socioeconomic position. The adverse risks of residing in a disadvantaged community may extend to the cerebral cortex via cardiometabolic and neuroendocrine pathways.
Asunto(s)
Sistema Cardiovascular/fisiopatología , Corteza Cerebral/fisiopatología , Sistemas Neurosecretores/fisiopatología , Factores Socioeconómicos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease.
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Encéfalo/diagnóstico por imagen , Inflamación/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Adulto , Encéfalo/fisiopatología , Mapeo Encefálico , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Inflamación/sangre , Inflamación/fisiopatología , Interleucina-6/sangre , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiopatologíaRESUMEN
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
Asunto(s)
Adultos Sobrevivientes del Maltrato a los Niños , Giro del Cíngulo/diagnóstico por imagen , Veteranos , Sustancia Blanca/diagnóstico por imagen , Adolescente , Adulto , Imagen de Difusión Tensora , Humanos , Masculino , Red Nerviosa/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults. METHODS: Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30-54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer. RESULTS: Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition. CONCLUSIONS: Inflammation and adiposity might relate to cognitive decline via influences on brain morphology.
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Encéfalo/patología , Proteína C-Reactiva/metabolismo , Cognición/fisiología , Inflamación/patología , Interleucina-6/sangre , Adulto , Función Ejecutiva , Femenino , Humanos , Inflamación/sangre , Inflamación/psicología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Tamaño de los Órganos/fisiologíaRESUMEN
OBJECTIVES: Generalized anxiety disorder (GAD) is one of the most prevalent mental disorders in the elderly, but its functional neuroanatomy is not well understood. Given the role of emotion dysregulation in GAD, we sought to describe the neural bases of emotion regulation in late-life GAD by analyzing the functional connectivity (FC) in the Salience Network and the Executive Control Network during worry induction and worry reappraisal. METHODS: The study included 28 elderly GAD and 31 non-anxious comparison participants. Twelve elderly GAD completed a 12-week pharmacotherapy trial. We used an in-scanner worry script that alternates blocks of worry induction and reappraisal. We assessed network FC, using the following seeds: anterior insula (AI), dorsolateral prefrontal cortex (dlPFC), the bed nucleus of stria terminalis (BNST), and the paraventricular nucleus (PVN). RESULTS: GAD participants exhibited greater FC during worry induction between the left AI and the right orbitofrontal cortex, and between the BNST and the subgenual cingulate. During worry reappraisal, the non-anxious participants had greater FC between the left dlPFC and the medial PFC, as well as between the left AI and the medial PFC, and elderly GAD patients had greater FC between the PVN and the amygdala. Following 12 weeks of pharmacotherapy, GAD participants had greater connectivity between the dlPFC and several prefrontal regions during worry reappraisal. CONCLUSION: FC during worry induction and reappraisal points toward abnormalities in both worry generation and worry reappraisal. Following successful pharmacologic treatment, we observed greater connectivity in the prefrontal nodes of the Executive Control Network during reappraisal of worry.
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Envejecimiento/fisiología , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/psicología , Emociones/efectos de los fármacos , Anciano , Envejecimiento/efectos de los fármacos , Envejecimiento/psicología , Trastornos de Ansiedad/fisiopatología , Mapeo Encefálico , Estudios de Casos y Controles , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiopatología , Citalopram/farmacología , Citalopram/uso terapéutico , Emociones/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/fisiopatología , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Núcleos Septales/efectos de los fármacos , Núcleos Septales/fisiopatología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
OBJECTIVES: Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders, but its neural basis is relatively understudied. This study aims to characterize the functional connectivity in the default mode network (DMN) in GAD across the lifespan. DESIGN AND SETTINGS: Functional and structural magnetic resonance imaging data were collected with subjects at rest. We analyzed the resting state functional connectivity patterns in the DMN for 27 GAD participants and 39 non-anxious comparison participants. Using a two-way analysis of variance, we explored the interaction between age and GAD status on functional connectivity. In GAD participants, we analyzed the correlation of functional connectivity indices with the duration of illness and worry severity. RESULTS: The age-by-anxiety interaction showed a greater anxiety effect on the functional connectivity between the posterior cingulate seed and the medial prefrontal cortex for the older group relative to the younger participants. Longer duration of illness was positively correlated with greater functional connectivity between the posterior cingulate cortex and the insula. Worry severity was inversely correlated with the functional connectivity between the posterior cingulate cortex seed and the medial prefrontal cortex. CONCLUSION: The presence of GAD, longer duration of illness, and more severe worry exacerbate the effects of age on the functional connectivity in the DMN. These results support the need for tailored research and interventions in late-life anxiety.
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Factores de Edad , Trastornos de Ansiedad/fisiopatología , Corteza Prefrontal/fisiología , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
Socioeconomic disadvantage confers risk for aspects of ill health that may be mediated by systemic inflammatory influences on the integrity of distributed brain networks. Following this hypothesis, we tested whether socioeconomic disadvantage related to the structural integrity of white matter tracts connecting brain regions of distributed networks, and whether such a relationship would be mediated by anthropometric, behavioral, and molecular risk factors associated with systemic inflammation. Otherwise healthy adults (N= 155, aged 30-50 years, 78 men) completed protocols assessing multilevel indicators of socioeconomic position (SEP), anthropometric and behavioral measures of adiposity and cigarette smoking, circulating levels of C-reactive protein (CRP), and white matter integrity by diffusion tensor imaging. Mediation modeling was used to test associations between SEP indicators and measures of white matter tract integrity, as well as indirect mediating paths. Measures of tract integrity followed a socioeconomic gradient: individuals completing more schooling, earning higher incomes, and residing in advantaged neighborhoods exhibited increases in white matter fractional anisotropy and decreases in radial diffusivity, relative to disadvantaged individuals. Moreover, analysis of indirect paths showed that adiposity, cigarette smoking, and CRP partially mediated these effects. Socioeconomic inequalities may relate to diverse health disparities via inflammatory pathways impacting the structural integrity of brain networks.
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Corteza Cerebral/patología , Inflamación , Adulto , Proteína C-Reactiva/análisis , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SocioeconómicosRESUMEN
Being overweight or obese is associated with reduced white matter integrity throughout the brain. It is not yet clear which physiological systems mediate the association between inter-individual variation in adiposity and white matter. We tested whether composite indicators of cardiovascular, lipid, glucose, and inflammatory factors would mediate the adiposity-related variation in white matter microstructure, measured with diffusion tensor imaging on a group of neurologically healthy adults (N=155). A composite factor representing adiposity (comprised of body mass index and waist circumference) was associated with smaller fractional anisotropy and greater radial diffusivity throughout the brain, a pattern previously linked to myelin structure changes in non-human animal models. A similar global negative association was found for factors representing inflammation and, to a lesser extent, glucose regulation. In contrast, factors for blood pressure and dyslipidemia had positive associations with white matter in isolated brain regions. Taken together, these competing influences on the diffusion signal were significant mediators linking adiposity to white matter and explained up to fifty-percent of the adiposity-white matter variance. These results provide the first evidence for contrasting physiological pathways, a globally distributed immunity-linked negative component and a more localized vascular-linked positive component, that associate adiposity to individual differences in the microstructure of white matter tracts in otherwise healthy adults.
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Grasa Abdominal/fisiología , Adiposidad/fisiología , Índice de Masa Corporal , Encéfalo/fisiología , Encéfalo/ultraestructura , Fibras Nerviosas Mielínicas/ultraestructura , Circunferencia de la Cintura/fisiología , Adulto , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadística como AsuntoRESUMEN
The arterial baroreflex is a key mechanism for the homeostatic control of blood pressure (BP). In animals and humans, psychological stressors suppress the capacity of the arterial baroreflex to control short-term fluctuations in BP, reflected by reduced baroreflex sensitivity (BRS). While animal studies have characterized the brain systems that link stressor processing to BRS suppression, comparable human studies are lacking. Here, we measured beat-to-beat BP and heart rate (HR) in 97 adults who performed a multisource interference task that evoked changes in spontaneous BRS, which were quantified by a validated sequence method. The same 97 participants also performed the task during functional magnetic resonance imaging (fMRI) of brain activity. Across participants, task performance (i) increased BP and HR and (ii) reduced BRS. Analyses of fMRI data further demonstrated that a greater task-evoked reduction in BRS covaried with greater activity in brain systems important for central autonomic and cardiovascular control, particularly the cingulate cortex, insula, amygdala, and midbrain periaqueductal gray (PAG). Moreover, task performance increased the functional connectivity of a discrete area of the anterior insula with both the cingulate cortex and amygdala. In parallel, this same insula area showed increased task-evoked functional connectivity with midbrain PAG and pons. These novel findings provide human evidence for the brain systems presumptively involved in suppressing baroreflex functionality, with relevance for understanding the neurobiological mechanisms of stressor-related cardiovascular reactivity and associated risk for essential hypertension and atherosclerotic heart disease.
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Barorreflejo/fisiología , Encéfalo/fisiología , Inhibición Neural/fisiología , Estrés Psicológico/fisiopatología , Adulto , Presión Sanguínea/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Desempeño Psicomotor/fisiología , Estrés Psicológico/psicologíaRESUMEN
OBJECTIVE: Insulin resistance (IR) confers risk for Type 2 diabetes and is associated with depressed mood. Neurons within the ventral striatum (VS) are sensitive to insulin levels and show altered function in the context of both IR and depression. Hence, VS may represent a critical component of a neural circuitry linking IR to depressed mood. METHODS: Ninety adults (aged 30-50 years) free from major psychiatric illnesses and diabetes participated. Fasting blood was sampled, and participants completed a set of questionnaires (including the Beck Depression Inventory-II). Participants also underwent resting-state functional magnetic resonance imaging of the brain. Seed-based connectivity analyses, centered on VS, were conducted to examine how resting-state interregional connectivity patterns covaried with IR and depressed mood. RESULTS: Higher levels of IR covaried with increased connective strength between the left VS and two regions: the insula and the anterior midcingulate cortex (aMCC). Moreover, aMCC-VS connectivity predicted depressed mood (b = 0.93, standard error = 0.36, F(change)(1,81) = 6.54, p = .01). Finally, aMCC-VS connectivity was shown by Monte Carlo analysis to mediate the relationship between IR and depressed mood (a*b indirect effect = 0.16, confidence interval = 0.005-0.39, p = .03). CONCLUSIONS: IR relates to changes in the functional connectivity between VS and aMCC. These changes in interregional communication partly account for the coupling of IR to depressed mood in otherwise healthy adults. These findings are relevant for understanding bidirectional associations between diabetes risk and depressed mood.
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Ganglios Basales/fisiopatología , Depresión/fisiopatología , Giro del Cíngulo/fisiopatología , Resistencia a la Insulina/fisiología , Adulto , Ganglios Basales/metabolismo , Mapeo Encefálico/métodos , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Depresión/metabolismo , Femenino , Giro del Cíngulo/metabolismo , Homeostasis/fisiología , Humanos , Insulina/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Método de Montecarlo , Red Nerviosa/fisiopatología , Escalas de Valoración Psiquiátrica , Análisis de RegresiónRESUMEN
Socioeconomic disadvantage experienced in early development predicts ill health in adulthood. However, the neurobiological pathways linking early disadvantage to adult health remain unclear. Lower parental education-a presumptive indicator of early socioeconomic disadvantage-predicts health-impairing adult behaviors, including tobacco and alcohol dependencies. These behaviors depend, in part, on the functionality of corticostriatal brain systems that 1) show developmental plasticity and early vulnerability, 2) process reward-related information, and 3) regulate impulsive decisions and actions. Hence, corticostriatal functionality in adulthood may covary directly with indicators of early socioeconomic disadvantage, particularly lower parental education. Here, we tested the covariation between parental education and corticostriatal activation and connectivity in 76 adults without confounding clinical syndromes. Corticostriatal activation and connectivity were assessed during the processing of stimuli signaling monetary gains (positive feedback [PF]) and losses (negative feedback). After accounting for participants' own education and other explanatory factors, lower parental education predicted reduced activation in anterior cingulate and dorsomedial prefrontal cortices during PF, along with reduced connectivity between these cortices and orbitofrontal and striatal areas implicated in reward processing and impulse regulation. In speculation, adult alterations in corticostriatal functionality may represent facets of a neurobiological endophenotype linked to socioeconomic conditions of early development.
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Corteza Cerebral/fisiología , Escolaridad , Vías Nerviosas/fisiología , Padres , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Factores SocioeconómicosRESUMEN
Exaggerated cardiovascular reactivity to stress is a risk factor for cardiovascular disease. Further, individual differences in stressor-evoked cardiovascular reactivity covary with the functionality of corticolimbic brain systems, particularly areas of the cingulate cortex. What remains unclear, however, is how individual differences in personality traits interact with cingulate functionality in the prediction of stressor-evoked cardiovascular reactivity. Accordingly, we tested the associations between (i) a particular personality trait, Agreeableness, which is associated with emotional reactions to conflict, (ii) resting state functional connectivity within the cingulate cortex, and (iii) stressor-evoked blood pressure (BP) reactivity. Participants (N=39, 19 men, aged 20-37 years) completed a resting functional connectivity MRI protocol, followed by two standardized stressor tasks that engaged conflict processing and evoked BP reactivity. Agreeableness covaried positively with BP reactivity across individuals. Moreover, connectivity analyses demonstrated that a more positive functional connectivity between the posterior cingulate (BA31) and the perigenual anterior cingulate (BA32) covaried positively with Agreeableness and with BP reactivity. Finally, statistical mediation analyses demonstrated that BA31-BA32 connectivity mediated the covariation between Agreeableness and BP reactivity. Functional connectivity within the cingulate appears to link Agreeableness and a risk factor for cardiovascular disease, stressor-evoked BP reactivity.
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Presión Sanguínea , Giro del Cíngulo/fisiopatología , Red Nerviosa/fisiopatología , Vías Nerviosas/fisiopatología , Descanso , Estrés Psicológico/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
Individuals who exhibit exaggerated blood pressure reactions to psychological stressors are at risk for hypertension, ventricular hypertrophy, and premature atherosclerosis; however, the neural systems mediating exaggerated blood pressure reactivity and associated cardiovascular risk in humans remain poorly defined. Animal models indicate that the amygdala orchestrates stressor-evoked blood pressure reactions via reciprocal signaling with corticolimbic and brainstem cardiovascular-regulatory circuits. Based on these models, we used a multimodal neuroimaging approach to determine whether human individual differences in stressor-evoked blood pressure reactivity vary with amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem areas implicated in stressor processing and cardiovascular regulation. We monitored mean arterial pressure (MAP) and concurrent functional magnetic resonance imaging BOLD signal changes in healthy young individuals while they completed a Stroop color-word stressor task, validated previously in epidemiological studies of cardiovascular risk. Individuals exhibiting greater stressor-evoked MAP reactivity showed (1) greater amygdala activation, (2) lower amygdala gray matter volume, and (3) stronger positive functional connectivity between the amygdala and perigenual anterior cingulate cortex and brainstem pons. Individual differences in amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem circuits may partly underpin cardiovascular disease risk by impacting stressor-evoked blood pressure reactivity.
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Amígdala del Cerebelo/fisiología , Presión Sanguínea/fisiología , Individualidad , Red Nerviosa/fisiología , Estrés Psicológico/fisiopatología , Adolescente , Adulto , Amígdala del Cerebelo/anatomía & histología , Femenino , Humanos , Masculino , Red Nerviosa/anatomía & histología , Tamaño de los Órganos/fisiología , Puente/anatomía & histología , Puente/fisiologíaRESUMEN
An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the 'brain-body' pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala--as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the 'brain-body' pathways that mechanistically link stressful experiences with CHD risk.
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Presión Sanguínea/fisiología , Encéfalo/fisiología , Enfermedad Coronaria/fisiopatología , Estrés Psicológico/fisiopatología , Animales , Sistema Cardiovascular/fisiopatología , Humanos , Factores de RiesgoRESUMEN
OBJECTIVE: To test whether current gray matter volume (GMV) covaried with previously obtained longitudinal measures of weight gain-as assessed by increases in body mass index (BMI)-among otherwise healthy postmenopausal women. Cross-sectional results indicate that reduced GMV may be associated with excess body weight. METHODS: Demographic, biometric, and behavioral measures were obtained from 48 women as part of the Pittsburgh Healthy Women Study, a longitudinal epidemiological investigation initiated between 1983 and 1984. In 2005 and 2006, these women took part in a brain imaging protocol. RESULTS: Premenopausal BMI and a priori chosen confounding variables, including the number of years post menopause, an aggregate measure of perceived life stress spanning a 20-year period, resting blood pressure, total cerebral volume, and severity of white matter hyperintensities (a suspected indicator of aging-related silent cerebrovascular disease), explained approximately 22% of variance in total GMV. An additional 15% of the variance was uniquely explained by the change in BMI between pre- and postmenopausal longitudinal assessments, such that an increase in BMI predicted a greater reduction in GMV. CONCLUSIONS: An increase in BMI during the menopausal transition and beyond is associated with reduced GMV among otherwise healthy women.
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Envejecimiento/patología , Encéfalo/patología , Obesidad/patología , Adiposidad/fisiología , Anciano , Atrofia , Índice de Masa Corporal , Femenino , Humanos , Imagen por Resonancia Magnética , Menopausia/fisiología , Posmenopausia/fisiología , Factores de Riesgo , Aumento de Peso/fisiología , Salud de la MujerRESUMEN
BACKGROUND: Individuals who exhibit large-magnitude blood pressure (BP) reactions to acute psychological stressors are at risk for hypertension and premature death by cardiovascular disease. This study tested whether a multivariate pattern of stressor-evoked brain activity could reliably predict individual differences in BP reactivity, providing novel evidence for a candidate neurophysiological source of stress-related cardiovascular risk. METHODS AND RESULTS: Community-dwelling adults (N=310; 30-51 years; 153 women) underwent functional magnetic resonance imaging with concurrent BP monitoring while completing a standardized battery of stressor tasks. Across individuals, the battery evoked an increase systolic and diastolic BP relative to a nonstressor baseline period (M ∆systolic BP/∆diastolic BP=4.3/1.9 mm Hg [95% confidence interval=3.7-5.0/1.4-2.3 mm Hg]). Using cross-validation and machine learning approaches, including dimensionality reduction and linear shrinkage models, a multivariate pattern of stressor-evoked functional magnetic resonance imaging activity was identified in a training subsample (N=206). This multivariate pattern reliably predicted both systolic BP (r=0.32; P<0.005) and diastolic BP (r=0.25; P<0.01) reactivity in an independent subsample used for testing and replication (N=104). Brain areas encompassed by the pattern that were strongly predictive included those implicated in psychological stressor processing and cardiovascular responding through autonomic pathways, including the medial prefrontal cortex, anterior cingulate cortex, and insula. CONCLUSIONS: A novel multivariate pattern of stressor-evoked brain activity may comprise a phenotype that partly accounts for individual differences in BP reactivity, a stress-related cardiovascular risk factor.
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Presión Sanguínea , Encéfalo/fisiopatología , Sistema Cardiovascular/fisiopatología , Estrés Psicológico/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Análisis Discriminante , Femenino , Humanos , Modelos Lineales , Aprendizaje Automático , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Fenotipo , Análisis de Componente Principal , Factores de Riesgo , Estrés Psicológico/diagnóstico por imagen , Estrés Psicológico/psicologíaRESUMEN
Late-life Generalized Anxiety Disorder (GAD) is relatively understudied and the underlying structural and functional neuroanatomy has received little attention. In this study, we compare the brain structural characteristics in white and gray matter in 31 non-anxious older adults and 28 late-life GAD participants. Gray matter indices (cortical thickness and volume) were measured using FreeSurfer parcellation and segmentation, and mean diffusivity was obtained through Diffusion Tensor Imaging (DTI). We assessed both macroscopic white matter changes [using white matter hyperintensity (WMH) burden] and microscopic white matter integrity [using fractional anisotropy (FA)]. No differences in macro- or microscopic white matter integrity were found between GAD and non-anxious controls (HC). GAD participants had lower cortical thickness in the orbitofrontal cortex (OFC), inferior frontal gyrus, and pregenual anterior cingulate cortex (ACC). Higher worry severity was associated with gray matter changes in OFC, ACC and the putamen. The results did not survive the multiple comparison correction, but the effect sizes indicate a moderate effect. The study suggests that late-life GAD is associated with gray matter changes in areas involved in emotion regulation, more so than with white matter changes. We conclude that anxiety-related chronic hypercortisolemia may have a dissociative effect on gray and white matter integrity.
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Trastornos de Ansiedad/patología , Encéfalo/patología , Sustancia Gris/patología , Sustancia Blanca/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Anisotropía , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/psicología , Encéfalo/diagnóstico por imagen , Síndrome de Cushing/etiología , Síndrome de Cushing/patología , Síndrome de Cushing/psicología , Imagen de Difusión Tensora/métodos , Emociones , Femenino , Sustancia Gris/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/patología , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Índice de Severidad de la Enfermedad , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: High blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure (BP) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow (rCBF) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge. METHODS AND RESULTS: Healthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized ß>0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized ß>0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance. CONCLUSIONS: Relationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention.
Asunto(s)
Circulación Cerebrovascular/fisiología , Cerebro/diagnóstico por imagen , Cognición/fisiología , Prehipertensión/fisiopatología , Adulto , Presión Sanguínea , Cerebro/irrigación sanguínea , Función Ejecutiva , Femenino , Neuroimagen Funcional , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria , Memoria a Corto Plazo , Persona de Mediana Edad , Pruebas Neuropsicológicas , Marcadores de Spin , Análisis y Desempeño de TareasRESUMEN
Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P=0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P=0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife.
Asunto(s)
Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Trastornos del Conocimiento/etiología , Cognición/fisiología , Hipertensión/fisiopatología , Memoria a Corto Plazo/fisiología , Flujo Sanguíneo Regional/fisiología , Adulto , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/fisiopatología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de TiempoRESUMEN
Resting high-frequency heart rate variability (HF-HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF-HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes-open, 5-min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF-HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF-HRV. However, HF-HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF-HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF-HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment.