Does Functional Variation in Cognitive Control Systems of the Brain Link Reappraisal to the Metabolic Syndrome

Negative emotionality is associated with an increased risk for developing the metabolic syndrome (MetS). Presumably, negative emotionality partly confers such risk via alterations in peripheral autonomic and neuroendocrine effector pathways that promote metabolic pathophysiology. Conversely, protection against risk for the MetS may be conferred by an individual’s tendency to use cognitive strategies to regulate negative emotions. However, the brain systems by which cognitive emotion regulation relates to the MetS are unknown. Accordingly, we examined whether prefrontal and cingulate brain systems that jointly support cognitive emotion regulation and control peripheral physiological responses to negative emotional states represent a pathway linking emotion regulation to the MetS. Middle-aged adults (N=139; 74 men; mean age, 40.39 ± 6.2 years) underwent an fMRI scan while performing a Stroop color-word task that requires cognitive control, evokes a negative emotional state, and engages prefrontal and cingulate brain areas. Individual differences in self-reported tendencies to use cognitive reappraisal as an emotion regulation strategy were assessed by the Emotion Regulation Questionnaire (ERQ). The presence of the MetS was determined using the criteria of the National Cholesterol Education Program, Adult Treatment Panel III. After adjusting for age and sex, frequent cognitive reappraisal usage was associated with reduced likelihood of having the MetS and with meeting fewer MetS criteria. Moreover, fMRI psychophysiological interaction analyses revealed that increasing task-evoked functional connectivity between the dorsal anterior cingulate (dACC) and dorsolateral prefrontal cortex (DLPFC) was associated with frequent cognitive reappraisal usage, reduced presence of the MetS, and meeting less MetS criteria, net the influence of age and sex. In an exploratory mediation analysis, this positive dACC-DLPFC connectivity mediated the association between cognitive reappraisal and the MetS. Individuals who frequently use cognitive reappraisal may be at lesser MetS risk in part via an enhanced capacity to recruit prefrontal cognitive control systems during negative affective states

Cerebral blood flow links insulin resistance and baroreflex sensitivity

Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old) who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05). Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01). Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes. © 2013 Ryan et al

Brain systems for baroreflex suppression during stress in humans

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

Basal ganglia morphology links the metabolic syndrome and depressive symptoms

AbstractThe metabolic syndrome (MetS) is a clustering of cardiovascular and cerebrovascular risk factors that are often comorbid with depressive symptoms. Individual components of the MetS also covary with the morphology of basal ganglia regions that are altered by depression. However, it remains unknown whether the covariation between the MetS and depressive symptomatology can be accounted for in part by morphological changes in the basal ganglia. Accordingly, we tested the hypothesis that increased depressive symptoms among individuals with the MetS might be statistically mediated by reduced gray matter volume in basal ganglia regions. The presence of the MetS was determined in 147 middle-aged adults using the criteria of the National Cholesterol Education Program, Adult Treatment Panel III. Basal ganglia volumes were determined on an a priori basis by automated segmentation of high-resolution magnetic resonance images. Depressive symptoms were assessed using the Patient Health Questionnaire. Even after controlling for demographic and other confounding factors, having the MetS and meeting more MetS criteria covaried with reduced globus pallidus volume. Meeting more MetS criteria and reduced pallidal volume were also related to depressive symptoms. Moreover, the MetS-depression association was statistically mediated by pallidal volume. In summary, reduced globus pallidus volume is a neural correlate of the MetS that may partly account for its association with depressive symptoms

Cerebral blood flow links insulin resistance and baroreflex sensitivity.

<p>Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old) who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05). Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01). Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes.</p

Regions that statistically mediated the relationship between insulin resistance (IR) and baroreflex sensitivity (BRS).

<p>Results presented are ‘path a*b’ regression coefficient output from the BRAVO mediation toolbox. Regions displayed statistically mediated the relationship between IR and BRS after covarying for resting systolic blood pressure, age, sex, waist circumference and global cerebral bloodflow. To correct for multiple comparisons, a cluster threshold was utilized (<i>p</i>-uncorrected = .005, k = 109) to maintain a whole brain threshold of <i>p</i> < .05.</p