scholarly journals Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later

2021 ◽  
Vol 118 (15) ◽  
pp. e2014464118
Author(s):  
Jill M. Goldstein ◽  
Justine E. Cohen ◽  
Klara Mareckova ◽  
Laura Holsen ◽  
Susan Whitfield-Gabrieli ◽  
...  
Keyword(s):  
Sex Differences ◽  
Functional Connectivity ◽  
Proinflammatory Cytokines ◽  
Brain Activity ◽  
In Utero ◽  
Anterior Cingulate ◽  
Hippocampal Activity ◽  
Brain Circuitry ◽  
Anti Inflammatory ◽  
In Utero Development

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring’s risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan.

scholarly journals Linked networks for learning and expressing location-specific threat

2018 ◽  
Vol 115 (5) ◽  
pp. E1032-E1040 ◽  
Author(s):  
Benjamin Suarez-Jimenez ◽  
James A. Bisby ◽  
Aidan J. Horner ◽  
John A. King ◽  
Daniel S. Pine ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Brain Activity ◽  
Anterior Cingulate ◽  
Danger Zone ◽  
Environmental Threats ◽  
Bee Sting ◽  
Defensive Behaviors ◽  
Hippocampal Activity ◽  
Adaptive Ability ◽  
Imminent Threat

Learning locations of danger within our environment is a vital adaptive ability whose neural bases are only partially understood. We examined fMRI brain activity while participants navigated a virtual environment in which flowers appeared and were “picked.” Picking flowers in the danger zone (one-half of the environment) predicted an electric shock to the wrist (or “bee sting”); flowers in the safe zone never predicted shock; and household objects served as controls for neutral spatial memory. Participants demonstrated learning with shock expectancy ratings and skin conductance increases for flowers in the danger zone. Patterns of brain activity shifted between overlapping networks during different task stages. Learning about environmental threats, during flower approach in either zone, engaged the anterior hippocampus, amygdala, and ventromedial prefrontal cortex (vmPFC), with vmPFC–hippocampal functional connectivity increasing with experience. Threat appraisal, during approach in the danger zone, engaged the insula and dorsal anterior cingulate (dACC), with insula–hippocampal functional connectivity. During imminent threat, after picking a flower, this pattern was supplemented by activity in periaqueductal gray (PAG), insula–dACC coupling, and posterior hippocampal activity that increased with experience. We interpret these patterns in terms of multiple representations of spatial context (anterior hippocampus); specific locations (posterior hippocampus); stimuli (amygdala); value (vmPFC); threat, both visceral (insula) and cognitive (dACC); and defensive behaviors (PAG), interacting in different combinations to perform the functions required at each task stage. Our findings illuminate how we learn about location-specific threats and suggest how they might break down into overgeneralization or hypervigilance in anxiety disorders.

scholarly journals Parent–child intervention decreases stress and increases maternal brain activity and connectivity during own baby-cry: An exploratory study

2017 ◽  
Vol 29 (2) ◽  
pp. 535-553 ◽  
Author(s):  
James E. Swain ◽  
S. Shaun Ho ◽  
Katherine L. Rosenblum ◽  
Diana Morelen ◽  
Carolyn J. Dayton ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Parenting Stress ◽  
Brain Activity ◽  
Anterior Cingulate ◽  
Therapeutic Interventions ◽  
Self Awareness ◽  
Brain Scans ◽  
Brain Responses ◽  
Maternal Brain ◽  
Maternal Responses

AbstractParental responses to their children are crucially influenced by stress. However, brain-based mechanistic understanding of the adverse effects of parenting stress and benefits of therapeutic interventions is lacking. We studied maternal brain responses to salient child signals as a function of Mom Power (MP), an attachment-based parenting intervention established to decrease maternal distress. Twenty-nine mothers underwent two functional magnetic resonance imaging brain scans during a baby-cry task designed to solicit maternal responses to child's or self's distress signals. Between scans, mothers were pseudorandomly assigned to either MP (n = 14) or control (n = 15) with groups balanced for depression. Compared to control, MP decreased parenting stress and increased child-focused responses in social brain areas highlighted by the precuneus and its functional connectivity with subgenual anterior cingulate cortex, which are key components of reflective self-awareness and decision-making neurocircuitry. Furthermore, over 13 weeks, reduction in parenting stress was related to increasing child- versus self-focused baby-cry responses in amygdala–temporal pole functional connectivity, which may mediate maternal ability to take her child's perspective. Although replication in larger samples is needed, the results of this first parental-brain intervention study demonstrate robust stress-related brain circuits for maternal care that can be modulated by psychotherapy.

scholarly journals Sex differences in brain development in fetuses and infants who are at low or high likelihood for autism

2021 ◽  
Author(s):  
Luca M Villa ◽  
Sarah Hampton ◽  
Ezra Aydin ◽  
Roger Tait ◽  
Matthew J Leming ◽  
...  
Keyword(s):  
Sex Differences ◽  
Functional Connectivity ◽  
Sexual Differentiation ◽  
Brain Structure ◽  
In Utero ◽  
High Likelihood ◽  
Resting State Functional Connectivity ◽  
Total Brain Volume ◽  
Total Brain ◽  
Brain Structure And Function

Background: It is unknown whether the neural underpinnings of autism are present in utero. In addition, it is unclear whether typical neural sexual differentiation, which is associated with the development of autism, is evident in utero. We longitudinally investigated fetal and infant sex differences in brain structure and function, and differences in brain development in those at low and high likelihood for autism. Here, we use the term "typical" interchangeably with the term "low-autism likelihood". Methods: Participants were longitudinally studied in utero first at 30-33 weeks of gestation, and then as infants 8-12 weeks after birth. We compared total brain volumes and resting-state functional connectivity between 15 female and 15 male low-autism likelihood fetuses (defined as having no first degree autistic relative). We also compared the brain structure and function of these 30 fetuses to a rare group of 11 fetuses (5 females and 6 males) who had an autistic mother or sibling, and therefore a higher likelihood of developing autism. Although a small sample, the high-autism likelihood group are reported as they are challenging to recruit. Additionally, we correlated sex differences in functional connectivity with autism likelihood group differences across the fetal and infant brains. Results: There was a group-by-sex interaction in fetal total brain volume. Typical males, on average, showed faster total brain volume growth in the perinatal period than typical females. The high-autism likelihood group showed lower resting-state functional connectivity at both time-points compared to the typical group, and regions indicating sex differences overlapped with those associated with high-autism likelihood group differences in functional connectivity. Conclusions: In utero sexual differentiation of brain structure was more pronounced in fetuses with a high likelihood for autism. Moreover, sexual differentiation of the fetal and infant brain may overlap with the neural development of autism.

scholarly journals Anterior Cingulate Cortex Activity During Rest Is Related to Alterations in Pain Perception in Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Juan L. Terrasa ◽  
Pedro Montoya ◽  
Carolina Sitges ◽  
Marian van der Meulen ◽  
Fernand Anton ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Pain Intensity ◽  
Anterior Cingulate Cortex ◽  
Resting State ◽  
Pain Perception ◽  
Brain Activity ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Age Related ◽  
Postcentral Gyrus

Alterations in the affective component of pain perception are related to the development of chronic pain and may contribute to the increased vulnerability to pain observed in aging. The present study analyzed age-related changes in resting-state brain activity and their possible relation to an increased pain perception in older adults. For this purpose, we compared EEG current source density and fMRI functional-connectivity at rest in older (n = 20, 66.21 ± 3.08 years) and younger adults (n = 21, 20.71 ± 2.30 years) and correlated those brain activity parameters with pain intensity and unpleasantness ratings elicited by painful stimulation. We found an age-related increase in beta2 and beta3 activity in temporal, frontal, and limbic areas, and a decrease in alpha activity in frontal areas. Moreover, older participants displayed increased functional connectivity in the anterior cingulate cortex (ACC) and the insula with precentral and postcentral gyrus. Finally, ACC beta3 activity was positively correlated with pain intensity and unpleasantness ratings in older, and ACC-precentral/postcentral gyrus connectivity was positively correlated with unpleasantness ratings in older and younger participants. These results reveal that ACC resting-state hyperactivity is a stable trait of brain aging and may underlie their characteristic altered pain perception.

scholarly journals Altered local and matrix functional connectivity in depressed essential tremor patients

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiyue Duan ◽  
Zhou Fang ◽  
Li Tao ◽  
Huiyue Chen ◽  
Xiaoyu Zhang ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Essential Tremor ◽  
Anterior Cingulate Cortex ◽  
Brain Activity ◽  
Cingulate Cortex ◽  
Clinical Depression ◽  
Anterior Cingulate ◽  
Depression Severity ◽  
Correlation Analyses ◽  
Prefrontal Cortices

Abstract Background Depression in essential tremor (ET) has been constantly studied and reported, while the associated brain activity changes remain unclear. Recently, regional homogeneity (ReHo), a voxel-wise local functional connectivity (FC) analysis of resting-state functional magnetic resonance imaging, has provided a promising way to observe spontaneous brain activity. Methods Local FC analyses were performed in forty-one depressed ET patients, 49 non-depressed ET patients and 43 healthy controls (HCs), and then matrix FC and clinical depression severity correlation analyses were further performed to reveal spontaneous neural activity changes in depressed ET patients. Results Compared with the non-depressed ET patients, the depressed ET patients showed decreased ReHo in the bilateral cerebellum lobules IX, and increased ReHo in the bilateral anterior cingulate cortices and middle prefrontal cortices. Twenty-five significant changes of ReHo clusters were observed in the depressed ET patients compared with the HCs, and matrix FC analysis further revealed that inter-ROI FC differences were also observed in the frontal-cerebellar-anterior cingulate cortex pathway. Correlation analyses showed that clinical depression severity was positively correlated with the inter-ROI FC values between the anterior cingulate cortex and bilateral middle prefrontal cortices and was negatively correlated with the inter-ROI FC values of the anterior cingulate cortex and bilateral cerebellum lobules IX. Conclusion Our findings revealed local and inter-ROI FC differences in frontal-cerebellar-anterior cingulate cortex circuits in depressed ET patients, and among these regions, the cerebellum lobules IX, middle prefrontal cortices and anterior cingulate cortices could function as pathogenic structures underlying depression in ET patients.

Age differences in ventromedial prefrontal cortex functional connectivity during socioemotional content processing

2020 ◽  
Vol 48 (7) ◽  
pp. 1-19
Author(s):  
Ryan T. Daley ◽  
Holly J. Bowen ◽  
Eric C. Fields ◽  
Angela Gutchess ◽  
Elizabeth A. Kensinger
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Inferior Frontal Gyrus ◽  
Age Groups ◽  
Emotional Content ◽  
Ventromedial Prefrontal Cortex ◽  
Anterior Cingulate ◽  
Supramarginal Gyrus ◽  
Age Related ◽  
Content Processing

Self-relevance effects are often confounded by the presence of emotional content, rendering it difficult to determine how brain networks functionally connected to the ventromedial prefrontal cortex (vmPFC) are affected by the independent contributions of self-relevance and emotion. This difficulty is complicated by age-related changes in functional connectivity between the vmPFC and other default mode network regions, and regions typically associated with externally oriented networks. We asked groups of younger and older adults to imagine placing emotional and neutral objects in their home or a stranger's home. An age-invariant vmPFC cluster showed increased activation for self-relevant and emotional content processing. Functional connectivity analyses revealed age × self-relevance interactions in vmPFC connectivity with the anterior cingulate cortex. There were also age × emotion interactions in vmPFC functional connectivity with the anterior insula, orbitofrontal gyrus, inferior frontal gyrus, and supramarginal gyrus. Interactions occurred in regions with the greatest differences between the age groups, as revealed by conjunction analyses. Implications of the findings are discussed.

scholarly journals Inhibition of Proinflammatory Cytokines in Cutibacterium acnes-Induced Inflammation in HaCaT Cells by Using Buddleja davidii Aqueous Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Anh Thu Nguyen ◽  
Ki-young Kim
Keyword(s):  
Proinflammatory Cytokines ◽  
Proinflammatory Cytokine ◽  
Treatment Options ◽  
Mapk Signaling ◽  
Cytokine Expression ◽  
Proinflammatory Cytokine Expression ◽  
Cutibacterium Acnes ◽  
Anti Inflammatory ◽  
New Treatment ◽  
Hacat Keratinocyte

Acne is an inflammatory skin disorder; although some anti-inflammatory medicines for treating acne are available in a market, they have considerable side effects; therefore, new treatment options are needed. In the present study, among the 16 aqueous extracts of plants collected from Jeju Island in Korea which are used to test anti-inflammatory activity, B. davidii showed the strong decline of the proinflammatory cytokine expression against the inflammatory process caused by C. acnes in Human HaCaT keratinocyte cells. B. davidii downregulated the expression of 57% of COX-2, 41% of iNOS, and proinflammatory cytokines 29% of TNF-α, 32% of IL-1β, 21% of IL-6, and 35% of IL-8. Furthermore, B. davidii inhibited NF-κB and MAPK signaling cascades in keratinocytes that activated by toll-like receptor 2 (TLR-2) in response to C. acnes. Given those results, B. davidii is a potential agent to reduce the proinflammatory cytokine expression against C. acnes-induced inflammation and might provide an alternative to the current medications.

scholarly journals Applying a Sensing-Enabled System for Ensuring Safe Anterior Cingulate Deep Brain Stimulation for Pain

2019 ◽  
Vol 9 (7) ◽  
pp. 150 ◽  
Author(s):  
Yongzhi Huang ◽  
Binith Cheeran ◽  
Alexander L. Green ◽  
Timothy J. Denison ◽  
Tipu Z. Aziz
Keyword(s):  
Deep Brain Stimulation ◽  
Pain Relief ◽  
Brain Stimulation ◽  
Brain Activity ◽  
Anterior Cingulate ◽  
Chronic Therapy ◽  
Provide Pain Relief ◽  
Surgical Options ◽  
Effective Pain Relief ◽  
Deep Brain

Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain activity and to guide safe DBS programming. A sensing-enabled neurostimulator (Activa PC + S) allowing wireless recording through the stimulating electrodes was chronically implanted in three patients. Stimulation patterns with different amplitude levels and variable ramping rates were tested to investigate whether these patterns could provide pain relief without triggering after-discharges (ADs) within local field potentials (LFPs) recorded in the ACC. In the absence of ramping, AD activity was detected following stimulation at amplitude levels below those used in chronic therapy. Adjustment of stimulus cycling patterns, by slowly ramping on/off (8-s ramp duration), was able to prevent ADs at higher amplitude levels while maintaining effective pain relief. The absence of AD activity confirmed from the implant was correlated with the absence of clinical seizures. We propose that AD activity in the ACC could be a biomarker for the likelihood of seizures in these patients, and the application of sensing-enabled techniques has the potential to advance safer brain stimulation therapies, especially in novel targets.

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