Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults

Background

In animals, dendritic arborization and levels of brain derived neurotrophic factor are positively associated with intake of the omega-3 fatty acids. Here, we test whether omega-3 fatty acid intake in humans varies with individual differences in gray matter volume, an in vivo, systems-level index of neuronal integrity.

Methods

Fifty-five healthy adults completed two 24 h dietary recall interviews. Intake of long-chain omega-3 fatty acids was categorized by tertiles. Regional gray matter volumes in a putative emotional brain circuitry comprised of the anterior cingulate cortex (ACC), amygdala and hippocampus were calculated using optimized voxel-based morphometry on high-resolution structural magnetic resonance images.

Results

Region of interest analyses revealed positive associations between reported dietary omega-3 intake and gray matter volume in the subgenual ACC, the right hippocampus and the right amygdala, adjusted for total gray matter volume of brain. Unconstrained whole-brain analyses confirmed that higher intake of omega-3 fatty acids was selectively associated with increased greater gray matter volume in these and not other regions.

Conclusions

Higher reported consumption of the long-chain omega-3 fatty acids is associated with greater gray matter volume in nodes of a corticolimbic circuitry supporting emotional arousal and regulation. Such associations may mediate previously observed effects of omega-3 fatty acids on memory, mood and affect regulation.     

Ventromedial prefrontal cortex connectivity during and after psychological stress in women

The ventromedial prefrontal cortex (vmPFC) integrates sensory, affective, memory‐related, and social information from diverse brain systems to coordinate behavioral and peripheral physiological responses according to contextual demands that are appraised as stressful. However, the functionality of the vmPFC during stressful experiences is not fully understood. Among 40 female participants, the present study evaluated (a) functional connectivity of the vmPFC during exposure to and recovery following an acute psychological stressor, (b) associations among vmPFC functional connectivity, heart rate, and subjective reports of stress across individuals, and (c) whether patterns of vmPFC functional connectivity were associated with distributed brain networks. Results showed that psychological stress increased vmPFC functional connectivity with individual brain areas implicated in stressor processing (e.g., insula, amygdala, anterior cingulate cortex) and decreased connectivity with the posterior cingulate cortex and thalamus. There were no statistical differences in vmPFC connectivity to individual brain areas during recovery, as compared with baseline. Spatial similarity analyses revealed stressor‐evoked increased connectivity of the vmPFC with the so‐called dorsal attention, ventral attention, and frontoparietal networks, as well as decreased connectivity with the default mode network. During recovery, vmPFC connectivity increased with the frontoparietal network. Finally, individual differences in heart rate and perceived stress were associated with vmPFC connectivity to the ventral attention, frontoparietal, and default mode networks. Psychological stress appears to alter network‐level functional connectivity of the vmPFC in a manner that further relates to individual differences in stressor‐evoked cardiovascular and affective reactivity.     

The Availability of Social Support Reduces Cardiovascular Reactivity to Acute Psychological Stress

The influence of the availability of social support on cardiovascular reactivity to acute psychological stress was examined. Twenty-eight men and twenty-one women performed a speech task either in a support availability or no support availability condition while measures of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were assessed. Consistent with past research, the speech stressor was associated with significant increases in SBP, DBP, and HR. More important, the availability of social support moderated cardiovascular reactivity to the acute stressor: individuals in the support availability condition were characterized by lower SBP and DBP reactivity to the acute stressor compared to individuals in the no support availability condition. These data suggest that simply having potential access to support is sufficient to foster adaptation to stress in the absence of enacted support.     

Effects of age on volumes of cortex, white matter and subcortical structures

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.     

The plasticity of human maternal brain: longitudinal changes in brain anatomy during the early postpartum period

Animal studies suggest that structural changes occur in the maternal brain during the early postpartum period in regions such as the hypothalamus, amygdala, parietal lobe, and prefrontal cortex and such changes are related to the expression of maternal behaviors. In an attempt to explore this in humans, we conducted a prospective longitudinal study to examine gray matter changes using voxel-based morphometry on high resolution magnetic resonance images of mothers' brains at two time points: 2-4 weeks postpartum and 3-4 months postpartum. Comparing gray matter volumes across these two time points, we found increases in gray matter volume of the prefrontal cortex, parietal lobes, and midbrain areas. Increased gray matter volume in the midbrain including the hypothalamus, substantia nigra, and amygdala was associated with maternal positive perception of her baby. These results suggest that the first months of motherhood in humans are accompanied by structural changes in brain regions implicated in maternal motivation and behaviors.     

Beta‐adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults

Cardiovascular reactivity to stress and β‐adrenergic receptor (β‐AR) function may contribute to the development of hypertension. As Black Americans have an increased risk of hypertension, we evaluated associations between β₁‐AR (Arg389Gly) and β₂‐AR (Arg16Gly, Gln27Glu) gene variants and cardiovascular reactivity in 500 Black youth. Heart rate, preejection period, total peripheral resistance, and blood pressure reactivity were measured during cold and psychological stress. The Arg389Gly polymorphism in the β₁‐AR was associated with preejection period reactivity in males but not in females. The Arg16Gly polymorphism in the β₂‐AR was associated with diastolic blood pressure reactivity only during video game stress. An association between the Gln27Glu polymorphism in the β₂‐AR and vascular reactivity depended on sex. Thus, specific patterns of associations emerged between genetic variations in β‐ARs and cardiovascular reactivity in young Blacks.     

Early parenting predicts hippocampal subregion volume via stress reactivity in childhood

Rodent models indicate that parenting shapes offspring outcomes by programming the hypothalamic–pituitary–adrenal axis response to stress and, ultimately, altering brain structure and function. The present study tested this hypothesis and explored possible timing-dependent associations in a longitudinal sample of children (N = 63). At Time 1 (M = 4.23 ± 0.84 years) and Time 2 (M = 7.20 ± 0.89 years), children completed parent–child interaction tasks and a laboratory stressor after which salivary cortisol samples were collected. At Time 2, children also completed a structural MRI. Analyses revealed timing- and region-dependent associations between early and concurrent parenting and cortisol reactivity and hippocampal subregion volumes. Moreover, greater negative parenting during early childhood predicted greater cortisol reactivity three years later, which, in turn, led to reduced left hippocampal tail volume. Findings suggest that the hippocampus is sensitive to environmental influences during early childhood, a result that parallels findings from rodent models.     

BDNF gene variants and brain morphology in schizophrenia.

The objective was to investigate putative associations between brain-derived neurotrophic factor gene (BDNF) polymorphisms and brain morphology in patients with schizophrenia and healthy control subjects. Four BDNF polymorphisms were genotyped and analyzed versus 39 brain volume measures in 96 patients with schizophrenia or schizoaffective disorder and 104 healthy subjects. In all subjects, quantitative data on segmented gray, white, and cerebrospinal fluid (CSF) tissue class volumes of total brain and major cerebral lobes including ventricular CSF were obtained using magnetic resonance imaging (MRI). In a randomly selected subset of this population (n = 101-122), MR volumes from cerebellar tonsil, hemispheres, and vermis subregions, striatal structures, hippocampus, and corpus callosum were also measured. The BDNF 11757 G/C polymorphism was highly significantly associated with frontal gray matter volume variation in patients alone and in patients and control subjects combined. In patients only, the 270 C/T polymorphism was associated with total caudate volume. Significant associations were demonstrated between the BDNF 11757 G/C and Val66Met polymorphisms and a global haplotype estimate of four BDNF polymorphisms and the posterior superior cerebellar vermis volume in the controls as well as in the combined group, but not in the patients. The 11757 G/C polymorphism was associated with cerebellar hemisphere white and gray matter volumes in the combined group. The BDNF -633 T/A polymorphism was associated with gray matter of the putamen in the controls. Trends for associations between several polymorphisms/haplotype estimates and MRI volumes were found. BDNF gene variation may influence brain morphology. The effects may be different in patients with schizophrenia and healthy subjects.     

Structural correlates of the orbitofrontal cortex and amygdala and personality in female adolescents

The five‐factor model consists of cognitive‐affective‐behavioral trait dimensions (neuroticism, extraversion, openness to experience, agreeableness, conscientiousness) that are central to models of psychopathology. In adults, individual differences in three of the Big Five traits, neuroticism, extraversion, and conscientiousness, have been linked to structural morphology and connectivity of the orbitofrontal cortex (OFC) and the amygdala, two brain regions critically involved in affective and regulatory processing. It is unclear whether these associations manifest in adolescence, a critical neurodevelopmental period during which many forms of psychiatric illness emerge. A total of 223 adolescent girls (ages 14–16 years) completed a multimodal neuroimaging study that utilized T1‐weighted structural MRI (e.g., cortical thickness and volume) and tractography‐based diffusion tensor imaging (64‐direction). Cortical thickness and volume were extracted from the medial orbitofrontal cortex (mOFC) and amygdala and tractography‐based fractional anisotropy was computed in the uncinate fasciculus (UF; the white matter tract connecting the OFC to the temporal lobe). We found that high neuroticism was associated with less mOFC volume (bilateral), and low conscientiousness was associated with higher white matter integrity in the UF, more amygdala volume, and less mOFC thickness (right hemisphere). Extraversion was not observed to share associations with OFC markers. These OFC‐amygdala structural correlations to personality do not match those reported in adult samples. Multimodal neuroimaging techniques can help to clarify the underpinnings of personality development between adolescence and adulthood.     

The effects of nonconcurrent and concurrent relaxation training on cardiovascular reactivity to a psychological stressor

Eight patients in a cardiac rehabilitation program, after exposure to two psychological stressors approximately equivalent with respect to cardiovascular reactivity, were given nonconcurrent progressive muscle relaxation training and retested for reactivity. They were then provided with relaxation training concurrently with one of the stressors and exposed again to the two stressors. No significant effects for nonconcurrent progressive muscle relaxation training were detected. Concurrent training, in contrast, produced reductions in both systolic and diastolic blood pressure. Reductions resulting from training on the target stressor showed little tendency to generalize to the nontarget stressor; the discrimination was particularly well defined for systolic blood pressure. We conclude that muscle relaxation techniques are maximally effective in reducing reactivity to psychological stressors when relaxation training is provided concurrently with the stressor. Our findings further suggest that to inculcate the relaxation response reliably across different situations, specific training to enhance generalization may be needed.     

Perceived stress is associated with smaller hippocampal volume in adolescence

Perceived stress has been associated with decreased hippocampal, amygdala, and prefrontal cortex volume, as well as decreased memory and executive functioning performance in adulthood. Parents' perceived stress has been linked to decreased hippocampal volume in young children. However, no studies have investigated the links between self‐perceived stress and brain structure or function in adolescents. Additionally, findings from previous research with younger or older samples are inconsistent, likely in part due to inconsistencies in participants' age range. In this study, we investigated the associations among self‐perceived stress, family socioeconomic factors (family income, parental education), subcortical (hippocampus, amygdala) volumes, prefrontal cortical thickness and surface area, and memory and executive functioning performance in adolescents. One hundred and forty‐three participants (12–20 years old) were administered a cognitive battery, a questionnaire to assess perceived stress, and a structural MRI scan. Higher levels of perceived stress were associated with decreased adolescent hippocampal volume. This study provides empirical evidence of how experience may shape brain development in adolescence—a period of plasticity during which it may be possible to intervene and prevent negative developmental outcomes.     

The impact of physical proximity and attachment working models on cardiovascular reactivity: Comparing mental activation and romantic partner presence

Close relationships, especially high‐quality romantic relationships, are consistently associated with positive physical health outcomes. Attenuated cardiovascular reactivity is one physiological mechanism implicated in explaining these effects. Drawing on attachment and social baseline theories, this experimental study evaluated two potential affiliative cues as mechanisms through which romantic relationships may attenuate cardiovascular reactivity to a laboratory‐based stressor. Prior to a cold pressor task, 102 participants were randomly assigned to either have their partner physically present, call upon a mental representation of their partner, or think about their day during the stressor. Consistent with our preregistered hypotheses, participants in both the partner present and mental activation conditions had significantly lower blood pressure (BP) reactivity during the cold pressor task compared to control participants for both systolic (d = ?0.54) and diastolic BP (d = ?0.53), but no significant differences emerged for heart rate or heart rate variability. Although participants in the partner present and mental activation conditions had similar BP reactivity to the cold pressor task, those in the partner present condition reported significantly less pain as a result of the task. The difference in BP reactivity by condition was moderated—BP reactivity was greater for people with lower self‐reported relationship satisfaction. The results suggest that accessing the mental representation of a romantic partner and a partner’s presence each buffer against exaggerated acute stress responses to a similar degree.     

Brief Reports: Further evidence for an association between self‐reported health and cardiovascular as well as cortisol reactions to acute psychological stress

In a recent study, the association between cardiovascular reactions to acute psychological stress and self‐reported health was examined. Participants with excellent or good self‐reported health exhibited higher cardiovascular reactivity than those who reported fair or poor health. We investigated this association in a population‐based cohort of whom 725 men and women, aged 55–60 years, participated in a standardized psychological stress test. We measured continuous blood pressure and heart rate as well as cortisol reactivity. Good subjective health was associated with higher cardiovascular and cortisol reactions to psychological stress. Results of the present study confirm those of the previously reported study showing that greater cardiovascular reactivity may not always be associated with negative health outcomes. In addition, the same holds for cortisol reactivity.     

Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls

BACKGROUND: Hippocampal decrease in size in response to posttraumatic stress disorder (PTSD) is still a subject of controversy. The aims of this study were to: (1) confirm previous hippocampus findings in PTSD patients compared to controls, using ethnically similar study groups where alcohol and drug abuse were non-existent; (2) test influence of disease duration as well as depression scores on possible morphological changes; (3) test whether the voxel-based morphometry (VBM) data confirm the group differences seen in the region of interest (ROI) analysis, and (4) test the associations between the cognitive test scores and the morphological changes. METHODS: VBM and ROI-based analysis were applied in 23 patients and 17 healthy controls. Culture-neutral cognitive tests were used. RESULTS: The ROI-based method showed significantly decreased gray matter volumes for global hippocampal volume, as in a separate analysis of left and right sides in the PTSD group. Total volume of the hippocampus was significantly decreased on the left side, as in the global assessment. A multiple regression VBM model showed significant voxel clusters for group affiliation in the right hippocampus, modelling lowering of gray matter associated with the PTSD group. Disease duration was shown to be negatively correlated to bilateral hippocampal volume and high depression score to bilateral gray matter parahippocampal volume. No significant correlations were found between hippocampal or parahippocampal volumes and cognitive functions. CONCLUSION: The present and previous studies showed that morphologic differences do not appear to be due to drug or alcohol abuse. The VBM data partially confirm the group differences seen in the ROI-based method in the medial temporal lobe. The fact that the significantly lower score on the short-term memory test in the PTSD group is not correlated to hippocampal volume may suggest a more general basis for such memory impairment.     

Longitudinal MRI and cognitive change in healthy elderly

Cross-sectional studies of normal aging indicate an association between memory and hippocampal volume, and between executive functioning and subcortical-frontal circuits. Much less is known, however, about the relationship between longitudinal MRI changes and cognitive decline. The authors hypothesized that longitudinal change in memory would be best predicted by change in hippocampal volumes, whereas change in executive functioning would be best predicted by cortical atrophy and progression of MRI markers of cerebrovascular disease. For this study, 50 healthy elderly subjects underwent structural MRI and cognitive testing at baseline and again at follow-up, with a mean follow-up interval of 45 months. Volumetric MRI measures were hippocampus, cortical gray matter, white matter signal hyperintensity (WMSH), and lacunae. Neuropsychological measures were psychometrically robust composite scores of episodic memory (MEM) and executive functioning (EXEC). Hierarchical multiple regression indicated that a decrease in hippocampus was associated with a decline in MEM, whereas decreased cortical gray matter and increased WMSH were independently associated with a decline in EXEC. Results suggest that in normal aging, cognitive functioning declines as cortical gray matter and hippocampus decrease, and WMSH increases. The association between WMSH and EXEC further highlights the cognitive sequealae associated with cerebrovascular disease in normal elderly.     

Higher Gait Variability is Associated with Decreased Parietal Gray Matter Volume Among Healthy Older Adults

The objectives of this study were to examine the association of stride time variability (STV) with gray and white matter volumes in healthy older adults, and to determine the specific location of any parenchymal loss associated with higher STV. A total of 71 participants (mean age 69.0 ± 0.8 years; 59.7 % female) were included in this study. All participants had a 1.0 Tesla 3D T₁-weighted MRI of the brain to measure gray and white matter volumes. STV was measured at steady-state self-selected walking speed using an electronic footswitch system. We found an association between higher STV and lower gray matter volume in the right parietal lobe (e.g., angular gyrus, Brodmann area 39, cluster corrected pFWE = 0.035). There were no significant associations between STV and higher gray matter volume or change in white matter volume. To the best of our knowledge this study is the first to identify a significant association of higher STV with lower right parietal gray matter volume in healthy older adults.     

Brain‐heart interaction in perseverative cognition

The move from the concept of homeostasis to that of allostasis has led reactivity stress research to widen the object of its investigation: from the brief physiological response that occurs when one is facing a stressor to what happens when one is anticipating or recovering from a stressor. A paradigmatic example is represented by perseverative cognition, during which human beings react “as if” they were constantly facing a concrete stressor. The core idea behind this review is that the cognitive inflexibility that characterizes perseverative cognition is reflected in both our body (by increased autonomic nervous system rigidity assessed by heart rate variability; HRV) and our brain (by reduced prefrontal‐amygdala functional connectivity). This is a review of studies conducted in different settings (laboratory, daily life), populations (healthy, major depression, generalized anxiety), location (United States, Europe), and age groups (children, adults) that consistently replicated the association between autonomic, subjective, and behavioral measures of cognitive inflexibility during perseverative cognition. Moreover, compelling neuroimaging data suggest that HRV reduction from pre‐ to post‐induction of perseverative cognition is associated with both structural and functional brain abnormalities reflecting impaired prefrontal inhibitory control over subcortical structures (e.g., diminished prefrontal‐amygdala functional connectivity). The integration of neuroscience techniques with clinical autonomic research has advanced our understanding of the neurobiology of brain–heart interaction during perseverative cognition, potentially yielding to more effective treatment packages. This is clinically relevant if one considers that perseverative cognition is a pervasive transdiagnostic factor that carries prognostic risk for both psychological and somatic health.     

Establishing the validity of a novel passive stress task

Laboratory tasks used to elicit a cardiovascular stress response in the laboratory can involve either active or passive coping. However, in previous work, passive stress tasks often incorporate a distinct physical stress element, such as the handgrip or cold pressor task, meaning observed changes in cardiovascular parameters may be the result of the physical element of the stressor rather than truly reflecting psychological stress. The present study aimed to establish the validity of a psychological passive stressor; one more analogous to active tasks than those previously employed in laboratory studies. Twenty-six young, healthy adults completed a speech task in the laboratory following a resting baseline period. Twelve months later, they were invited back to the laboratory and watched the video recording of their speech. Analyses confirmed that while both tasks elicited significant SBP and DBP change (all ps < .001), only the active task was associated with HR and CO reactivity (both ps < .001), while only the passive task was associated with TPR reactivity (p = .028). Furthermore, the passive stressor was associated with a mixed hemodynamic profile, whereas the active stressor was associated with a clear myocardial profile. This study confirms that watching a video recording of oneself complete a speech task is associated with a more vascular response profile, a response associated with passive coping contexts.     

Emotion suppression affects cardiovascular responses to initial and subsequent laboratory stressors

Objective. The study of anger suppression and risk for cardiovascular disease has relied predominately on inspection of correlations between trait anger‐in and cardiovascular risk factors and disease. This approach tells us little about whether inhibitory processes have anything to do with outcomes, and cannot speak to whether suppression of anger per se affects cardiovascular parameters. Drawing on the broader emotion regulation literature, we examined the effects of experimentally induced anger and general negative emotion in the context of expressive and experiential suppression on cardiovascular responses to initial and subsequent laboratory stressors. Design. Of all participants, 201 healthy participants were randomly assigned to one of six conditions formed by crossing emotion (anxiety, anger) and suppression (experiential, expressive, control) conditions. Methods. Participants completed a mental arithmetic task with anxiety or anger induction under their respective suppression manipulation instructions, and subsequently were exposed to a cold pressor task. Systolic blood pressure (SBP), diastolic blood pressure, and heart rate values were obtained for each experimental epoch. Results. More robust SBP responses to the initial stressor were evidenced for those in the expressive versus the control condition. In response to the subsequent stressor, those in the experiential suppression condition showed the most pronounced SBP responses, suggesting pronounced delayed effects of this type of suppression. Effects of suppression on SBP reactivity were indistinguishable across anxiety and anger conditions. Conclusion. Effortful suppression of negative emotion has immediate and delayed consequences for stress‐induced cardiovascular reactivity. Theoretical and clinical significance of these findings are discussed.     

Working memory performance and thalamus microstructure in healthy subjects

Research on the neural basis of working memory (WM) has generally focused on cortical regions, specifically frontal and parietal areas. Comparatively, evidence of a possible involvement of deep gray matter structures, that are parts of cortico-cortical circuits linking anterior and posterior cortical areas, is far less clear. The goal of the present study is to test the hypothesis that individual structural variations within deep gray matter structures may affect the cortical networks involved in WM. To this aim, a large sample (n=181) of healthy subjects underwent a high-resolution structural magnetic resonance imaging (MRI) and a diffusion tensor imaging (DTI) scan protocol. Data of micro- (mean diffusivity, MD) and macro- (volume) structural variations of six bilateral deep gray matter structures (thalamus, caudate nucleus, putamen, hippocampus, amygdala and pallidum) and lateral ventriculi volume were analyzed in association with score in a WM (the so-called n-back task) and other neuropsychological tasks. Results showed that increased MD of bilateral thalami was the only structural parameter that significantly correlated with reduced WM performance. In particular, a voxel-by-voxel analysis revealed that the greater percentage of voxels showing significant anticorrelation between WM score and MD values were localized in those thalamic nuclei projecting to prefrontal and posterior parietal cortices. Results highlight the specific involvement of thalamus microstructure, not volume, in modulating WM performance, possibly by regulating the connections among cortical areas that are recruited during WM tasks.