1,534 results
Search Results
2. Review Paper: Role of Nitric Oxide on Dopamine Release and Morphine-Dependency
- Author
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Amir Arash Motahari, Hedayat Sahraei, and Gholam Hossein Meftahi
- Subjects
Nitric oxide ,Opioid ,Amygdala ,Ventral tegmental area ,Nucleus accumbens ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The catastrophic effects of opioids use on public health and the economy are documented clearly in numerous studies. Repeated morphine administration can lead to either a decrease (tolerance) or an increase (sensitization) in its behavioral and rewarding effects. Morphine-induced sensitization is a major problem and plays an important role in abuse of the opioid drugs. Studies reported that morphine may exert its effects by the release of nitric oxide (NO). NO is a potent neuromodulator, which is produced by nitric oxide synthase (NOS). However, the exact role of NO in the opioid-induced sensitization is unknown. In this study, we reviewed the role of NO on opioid-induced sensitization in 2 important, rewarding regions of the brain: nucleus accumbens and ventral tegmentum. In addition, we focused on the contribution of NO on opioid-induced sensitization in the limbic system.
- Published
- 2016
3. Utilization of a rodent model to examine the neurological effects of early life adversity on adolescent pain sensitivity.
- Author
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Salberg S, Noel M, Burke NN, Vinall J, and Mychasiuk R
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- Animals, Animals, Newborn, Disease Models, Animal, Female, Gene Expression genetics, Male, Maternal Deprivation, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Telomere metabolism, Amygdala metabolism, Anxiety genetics, Anxiety immunology, Anxiety metabolism, Anxiety physiopathology, Behavior, Animal physiology, Chronic Pain genetics, Chronic Pain immunology, Chronic Pain metabolism, Chronic Pain physiopathology, Hippocampus metabolism, Nociception physiology, Prefrontal Cortex metabolism, Stress, Psychological genetics, Stress, Psychological immunology, Stress, Psychological metabolism, Stress, Psychological physiopathology
- Abstract
All children experience pain, and although many recover quickly, some go on to develop chronic pain. Adolescent chronic pain is a growing epidemic. It is unknown why some adolescents recover without incident and others experience persistent pain. Although unexplored, early life adversity may contribute to the development and maintenance of chronic pain. This study investigated the effects and underlying neurobiological mechanisms of an early life stressor on nociceptive (pain) sensitivity and emotional function in male and female Sprague-Dawley rats. Using maternal separation (MS) as an established model of early life stress, we addressed two aims: investigation of the effects of MS on behavior (anxiety and pain sensitivity), and investigation of the effects of MS on mRNA and pathophysiological changes associated with an acutely painful stimulus. Our results indicate that MS increased anxiety-like behavior and altered nociceptive responsivity in adolescent rats, with decreased mechanical withdrawal thresholds indicative of heightened and prolonged pain-related behavior. The MS groups also demonstrated increased expression of genes involved in regulating the stress and fight-or-flight response, mood, and neuroplasticity; as well as increased levels of inflammatory markers. We conclude that nociception, both at the behavioral and molecular level, is altered in response to the MS stressor., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2020
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4. Spatial distribution of beta-klotho mRNA in the mouse hypothalamus, hippocampal region, subiculum, and amygdala.
- Author
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Bono BS, Koziel Ly NK, Miller PA, Williams-Ikhenoba J, Dumiaty Y, and Chee MJ
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- Animals, Cerebral Cortex, Hypothalamus, Mice, RNA, Messenger, Amygdala, Hippocampus
- Abstract
Beta-klotho (KLB) is a coreceptor required for endocrine fibroblast growth factor (FGF) 15/19 and FGF21 signaling in the brain. Klb is prominent within the hypothalamus, which is consistent with its metabolic functions, but diverse roles for Klb are now emerging. Central Klb expression is low but discrete and may govern FGF-targeted sites. However, given its low expression, it is unclear if Klb mRNA is more widespread. We performed in situ hybridization to label Klb mRNA to generate spatial maps capturing the distribution and levels of Klb within the mouse hypothalamus, hippocampal region, subiculum, and amygdala. Semiquantitative analysis revealed that Klb-labeled cells may express low, medium, or high levels of Klb mRNA. Hypothalamic Klb hybridization was heterogeneous and varied rostrocaudally within the same region. Most Klb-labeled cells were found in the lateral hypothalamic zone, but the periventricular hypothalamic region, including the suprachiasmatic nucleus, contained the greatest proportion of cells expressing medium or high Klb levels. We also found heterogeneous Klb hybridization in the amygdala and subiculum, where Klb was especially distinct within the central amygdalar nucleus and ventral subiculum, respectively. By contrast, Klb-labeled cells in the hippocampal region only expressed low levels of Klb and were typically found in the pyramidal layer of Ammon's horn or dentate gyrus. The Klb-labeled regions identified in this study are consistent with reported roles of Klb in metabolism, taste preference, and neuroprotection. However, additional identified sites, including within the hypothalamus and amygdala, may suggest novel roles for FGF15/19 or FGF21 signaling., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
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5. Review Paper: Role of Nitric Oxide on Dopamine Release and Morphine-Dependency.
- Author
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Motahari, Amir Arash, Sahraei, Hedayat, and Meftahi, Gholam Hossein
- Subjects
- *
NITRIC oxide , *DOPAMINE , *MORPHINE abuse , *THERAPEUTICS - Abstract
The catastrophic effects of opioids use on public health and the economy are documented clearly in numerous studies. Repeated morphine administration can lead to either a decrease (tolerance) or an increase (sensitization) in its behavioral and rewarding effects. Morphine-induced sensitization is a major problem and plays an important role in abuse of the opioid drugs. Studies reported that morphine may exert its effects by the release of nitric oxide (NO). NO is a potent neuromodulator, which is produced by nitric oxide synthase (NOS). However, the exact role of NO in the opioid-induced sensitization is unknown. In this study, we reviewed the role of NO on opioid-induced sensitization in 2 important, rewarding regions of the brain: nucleus accumbens and ventral tegmentum. In addition, we focused on the contribution of NO on opioid-induced sensitization in the limbic system. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
6. Comparative neuroanatomical study of the amygdala and fear conditioning in Nigerian breeds of Artiodactyla: Sheep (Uda) and goats (Red Sokoto).
- Author
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George I, Alawa J, Akpulu P, and Alawa C
- Subjects
- Acoustic Stimulation, Amygdala physiology, Animals, Goats physiology, Nigeria, Sheep physiology, Amygdala anatomy & histology, Conditioning, Classical physiology, Fear physiology, Goats anatomy & histology, Sheep anatomy & histology
- Abstract
The aim of this study was to evaluate fear condition responses in sheep and goat and to relate this to the neuroarchitecture of their amygdala. Forty adult sheep (Uda breed) and 40 adult goats (Red Sokoto breed) were fear-conditioned by associating the sound of a car horn (neutral stimuli) with water spray (aversive stimuli) and the fear response was determined by direct observation of the behavior of the sheep and goats and measuring their flight distances and escape time. Eight groups were studied, each comprising of 10 animals (five sheep and five goats). Goats and sheep were tested alternately in the morning of every day of the week for three consecutive weeks, in which 4 days was used for habituation and 3 days for testing. Histologically, neurons in the central and basolateral complex of the amygdala were studied and analyzed using Nissl and golgi staines. Behaviorally, goats elicited an active avoidance response expressed as flight with concomitant intense flight distances (p < .001) compared to sheep. Although, sheep had larger brain parameters, it showed attenuated basolateral amygdala cytoarchitecture consistent with reduced fear perception and response. Goats had significantly more densely distributed pyramidal and spiny stellate neurons in the basolateral amygdala while sheep showed more non-pyramidal and aspiny neurons. These results provide interesting practical perspectives on how adaptions in the amygdala coincides with alterations in fear conditioning in domestic animals and may be the basis for the higher incidence of the sheep in automobile accidents than goats in developing countries especially Africa., (© 2020 American Association for Anatomy.)
- Published
- 2021
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7. Amygdala connectivity is associated with withdrawn/depressed behavior in a large sample of children from the Adolescent Brain Cognitive Development (ABCD) Study®.
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Thomas E, Juliano A, Owens M, Cupertino RB, Mackey S, Hermosillo R, Miranda-Dominguez O, Conan G, Ahmed M, Fair DA, Graham AM, Goode NJ, Kandjoze UP, Potter A, Garavan H, and Albaugh MD
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- Humans, Child, Male, Female, Adolescent, Neural Pathways physiopathology, Neural Pathways diagnostic imaging, Neural Pathways growth & development, Amygdala diagnostic imaging, Amygdala physiopathology, Magnetic Resonance Imaging, Depression diagnostic imaging, Depression physiopathology, Depression psychology
- Abstract
Many psychopathologies tied to internalizing symptomatology emerge during adolescence, therefore identifying neural markers of internalizing behavior in childhood may allow for early intervention. We utilized data from the Adolescent Brain and Cognitive Development (ABCD) Study® to evaluate associations between cortico-amygdalar functional connectivity, polygenic risk for depression (PRS
D ), traumatic events experienced, internalizing behavior, and internalizing subscales: withdrawn/depressed behavior, somatic complaints, and anxious/depressed behaviors. Data from 6371 children (ages 9-11) were used to analyze amygdala resting-state fMRI connectivity to Gordon parcellation based whole-brain regions of interest (ROIs). Internalizing behaviors were measured using the parent-reported Child Behavior Checklist. Linear mixed-effects models were used to identify patterns of cortico-amygdalar connectivity associated with internalizing behaviors. Results indicated left amygdala connections to auditory, frontoparietal network (FPN), and dorsal attention network (DAN) ROIs were significantly associated with withdrawn/depressed symptomatology. Connections relevant for withdrawn/depressed behavior were linked to social behaviors. Specifically, amygdala connections to DAN were associated with social anxiety, social impairment, and social problems. Additionally, an amygdala connection to the FPN ROI and the auditory network ROI was associated with social anxiety and social problems, respectively. Therefore, it may be important to account for social behaviors when looking for brain correlates of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
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8. Progressive long-term synaptic depression at cortical inputs into the amygdala.
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Psyrakis D, Jasiewicz J, Wehrmeister M, Bonni K, Lutz B, and Kodirov SA
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- Animals, Male, Pyramidal Cells physiology, Electric Stimulation, Rats, Rats, Wistar, Cerebral Cortex physiology, Neural Pathways physiology, In Vitro Techniques, Long-Term Synaptic Depression physiology, Excitatory Postsynaptic Potentials physiology, Patch-Clamp Techniques, Amygdala physiology
- Abstract
The convergence of conditioned and unconditioned stimuli (CS and US) into the lateral amygdala (LA) serves as a substrate for an adequate fear response in vivo. This well-known Pavlovian paradigm modulates the synaptic plasticity of neurons, as can be proved by the long-term potentiation (LTP) phenomenon in vitro. Although there is an increasing body of evidence for the existence of LTP in the amygdala, only a few studies were able to show a reliable long-term depression (LTD) of excitation in this structure. We have used coronal brain slices and conducted patch-clamp recordings in pyramidal neurons of the lateral amygdala (LA). After obtaining a stable baseline excitatory postsynaptic current (EPSC) response at a holding potential of -70 mV, we employed a paired-pulse paradigm at 1 Hz at the same membrane potential and could observe a reliable LTD. The different durations of stimulation (ranging between 1.5-24 min) were tested first in the same neuron, but the intensity was kept constant. The latter paradigm resulted in a step-wise LTD with a gradually increasing magnitude under these conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). All rights reserved.)
- Published
- 2024
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9. Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast.
- Author
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Arjol D, Agüera ADR, Hagen C, and Papini MR
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- Animals, Male, Rats, Rats, Wistar, Consummatory Behavior physiology, Reward, Amygdala metabolism, Amygdala physiology, Proto-Oncogene Proteins c-fos metabolism
- Abstract
The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala's involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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10. Mating-induced release of oxytocin in the mouse lateral septum: Implications for social fear extinction.
- Author
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Grossmann CP, Sommer C, Fahliogullari IB, Neumann ID, and Menon R
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- Animals, Male, Mice, Female, Social Behavior, Anxiety metabolism, Receptors, Oxytocin metabolism, Septal Nuclei metabolism, Septal Nuclei drug effects, Ejaculation physiology, Copulation physiology, Septum of Brain metabolism, Septum of Brain physiology, Mice, Inbred C57BL, Behavior, Animal physiology, Behavior, Animal drug effects, Fear physiology, Oxytocin metabolism, Extinction, Psychological physiology, Sexual Behavior, Animal physiology, Amygdala metabolism
- Abstract
In mammals, some physiological conditions are associated with the high brain oxytocin (OXT) system activity. These include lactation in females and mating in males and females, both of which have been linked to reduced stress responsiveness and anxiolysis. Also, in a murine model of social fear conditioning (SFC), enhanced brain OXT signaling in lactating mice, specifically in the lateral septum (LS), was reported to underlie reduced social fear expression. Here, we studied the effects of mating in male mice on anxiety-related behaviour, social (and cued) fear expression and its extinction, and the activity of OXT neurons reflected by cFos expression and OXT release in the LS and amygdala. We further focused on the involvement of brain OXT in the mating-induced facilitation of social fear extinction. We could confirm the anxiolytic effect of mating in male mice irrespective of the occurrence of ejaculation. Further, we found that only successful mating resulting in ejaculation (Ej
+ ) facilitated social fear extinction, whereas mating without ejaculation (Ej- ) did not. In contrast, mating did not affect cues fear expression. Using the cellular activity markers cFos and pErk, we further identified the ventral LS (vLS) as a potential region participating in the effect of ejaculation on social fear extinction. In support, microdialysis experiments revealed a rise in OXT release within the LS, but not the amygdala, during mating. Finally, infusion of an OXT receptor antagonist into the LS before mating or into the lateral ventricle (icv) after mating demonstrated a significant role of brain OXT receptor-mediated signaling in the mating-induced facilitation of social fear extinction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rohit Menon reports was provided by German Research Foundation. Inga D. Neumann reports financial support was provided by German Research Foundation. Cindy Grossmann reports financial support was provided by German Research Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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11. An emotional control approach to grid-connected DFIG based wind turbine
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Velpula, Manikanta Raju and Kona, Hanumath Phani Shree
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- 2024
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12. Functional connectivity of amygdala subregions predicts vulnerability to depression following the COVID-19 pandemic
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Yun Wang, Yuan Zhou, Xiongying Chen, Jian Cui, Yuan Feng, Shudong Zhang, Rui Liu, Zhifang Zhang, Gang Wang, and Jingjing Zhou
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Vulnerability ,Precuneus ,behavioral disciplines and activities ,Amygdala ,Lingual gyrus ,Neuroimaging ,mental disorders ,medicine ,Humans ,Pandemics ,Depression (differential diagnoses) ,Retrospective Studies ,Depressive Disorder, Major ,Resting-state functional connectivity ,medicine.diagnostic_test ,Depression ,SARS-CoV-2 ,Postcentral gyrus ,business.industry ,COVID-19 ,medicine.disease ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Clinical Psychology ,medicine.anatomical_structure ,nervous system ,Major depressive disorder ,Functional magnetic resonance imaging ,business ,Research Paper ,Clinical psychology - Abstract
Background The amygdala is vital in processing psychological stress and predicting vulnerability or resilience to stress-related disorders. This study aimed to build the link between functional magnetic resonance imaging data obtained before the stress event and the subsequent stress-related depressive symptoms. Methods Neuroimaging data obtained before the coronavirus disease 2019 pandemic from 39 patients with major depressive disorder (MDD) and 61 health controls (HCs) were used in this study. The participants were divided retrospectively into four groups in accordance with the severity of depressive symptoms during the pandemic: remitted patients, non-remitted patients, depressed HCs (HCd) and non-depressed HCs (HCnd). Seed-based resting-state functional connectivity (rsFC) analyses of the amygdala and its subregions, including the centromedial (CM), the basolateral and the superficial (SF), were performed. Results Vulnerability to depression was suggested by decreased rsFC between the left CM amygdala and the bilateral lingual gyrus in the HCd group compared with the HCnd group, and decreased rsFC of the left CM or right SF amygdala with the precuneus and the postcentral gyrus in the HCd group compared with patients with MDD. No evidence supported the rsFC of the amygdala or its subregions as a biomarker for the resilience of patients with MDD to stress under antidepressant treatment. Limitations Smaller sample size and no longitudinal neuroimaging data. Conclusions Our findings suggested that the rsFC of amygdala subregions may represent a neurobiological marker of vulnerability to depression following stress.
- Published
- 2022
13. Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERβ and oxytocin of C57BL/6J female mice
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Zhen Tian, Bin Yu, Xiao-Xia Cheng, Feng-Qin He, Zi-Jian Wang, Mei-Yang Fan, Rui-Juan Lai, Bing-Jie Yan, Yu-Nan Hui, Ming-Juan Yang, and Xin Chen
- Subjects
medicine.medical_specialty ,OF, open field test ,TRE, treadmill exercise ,E2, 17-beta-oestradiol ,Estrogen receptor ,Treadmill exercise ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Amygdala ,Supraoptic nucleus ,Open field ,HRP, horseradishperoxidase ,HTRE, higher speed TRE ,Chronic variable moderate stress (CVMS) ,mPOA, medial preopticarea ,Estrogen receptor β (ERβ) ,Internal medicine ,Estrogen receptor α (ERα) ,Treadmill exercise (TRE) ,ERβ-IRs, estrogen receptor β immunoreactive neurons ,Medicine ,BNST, bed nucleus of the stria terminalis ,LMTRE, low-moderate speed TRE ,business.industry ,CVMS, chronic variable moderate stress ,General Neuroscience ,MeA, medial amygdaloid nucleus ,ELISA, enzyme-linked immunosorbent assay ,PBS, phosphatebufferedsolution ,EPM, elevated plusmazetest ,HPA, hypothalamic–pituitary–adrenal ,SON, supraoptic nucleus ,Stria terminalis ,medicine.anatomical_structure ,Endocrinology ,Oxytocin ,OT-IRs, Oxytocin immunoreactive neurons ,ERα-IRs, estrogen receptors αimmunoreactive neurons ,Oxytocin (OT) ,business ,Nucleus ,hormones, hormone substitutes, and hormone antagonists ,Research Paper ,PVN, paraventricular nucleus ,medicine.drug ,RC321-571 - Abstract
Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors β immunoreactive neurons (ERβ-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there’s increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERβ-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERβ/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions., Highlights • CVMS/LMTRE did not show anxiety. • noCVMS/LMTRE did not show anxiety. • ERβ/ERα ratio decreas anxiety. • OT decreas anxiety.
- Published
- 2021
14. Resting-state functional connectivity of the amygdala subregions in unmedicated patients with obsessive–compulsive disorder before and after cognitive behavioural therapy
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Xiangyun Yang, Jian Gao, Rui Liu, Pengchong Wang, Zhanjiang Li, Yuan Zhou, Fanqiang Meng, and Xiongying Chen
- Subjects
Obsessive-Compulsive Disorder ,medicine.medical_specialty ,Audiology ,behavioral disciplines and activities ,Amygdala ,Neural Pathways ,mental disorders ,medicine ,Humans ,Pharmacology (medical) ,Association (psychology) ,Biological Psychiatry ,Brain Mapping ,Cognitive Behavioral Therapy ,Resting state fMRI ,business.industry ,Functional connectivity ,Parietal lobe ,Cognition ,Magnetic Resonance Imaging ,humanities ,Psychiatry and Mental health ,medicine.anatomical_structure ,Cerebral cortex ,business ,Research Paper ,Basolateral amygdala - Abstract
Background Cognitive behavioural therapy (CBT) is considered an effective first-line treatment for obsessive-compulsive disorder (OCD). However, the neural basis of CBT for OCD has not yet been elucidated. The role of the amygdala in OCD and its functional coupling with the cerebral cortex have received increasing attention, and may provide new understanding of the neural basis of CBT for OCD. Methods We acquired baseline resting-state functional MRI (fMRI) scans from 45 unmedicated patients with OCD and 40 healthy controls; we then acquired another wave of resting-state fMRI scans from the patients with OCD after 12 weeks of CBT. We performed seed-based resting-state functional connectivity analyses of the amygdala subregions to examine changes in patients with OCD as a result of CBT. Results Compared to healthy controls, patients with OCD showed significantly increased resting-state functional connectivity at baseline between the left basolateral amygdala and the right middle frontal gyrus, and between the superficial amygdala and the right cuneus. In patients with OCD who responded to CBT, we found decreased resting-state functional connectivity after CBT between the amygdala subregions and the visual association cortices and increased resting-state functional connectivity between the amygdala subregions and the right inferior parietal lobe. Furthermore, these changes in resting-state functional connectivity were positively associated with changes in scores on the compulsion or obsession subscales of the Yale-Brown Obsessive-Compulsive Scale. Limitations Because of the lack of a second scan for healthy controls after 12 weeks, our results may have been confounded by other variables. Conclusion Our findings yield insights into the pathophysiology of OCD; they also reveal the potential neural changes elicited by CBT, and thus have implications for guiding effective treatment strategies with CBT for OCD.
- Published
- 2021
15. Social-Single Prolonged Stress affects contextual fear conditioning in male and female Wistar rats: Molecular insights in the amygdala.
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Jung JTK, Marques LS, Brambila CA, da Cruz Weber Fulco B, Nogueira CW, and Zeni G
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- Animals, Male, Female, Rats, Disease Models, Animal, Stress Disorders, Post-Traumatic metabolism, Stress Disorders, Post-Traumatic psychology, Conditioning, Classical drug effects, Conditioning, Classical physiology, Conditioning, Psychological drug effects, Conditioning, Psychological physiology, Selective Serotonin Reuptake Inhibitors pharmacology, Disks Large Homolog 4 Protein, Receptors, AMPA, Fear drug effects, Fear physiology, Rats, Wistar, Fluoxetine pharmacology, Amygdala drug effects, Amygdala metabolism, Stress, Psychological metabolism
- Abstract
Stress exposure can lead to post-traumatic stress disorder (PTSD) in male and female rats. Social-Single Prolonged Stress (SPS) protocol has been considered a potential PTSD model. This study aimed to pharmacologically validate the Social-SPS as a PTSD model in male and female rats. Male and female Wistar rats (60-day-old) were exposed to Social-SPS protocol and treated with fluoxetine (10 mg/Kg) or saline solution intraperitoneally 24 h before euthanasia. Two cohorts of animals were used; for cohort 1, male and female rats were still undisturbed until day 7 post-Social-SPS exposure, underwent locomotor and conditioned fear behaviors, and were euthanized on day 9. Animals of cohort 2 were subjected to the same protocol but were re-exposed to contextual fear behavior on day 14. Results showed that fluoxetine-treated rats gained less body weight than control and Social-SPS in both sexes. Social-SPS effectively increased the freezing time in male and female rats on day eight but not on day fourteen. Fluoxetine blocked the increase of freezing in male and female rats on day 8. Different mechanisms for fear behavior were observed in males, such as Social-SPS increased levels of glucocorticoid receptors and Beclin-1 in the amygdala. Social-SPS was shown to increase the levels of NMDA2A, GluR-1, PSD-95, and CAMKII in the amygdala of female rats. No alterations were observed in the amygdala of rats on day fourteen. The study revealed that Social-SPS is a potential PTSD protocol applicable to both male and female rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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16. Dynamic Amygdala Nuclei Alterations in Relation to Weight Status in Anorexia Nervosa Are Mediated by Leptin.
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Wronski ML, Bernardoni F, Bahnsen K, Seidel M, Arold D, Doose A, Steinhäuser JL, Borucki K, Breithaupt L, Lawson EA, Holsen LM, Weidner K, Roessner V, King JA, Plessow F, and Ehrlich S
- Subjects
- Adolescent, Adult, Female, Humans, Young Adult, Body Weight, Longitudinal Studies, Weight Gain physiology, Amygdala diagnostic imaging, Amygdala pathology, Amygdala physiopathology, Anorexia Nervosa physiopathology, Anorexia Nervosa diagnostic imaging, Anorexia Nervosa pathology, Leptin blood, Leptin metabolism, Magnetic Resonance Imaging
- Abstract
Objective: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels., Method: T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n = 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n = 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n = 271) using linear mixed effects models., Results: Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d = 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei., Conclusion: Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN., Plain Language Summary: The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weight-restoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course., Diversity & Inclusion Statement: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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17. Infant attachment does not depend on neonatal amygdala and hippocampal structure and connectivity.
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Jiménez-Sánchez L, Blesa Cábez M, Vaher K, Corrigan A, Thrippleton MJ, Bastin ME, Quigley AJ, Fletcher-Watson S, and Boardman JP
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- Humans, Male, Female, Infant, Newborn, Infant, Neural Pathways, Infant, Premature, Magnetic Resonance Imaging methods, Diffusion Tensor Imaging methods, Infant Behavior physiology, Hippocampus, Amygdala diagnostic imaging, Object Attachment
- Abstract
Infant attachment is an antecedent of later socioemotional abilities, which can be adversely affected by preterm birth. The structural integrity of amygdalae and hippocampi may subserve attachment in infancy. We aimed to investigate associations between neonatal amygdalae and hippocampi structure and their whole-brain connections and attachment behaviours at nine months of age in a sample of infants enriched for preterm birth. In 133 neonates (median gestational age 32 weeks, range 22.14-42.14), we calculated measures of amygdala and hippocampal structure (volume, fractional anisotropy, mean diffusivity, neurite dispersion index, orientation dispersion index) and structural connectivity, and coded attachment behaviours (distress, fretfulness, attentiveness to caregiver) from responses to the Still-Face Paradigm at nine months. After multiple comparisons correction, there were no significant associations between neonatal amygdala or hippocampal structure and structural connectivity and attachment behaviours: standardised β values - 0.23 to 0.18, adjusted p-values > 0.40. Findings indicate that the neural basis of infant attachment in term and preterm infants is not contingent on the structure or connectivity of the amygdalae and hippocampi in the neonatal period, which implies that it is more widely distributed in early life and or that network specialisation takes place in the months after hospital discharge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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18. Structural characteristics of amygdala subregions in type 2 diabetes mellitus.
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Qiu W, Yue X, Huang H, Ge L, Lu W, Cao Z, Rao Y, Tan X, Wang Y, Wu J, Chen Y, Qiu S, and Li G
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- Humans, Male, Female, Middle Aged, Adult, Aged, Hippocampus pathology, Hippocampus diagnostic imaging, Thalamus diagnostic imaging, Thalamus pathology, Diabetes Mellitus, Type 2 pathology, Amygdala pathology, Amygdala diagnostic imaging, Magnetic Resonance Imaging, Depression diagnostic imaging, Depression pathology
- Abstract
Type 2 diabetes mellitus (T2DM) patients often suffer from depressive symptoms, which seriously affect cooperation in treatment and nursing. The amygdala plays a significant role in depression. This study aims to explore the microstructural alterations of the amygdala in T2DM and to investigate the relationship between the alterations and depressive symptoms. Fifty T2DM and 50 healthy controls were included. Firstly, the volumes of subcortical regions and subregions of amygdala were calculated by FreeSurfer. Covariance analysis (ANCOVA) was conducted between the two groups with covariates of age, sex, and estimated total intracranial volume to explore the differences in volume of subcortical regions and subregions of amygdala. Furthermore, the structural covariance within the amygdala subregions was performed. Moreover, we investigate the correlation between depressive symptoms and the volume of subcortical regions and amygdala subregions in T2DM. We observed a reduction in the volume of the bilateral cortico-amygdaloid transition area, left basal nucleus, bilateral accessory basal nucleus, left anterior amygdaloid area of amygdala, the left thalamus and left hippocampus in T2DM. T2DM patients showed decreased structural covariance connectivity between left paralaminar nucleus and the right central nucleus. Moreover, there was a negative correlation between self-rating depression scale scores and the volume of the bilateral cortico-amygdaloid transition area in T2DM. This study reveals extensive structural alterations in the amygdala subregions of T2DM patients. The reduction in the volume of the bilateral cortico-amygdaloid transition area may be a promising imaging marker for early recognition of depressive symptoms in T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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19. Cannabis use and resting state functional connectivity in adolescent bipolar disorder
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Megan Hird, Bradley J. MacIntosh, Benjamin I. Goldstein, Mikaela Dimick, and Alysha Sultan
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Male ,Bipolar Disorder ,Adolescent ,Rest ,Prefrontal Cortex ,Nucleus accumbens ,Amygdala ,Nucleus Accumbens ,Reward ,Neural Pathways ,mental disorders ,medicine ,Humans ,Pharmacology (medical) ,Bipolar disorder ,Biological Psychiatry ,Cannabis ,Resting state fMRI ,business.industry ,Functional connectivity ,Parietal lobe ,Cannabis use ,medicine.disease ,Psychiatry and Mental health ,medicine.anatomical_structure ,Female ,Marijuana Use ,Orbitofrontal cortex ,business ,Research Paper ,Clinical psychology - Abstract
Background Adolescents with bipolar disorder have high rates of cannabis use, and cannabis use is associated with increased symptom severity and treatment resistance in bipolar disorder. Studies have identified anomalous resting-state functional connectivity among reward networks in bipolar disorder and cannabis use independently, but have yet to examine their convergence. Methods Participants included 134 adolescents, aged 13 to 20 years: 40 with bipolar disorder and lifetime cannabis use, 31 with bipolar disorder and no history of cannabis use, and 63 healthy controls without lifetime cannabis use. We used a seed-to-voxel analysis to assess the restingstate functional connectivity of the amygdala, the nucleus accumbens and the orbitofrontal cortex, regions implicated in bipolar disorder and cannabis use. We used a generalized linear model to explore bivariate correlations for each seed, controlling for age and sex. Results We found 3 significant clusters. Resting-state functional connectivity between the left nucleus accumbens seed and the left superior parietal lobe was negative in adolescents with bipolar disorder and no history of cannabis use, and positive in healthy controls. Resting-state functional connectivity between the right orbitofrontal cortex seed and the right lateral occipital cortex was positive in adolescents with bipolar disorder and lifetime cannabis use, and negative in healthy controls and adolescents with bipolar disorder and no history of cannabis use. Resting-state functional connectivity between the right orbitofrontal cortex seed and right occipital pole was positive in adolescents with bipolar disorder and lifetime cannabis use, and negative in adolescents with bipolar disorder and no history of cannabis use. Limitations The study did not include a cannabis-using control group. Conclusion This study provides preliminary evidence of cannabis-related differences in functional reward circuits in adolescents with bipolar disorder. Further studies are necessary to evaluate whether the present findings reflect consequences of or predisposition to cannabis use.
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- 2021
20. Active role of the central amygdala in widespread mechanical sensitization in rats with facial inflammatory pain
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Fusao Kato, Mariko Sugimoto, Ryota Tokunaga, Manami Yajima, Yukari Takahashi, and Yae K. Sugimura
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Male ,Pain Threshold ,medicine.medical_specialty ,Inflammation ,von Frey filament test ,Amygdala ,Mechanical allodynia ,Adeno-associated virus ,Facial Pain ,Internal medicine ,Medicine ,Premovement neuronal activity ,Animals ,Rats, Wistar ,Sensitization ,Neurons ,Designer receptor exclusively activated by a designer drug ,GABAergic neurons ,business.industry ,Central nucleus of the amygdala ,Central Amygdaloid Nucleus ,Chronic pain ,Central sensitization ,medicine.disease ,Rats ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,Nociception ,Endocrinology ,Neurology ,nervous system ,Latent orofacial formalin model ,VGAT-cre rat ,Body region ,Neurology (clinical) ,Clozapine-N-Oxide ,medicine.symptom ,Amygdala lateralization ,business ,Latent inflammatory pain ,psychological phenomena and processes ,Research Paper ,Calcitonin gene–related peptide receptor - Abstract
Supplemental Digital Content is Available in the Text. Activity of gamma-aminobutyric acid-ergic neurons in the right-side central amygdala determines ectopic mechanical allodynia in the bilateral hind limbs in rats with orofacial inflammation., Widespread or ectopic sensitization is a hallmark symptom of chronic pain, characterized by aberrantly enhanced pain sensitivity in multiple body regions remote from the site of original injury or inflammation. The central mechanism underlying widespread sensitization remains unidentified. The central nucleus of the amygdala (also called the central amygdala, CeA) is well situated for this role because it receives nociceptive information from diverse body sites and modulates pain sensitivity in various body regions. In this study, we examined the role of the CeA in a novel model of ectopic sensitization of rats. Injection of formalin into the left upper lip resulted in latent bilateral sensitization in the hind paw lasting >13 days in male Wistar rats. Chemogenetic inhibition of gamma–aminobutyric acid-ergic neurons or blockade of calcitonin gene-related peptide receptors in the right CeA, but not in the left, significantly attenuated this sensitization. Furthermore, chemogenetic excitation of gamma-aminobutyric acid-ergic neurons in the right CeA induced de novo bilateral hind paw sensitization in the rats without inflammation. These results indicate that the CeA neuronal activity determines hind paw tactile sensitivity in rats with remote inflammatory pain. They also suggest that the hind paw sensitization used in a large number of preclinical studies might not be simply a sign of the pain at the site of injury but rather a representation of the augmented CeA activity resulting from inflammation/pain in any part of the body or from activities of other brain regions, which has an active role of promoting defensive/protective behaviors to avoid further bodily damage.
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- 2021
21. Neural effects of antidepressant medication and psychological treatments: a quantitative synthesis across three meta-analyses
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Lisa Feldman Barrett, Kristen A. Lindquist, Tim Dalgleish, Yina Ma, Lindsey Marwood, Camilla L. Nord, and Ajay B. Satpute
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Paper ,Affect (psychology) ,Amygdala ,050105 experimental psychology ,cognitive–behavioural therapies ,03 medical and health sciences ,0302 clinical medicine ,anxiety disorders ,Neuroimaging ,Humans ,Medicine ,Academic Psychiatry ,0501 psychology and cognitive sciences ,skin and connective tissue diseases ,Prefrontal cortex ,Depressive Disorder, Major ,Mood Disorders ,business.industry ,Panic disorder ,05 social sciences ,imaging ,Antidepressants ,medicine.disease ,Antidepressive Agents ,Psychotherapy ,Psychiatry and Mental health ,medicine.anatomical_structure ,Major depressive disorder ,Antidepressant ,sense organs ,depressive disorders ,business ,Neurocognitive ,Neuroscience ,030217 neurology & neurosurgery - Abstract
BackgroundInfluential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes.AimsTo test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network.MethodWe employed a quantitative synthesis of three meta-analyses (n = 4206). First, we assessed the common and distinct neural changes evoked by antidepressant medication and psychotherapy, by contrasting two comparable meta-analyses reporting the neural effects of these treatments. Both meta-analyses included patients with affective disorders, including major depressive disorder, generalised anxiety disorder and panic disorder. The majority were assessed using negative-valence tasks during neuroimaging. Next, we assessed whether the neural changes evoked by antidepressants and psychotherapy overlapped with the brain's affect network, using data from a third meta-analysis of affect-based neural activation.ResultsNeural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network.ConclusionsThis supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action.
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- 2021
22. Effects of childhood adversity on the volumes of the amygdala subnuclei and hippocampal subfields in individuals with major depressive disorder
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Peter Seres, Arash Aghamohammadi-Sereshki, Yushan Huang, Nicholas J. Coupland, Nikolai Malykhin, Rawle Carter, Peter H. Silverstone, and Kathleen Hegadoren
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Adult ,Male ,Adolescent ,Poison control ,Hippocampus ,Hippocampal formation ,Amygdala ,Temporal lobe ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Adverse Childhood Experiences ,Humans ,Medicine ,Pharmacology (medical) ,Biological Psychiatry ,Depressive Disorder, Major ,business.industry ,Dentate gyrus ,Subiculum ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,030227 psychiatry ,Psychiatry and Mental health ,medicine.anatomical_structure ,Adult Survivors of Child Adverse Events ,nervous system ,Major depressive disorder ,Female ,business ,030217 neurology & neurosurgery ,Research Paper ,Clinical psychology - Abstract
Background Reductions in total hippocampus volume have frequently been reported in MRI studies in major depressive disorder (MDD), but reports of differences in total amygdala volume have been inconsistent. Childhood maltreatment is an important risk factor for MDD in adulthood and may affect the volume of the hippocampus and amygdala. In the present study, we examined associations between the volumes of the amygdala subnuclei and hippocampal subfields and history of childhood maltreatment in participants with MDD. Methods We recruited 35 patients who met the DSM-IV criteria for MDD and 35 healthy controls. We acquired MRI data sets on a 4.7 T Varian Inova scanner. We manually delineated the amygdala subnuclei (lateral, basal and accessory basal nuclei, and the cortical and centromedial groups) and hippocampal subfields (cornu ammonis, subiculum and dentate gyrus) using reliable volumetric methods. We assessed childhood maltreatment using the Childhood Trauma Questionnaire in participants with MDD. Results In participants with MDD, a history of childhood maltreatment had significant negative associations with volume in the right amygdala, anterior hippocampus and total cornu ammonis subfield bilaterally. For volumes of the amygdala subnuclei, such effects were limited to the basal, accessory basal and cortical subnuclei in the right hemisphere, but they did not survive correction for multiple comparisons. We did not find significant effects of MDD or antidepressant treatment on volumes of the amygdala subnuclei. Limitations Our study was a cross-sectional study. Conclusion Our results provide evidence of negative associations between history of childhood maltreatment and volumes of medial temporal lobe structures in participants with MDD. This may help to identify potential mechanisms by which maltreatment leads to clinical impacts.
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- 2021
23. Ventrolateral temporal lobectomy in normal dogs as a counterpart to human anterior temporal lobectomy: a preliminary study on the surgical procedure and complications
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Rikako Asada, Kazuyuki Uchida, Daisuke Hasegawa, James K. Chambers, Satoshi Mizuno, Yoshihiko Yu, and Yuji Hamamoto
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Drug Resistant Epilepsy ,medicine.medical_specialty ,medicine.medical_treatment ,Hippocampus ,Temporal muscle ,Temporal lobe ,Epilepsy ,surgical complication ,Dogs ,Atrophy ,temporal lobectomy ,Animals ,Humans ,Medicine ,Epilepsy surgery ,Dog Diseases ,Survival rate ,Anterior temporal lobectomy ,Full Paper ,General Veterinary ,business.industry ,Amygdalohippocampectomy ,Amygdala ,Anterior Temporal Lobectomy ,medicine.disease ,Surgery ,Treatment Outcome ,Epilepsy, Temporal Lobe ,dog ,epilepsy surgery ,business - Abstract
Anterior temporal lobectomy (ATL) is a surgical procedure for drug-resistant mesial temporal lobe epilepsy that is commonly performed in human medicine. The purpose of this study was to determine whether ATL-like surgery, i.e., removal of the amygdala and hippocampal head, is possible in dogs, and to investigate its safety and postoperative complications. Eight healthy beagles underwent ATL-like surgery and were observed for 3 months postoperatively. Samples from the surgically resected tissues and postmortem brain were evaluated pathologically. The surgical survival rate was 62.5%. The major postoperative complications were visual impairment, temporal muscle atrophy on the operative side, and a postoperative acute symptomatic seizure. Due to the anatomical differences between dogs and humans, the surgically resected area to approach the medial temporal structures in dogs was the ventrolateral part of the temporal lobe. Therefore, the ATL-like surgery described in this study was named "ventrolateral temporal lobectomy" (VTL). This study is the first report of temporal lobectomy including amygdalohippocampectomy in veterinary medicine and demonstrates its feasibility. Although it requires some degree of skill, VTL could be a treatment option for canine drug-resistant epilepsy and lesions in the mesial temporal lobe.
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- 2021
24. Cortico-cortical connectivity behind acoustic information transfer to mouse orbitofrontal cortex is sensitive to neuromodulation and displays local sensory gating: relevance in disorders with auditory hallucinations?
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Paolo Medini, Sebastian Sulis Sato, and Anushree Tripathi
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Male ,Psychosis ,Neuroactive steroid ,Hallucinations ,media_common.quotation_subject ,Dopamine ,Auditory area ,Prefrontal Cortex ,Amygdala ,behavioral disciplines and activities ,Mice ,Perception ,mental disorders ,medicine ,Animals ,Pharmacology (medical) ,Biological Psychiatry ,media_common ,Auditory Cortex ,Sensory gating ,Acoustics ,Sensory Gating ,medicine.disease ,Neuromodulation (medicine) ,Mice, Inbred C57BL ,Psychiatry and Mental health ,medicine.anatomical_structure ,nervous system ,Acoustic Stimulation ,Orbitofrontal cortex ,Female ,Psychology ,Neuroscience ,Neurosteroids ,psychological phenomena and processes ,Research Paper - Abstract
Background: Auditory hallucinations (which occur when the distinction between thoughts and perceptions is blurred) are common in psychotic disorders. The orbitofrontal cortex (OFC) may be implicated, because it receives multiple inputs, including sound and affective value via the amygdala, orchestrating complex emotional responses. We aimed to elucidate the circuit and neuromodulatory mechanisms that underlie the processing of emotionally salient auditory stimuli in the OFC — mechanisms that may be involved in auditory hallucinations. Methods: We identified the cortico-cortical connectivity conveying auditory information to the mouse OFC; its sensitivity to neuromodulators involved in psychosis and postpartum depression, such as dopamine and neurosteroids; and its sensitivity to sensory gating (defective in dysexecutive syndromes). Results: Retrograde tracers in OFC revealed input cells in all auditory cortices. Acoustic responses were abolished by pharmacological and chemogenetic inactivation of the above-identified pathway. Acoustic responses in the OFC were reduced by local dopaminergic agonists and neurosteroids. Noticeably, apomorphine action lasted longer in the OFC than in auditory areas, and its effect was modality-specific (augmentation for visual responses), whereas neurosteroid action was sex-specific. Finally, acoustic responses in the OFC reverberated to the auditory association cortex via feedback connections and displayed sensory gating, a phenomenon of local origin, given that it was not detectable in input auditory cortices. Limitations: Although our findings were for mice, connectivity and sensitivity to neuromodulation are conserved across mammals. Conclusion: The corticocortical loop from the auditory association cortex to the OFC is dramatically sensitive to dopamine and neurosteroids. This suggests a clinically testable circuit behind auditory hallucinations. The function of OFC input–output circuits can be studied in mice with targeted and clinically relevant mutations related to their response to emotionally salient sounds.
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- 2021
25. Borderline personality disorder classification based on brain network measures during emotion regulation
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Lourens J. Waldorp, Sascha B. Duken, Gregor Domes, Linda van Zutphen, Andreas Sprenger, Henk Cremers, Arnoud Arntz, RS: FPN CN 1, Vision, Klinische Psychologie (Psychologie, FMG), and Psychologische Methodenleer (Psychologie, FMG)
- Subjects
media_common.quotation_subject ,MODELS ,Dysfunctional family ,Disease cluster ,Phasic vs. tonic brain connectivity ,Amygdala ,Networks analysis ,03 medical and health sciences ,0302 clinical medicine ,HUBS ,Network measures ,Machine learning ,medicine ,Humans ,Personality ,Tonic (music) ,Pharmacology (medical) ,tonic brain connectivity ,Prefrontal cortex ,Borderline personality disorder ,Biological Psychiatry ,030304 developmental biology ,media_common ,Original Paper ,0303 health sciences ,PSYCHOPHYSIOLOGICAL INTERACTIONS ,Brain ,FUNCTIONAL CONNECTIVITY ,General Medicine ,Classification ,medicine.disease ,Magnetic Resonance Imaging ,Emotional Regulation ,Phasic vs ,AMYGDALA ,Psychiatry and Mental health ,medicine.anatomical_structure ,Sample size determination ,Case-Control Studies ,PSYCHIATRY ,Psychology ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Borderline Personality Disorder (BPD) is characterized by an increased emotional sensitivity and dysfunctional capacity to regulate emotions. While amygdala and prefrontal cortex interactions are regarded as the critical neural mechanisms underlying these problems, the empirical evidence hereof is inconsistent. In the current study, we aimed to systematically test different properties of brain connectivity and evaluate the predictive power to detect borderline personality disorder. Patients with borderline personality disorder (n = 51), cluster C personality disorder (n = 26) and non-patient controls (n = 44), performed an fMRI emotion regulation task. Brain network analyses focused on two properties of task-related connectivity: phasic refers to task-event dependent changes in connectivity, while tonic was defined as task-stable background connectivity. Three different network measures were estimated (strength, local efficiency, and participation coefficient) and entered as separate models in a nested cross-validated linear support vector machine classification analysis. Borderline personality disorder vs. non-patient controls classification showed a balanced accuracy of 55%, which was not significant under a permutation null-model, p = 0.23. Exploratory analyses did indicate that the tonic strength model was the highest performing model (balanced accuracy 62%), and the amygdala was one of the most important features. Despite being one of the largest data-sets in the field of BPD fMRI research, the sample size may have been limited for this type of classification analysis. The results and analytic procedures do provide starting points for future research, focusing on network measures of tonic connectivity, and potentially focusing on subgroups of BPD. Electronic supplementary material The online version of this article (10.1007/s00406-020-01201-3) contains supplementary material, which is available to authorized users.
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- 2020
26. Cerebellar-limbic neurocircuit is the novel biosignature of physio-cognitive decline syndrome
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Li Kuo Liu, Chih-Ping Chung, Liang Kung Chen, Ching Po Lin, Wei Ta Chen, Chih Chin Heather Hsu, Wei Ju Lee, Li Ning Peng, Kun Hsien Chou, and Pei Ning Wang
- Subjects
Male ,Aging ,medicine.medical_specialty ,Thalamus ,diffusion-weighted tractography ,brain volume ,frailty ,Audiology ,Amygdala ,Hippocampus ,Cohort Studies ,Cerebellum ,Neural Pathways ,medicine ,Limbic System ,Dementia ,magnetic resonance imaging ,Humans ,Cognitive Dysfunction ,Cognitive decline ,Gray Matter ,cognitive impairment ,Aged ,Muscle Weakness ,Hand Strength ,business.industry ,Brain ,Cognition ,Cell Biology ,Organ Size ,Middle Aged ,medicine.disease ,Temporal Lobe ,Walking Speed ,medicine.anatomical_structure ,Diffusion Magnetic Resonance Imaging ,Diffusion Tensor Imaging ,Case-Control Studies ,Brain size ,Female ,Occipital Lobe ,business ,Neuroanatomy ,Tractography ,Research Paper - Abstract
Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.
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- 2020
27. Modified Asano-Ohya-Khrennikov quantum-like model for decision-making process in a two-player game with nonlinear self- and cross-interaction terms of brain’s amygdala and prefrontal-cortex
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Husin Alatas, Hendradi Hardhienata, and Luluk Muthoharoh
- Subjects
0301 basic medicine ,Decision Making ,Biophysics ,Prefrontal Cortex ,Decision-making process ,01 natural sciences ,Models, Biological ,Two-player game ,03 medical and health sciences ,Asano-Ohya-Khrennikov quantum-like model ,0103 physical sciences ,Applied mathematics ,Humans ,Decision-making ,Prefrontal cortex ,Molecular Biology ,Quantum ,Mathematics ,Original Paper ,010304 chemical physics ,Contrast (statistics) ,Cell Biology ,Term (logic) ,Amygdala ,Atomic and Molecular Physics, and Optics ,Nonlinear system ,030104 developmental biology ,Nonlinear Dynamics ,Irrational number ,Quantum Theory - Abstract
In this report, we propose a modification on the Asano-Ohya-Khrennikov quantum-like decision-making process model of a two-player game by adding additional nonlinear terms to the related comparison step dynamical equation. The additions are in the form of a self-interaction and cross-interaction of the brain's amygdala and prefrontal cortex. We show that the cross-interaction significantly determines the final decision of a player, whether it becomes a rational or an irrational choice. In contrast, the nonlinear self-interaction term provides a feedback mechanism that speeds up the corresponding decision-making process. We also suggest the form of expectation values of the overall reaction rate coefficients of those nonlinear terms by making an analogy with the original model formulation.
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- 2020
28. Neonatal exposure to chlordecone alters female social behaviors and central estrogen alpha receptor expression in socially monogamous mandarin voles
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Lian Ting, Rong Wang, Huan Gao, Fadao Tai, Qi Yu, Wang Xiye, and Zhang Xudong
- Subjects
Paper ,Adrenergic receptor ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,Physiology ,010501 environmental sciences ,Biology ,Toxicology ,01 natural sciences ,Amygdala ,Social relation ,03 medical and health sciences ,Subcutaneous injection ,Stria terminalis ,0302 clinical medicine ,medicine.anatomical_structure ,Estrogen ,medicine ,Estrogen receptor alpha ,030217 neurology & neurosurgery ,0105 earth and related environmental sciences ,Social behavior - Abstract
Chlordecone (CD) is one of the common persistent organic pollutants in nature and has a profound impact on the environment and on public health. Accumulating evidence has demonstrated that neonatal exposure of CD influences adult physiology and behavior due to its estrogenic properties. Using socially monogamous mandarin voles as an experimental animal model, the present study aimed to evaluate the impact of neonatal exposure to CD on female social behaviors and central estrogen receptor alpha (ERα) expression in adulthood. After receiving a single subcutaneous injection with sesame seed oil (female control group), 17 beta-estradiol (E2 group), or CD group on postnatal Day 1, the social behaviors of adult animals and ERα expression in specific brain regions were assessed. The data indicated that CD or E2-treated female animals displayed increased affiliative behaviors and decreased aggressive behaviors with regard to the unfamiliar females in the social interaction test. In addition, CD or E2-treated female voles exhibited significant preferences to females over males in the sexual preference test. Moreover, CD-treated female animals exhibited higher levels of ERα expression in the bed nucleus of the stria terminalis, the central amygdala, the medial amygdala and the medial preoptic area compared with those of the control voles. The results suggested that neonatal exposure to CD may masculinize female social behaviors, possibly via CD-induced changes in the ERα expression of relevant brain regions.
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- 2020
29. Altered response to risky decisions and reward in patients with obsessive–compulsive disorder
- Author
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Nuno Sousa, Paulo Marques, José Miguel Soares, Julian Macoveanu, Ricardo Magalhães, Ana Coelho, Pedro Morgado, Pedro Moreira, Hartwig R. Siebner, and Universidade do Minho
- Subjects
Adult ,Male ,Obsessive-Compulsive Disorder ,Brain activity and meditation ,Medicina Básica [Ciências Médicas] ,Decision Making ,Precuneus ,Gyrus Cinguli ,behavioral disciplines and activities ,Lingual gyrus ,Young Adult ,03 medical and health sciences ,Risk-Taking ,0302 clinical medicine ,Reward ,Parietal Lobe ,Neural Pathways ,medicine ,Humans ,Cingulum (brain) ,Pharmacology (medical) ,Biological Psychiatry ,Anterior cingulate cortex ,030304 developmental biology ,0303 health sciences ,Science & Technology ,business.industry ,Functional Neuroimaging ,Brain ,Amygdala ,Magnetic Resonance Imaging ,3. Good health ,Psychiatry and Mental health ,medicine.anatomical_structure ,Ciências Médicas::Medicina Básica ,Rumination ,Anxiety ,Female ,Orbitofrontal cortex ,Occipital Lobe ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Research Paper ,Clinical psychology - Abstract
Background: Patients with obsessive–compulsive disorder (OCD) employ ritualistic behaviours to reduce or even neutralize the anxiety provoked by their obsessions. The presence of excessive rumination and indecision has motivated the view of OCD as a disorder of decision-making. Most studies have focused on the “cold,” cognitive aspects of decision-making. This study expands current understanding of OCD by characterizing the abnormalities associated with affective, or “hot” decision-making. Methods: We performed a functional MRI study in a sample of 34 patients with OCD and 33 sex-and age-matched healthy controls, during which participants made 2-choice gambles taking varying levels of risk. Results: During risky decisions, patients showed significantly reduced task-related activation in the posterior cingulum, lingual gyrus and anterior cingulate cortex. We identified significant group × risk interactions in the calcarine cortex, precuneus, amygdala and anterior cingulate cortex. During the outcome phase, patients with OCD showed stronger activation of the orbitofrontal cortex, anterior cingulate cortex and putamen in response to unexpected losses. Limitations: The group of patients not receiving medication was very small (n = 5), which precluded us from assessing the effect of medication on risk-taking behaviour in these patients. Conclusion: Obsessive–compulsive disorder is associated with abnormal brain activity patterns during risky decision-making in a set of brain regions that have been consistently implicated in the processing of reward prediction errors. Alterations in affective “hot” processes implicated in decision-making may contribute to increased indecisiveness and intolerance to uncertainty in patients with OCD., FCT fellow-ship grants (PhD-iHES program) with the references PDE/BDE/113601/2015 and PDE/BDE/113604/2015, respectively. P. Marques was funded by the Fundação Calouste Gulbenkian (Con-tract grant number P-139977, project “Better mental health during aging based on temporal prediction of individual brain aging trajec-tories [TEMPO]”). A. Coelho is supported by a scholarship from the project NORTE-08-5639-FSE-000041 (Norte Portugal Regional Opera-tional Programme, NORTE 2020; UMINHO/BD/51/2017). The pres-ent work was supported by SwitchBox-FP7-HEALTH-2010 grant 259772-2 and cofinanced by the Portuguese North Regional Opera-tional Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional De-velopment Fund (FEDER). H. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen, which is sponsored by the Lundbeck Foundation (grant no. R186-2015-2138).
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- 2020
30. Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex
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Thomas Senoner, Christian Siedentopf, Andrea Rubatscher, Florian Hintringer, Agne Adukauskaite, Noora Tuovinen, Wolfgang Dichtl, Axel Bauer, Elke R. Gizewski, Fabian Barbieri, and Ruth Steiger
- Subjects
medicine.medical_specialty ,Precuneus ,030204 cardiovascular system & hematology ,Insular cortex ,Amygdala ,03 medical and health sciences ,Limbic system ,0302 clinical medicine ,Internal medicine ,medicine ,Resting-state fMRI ,Anterior cingulate cortex ,Original Paper ,medicine.diagnostic_test ,Resting state fMRI ,Brain–heart axis ,business.industry ,General Medicine ,medicine.anatomical_structure ,Cardiology ,Takotsubo syndrome ,Cardiology and Cardiovascular Medicine ,business ,Functional magnetic resonance imaging ,Insula ,030217 neurology & neurosurgery - Abstract
BackgroundA brain–heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls.MethodsAnatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls.ResultsSignificantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p ConclusionIn the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.Graphic abstract
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- 2020
31. Neuroanatomical predictors of response to subcallosal cingulate deep brain stimulation for treatment-resistant depression
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Clement Hamani, Helen S. Mayberg, Peter Giacobbe, Andres M. Lozano, Sakina J. Rizvi, Tejas Sankar, Sidney H. Kennedy, Natasha Jawa, Stanley Xiangyu Li, and M. Mallar Chakravarty
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Adult ,Male ,medicine.medical_specialty ,Deep brain stimulation ,Deep Brain Stimulation ,medicine.medical_treatment ,Thalamus ,Grey matter ,Gyrus Cinguli ,Hippocampus ,Amygdala ,White matter ,Depressive Disorder, Treatment-Resistant ,03 medical and health sciences ,0302 clinical medicine ,Gyrus ,Internal medicine ,Outcome Assessment, Health Care ,0502 economics and business ,medicine ,Humans ,Pharmacology (medical) ,Gray Matter ,Biological Psychiatry ,Retrospective Studies ,business.industry ,05 social sciences ,Hamilton Rating Scale for Depression ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Psychiatry and Mental health ,medicine.anatomical_structure ,nervous system ,Cardiology ,Female ,050211 marketing ,business ,Treatment-resistant depression ,Biomarkers ,030217 neurology & neurosurgery ,Research Paper - Abstract
Background: Deep brain stimulation targeting the subcallosal cingulate gyrus (SCG DBS) improves the symptoms of treatment-resistant depression in some patients, but not in others. We hypothesized that there are pre-existing structural brain differences between responders and nonresponders to SCG DBS, detectable using structural MRI. Methods: We studied preoperative, T1-weighted MRI scans of 27 patients treated with SCG DBS from 2003 to 2011. Responders (n = 15) were patients with a > 50% improvement in Hamilton Rating Scale for Depression score following 12 months of SCG DBS. Preoperative subcallosal cingulate gyrus grey matter volume was obtained using manual segmentation by a trained observer blinded to patient identity. Volumes of hippocampus, thalamus, amygdala, whole-brain cortical grey matter and white matter volume were obtained using automated techniques. Results: Preoperative subcallosal cingulate gyrus, thalamic and amygdalar volumes were significantly larger in patients who went on to respond to SCG-DBS. Hippocampal volume did not differ between groups. Cortical grey matter volume was significantly smaller in responders, and cortical grey matter:white matter ratio distinguished between responders and nonresponders with high sensitivity and specificity. Limitations: Normalization by intracranial volume nullified some between-group differences in volumetric measures. Conclusion: There are structural brain differences between patients with treatment-resistant depression who respond to SCG DBS and those who do not. Specifically, the structural integrity of the subcallosal cingulate gyrus target region and its connected subcortical areas, and variations in cortical volume across the entire brain, appear to be important determinants of response. Structural MRI shows promise as a biomarker in deep brain stimulation for depression, and may play a role in refining patient selection for future trials.
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- 2020
32. Effect of Stereotaxic Surgery of the Third Ventricle on Growth Performance in Neonatal Chicks
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Yoshiyuki Ohta, Ryuzo Matsuda, Hikari Shimada, and Jun-ichi Shiraishi
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medicine.medical_specialty ,animal structures ,third ventricle ,040301 veterinary sciences ,Central nervous system ,Stimulation ,neonatal chick ,Biology ,Amygdala ,0403 veterinary science ,Arcuate nucleus ,Internal medicine ,energy metabolism ,medicine ,stereotaxic surgery ,growth performance ,Third ventricle ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,Full Papers ,040201 dairy & animal science ,Cannula ,Endocrinology ,medicine.anatomical_structure ,Hypothalamus ,Animal Science and Zoology ,Nucleus - Abstract
Feeding behavior and energy metabolism are precisely regulated by humoral and/or neural factors in the central nervous system. In particular, nuclei, such as the arcuate nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area located near the third ventricle of the hypothalamus are the centers of feeding and energy metabolism in various vertebrate species, including chickens. In this study, we evaluated the effects of cannulation of the third ventricle on chick growth and feeding behavior in the neonatal stage, to develop a method for local and chronic central nervous system-mediated energy metabolism. Referring to the chick brain atlas, a guide cannula was inserted into the third ventricle of the chick under anesthesia immediately after hatching using a stereotaxic instrument. The chicks that recovered from anesthesia were bred for 11 days under normal feeding management conditions, and then feed intake amount, body weight gain, and metabolic tissue weight were measured. The effects of direct stimulation of the third ventricle with 2-deoxy-D-glucose on the expression level of the immediate-early gene, cFOS, and feed intake in 5-day-old chicks were also evaluated. There were no differences in feed intake, body weight gain, and metabolic tissue weight between 11-day-old cannulated and control chicks. The expression of cFOS mRNA in the ventromedial hypothalamic nucleus was higher than that in the amygdala after the third ventricular administration of 2-deoxy-D-glucose. Additionally, direct third ventricular injection of 2-deoxy-D-glucose attenuated the feeding behavior of chicks for a while. Overall, we speculate that the technique is effective for local and/or chronic stimulation of the nucleus near the third ventricle of the chick hypothalamus, which is important for feed and energy metabolism regulation.
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- 2020
33. Amygdala and cognitive impairment in cerebral small vessel disease: structural, functional, and metabolic changes.
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Zhenyu Cheng, Wenying Nie, Junhong Leng, Linfeng Yang, Yuanyuan Wang, Xianglin Li, and Lingfei Guo
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CEREBRAL small vessel diseases ,AMYGDALOID body ,COGNITION disorders ,MAGNETIC resonance imaging - Abstract
Cerebral small vessel disease (CSVD) is a prevalent vascular disorder that has been consistently associated with vascular cognitive impairment (VCI). The diagnosis of CSVD continues to rely on magnetic resonance imaging (MRI). Epidemiological data indicate that the characteristic MRI features of CSVD, including white matter hyperintensity (WMH) and lacunar infarction, are very common among individuals over 40  years of age in community studies. This prevalence poses a significant burden on many low- and middle-income families. The amygdala plays a crucial role in integrating sensory and associative information to regulate emotional cognition. Although many previous studies have linked alterations in the amygdala to various diseases, such as depression, there has been little research on CSVD-associated alterations in the amygdala due to the complexity of CSVD. In this paper, we summarize the various imaging features of CSVD and discuss the correlation between amygdala changes and VCI. We also explore how new neuroimaging methods can assess amygdala changes early, laying a foundation for future comprehensive exploration of the pathogenesis of CSVD. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Disinhibition-assisted long-term potentiation in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons
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Alexei Morozov, Brendon Fusco, and Wataru Ito
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Paper ,Neuroscience (miscellaneous) ,Neural facilitation ,disinhibition ,Optogenetics ,Biology ,01 natural sciences ,Amygdala ,010309 optics ,03 medical and health sciences ,0302 clinical medicine ,0103 physical sciences ,medicine ,LTP induction ,Radiology, Nuclear Medicine and imaging ,long-term potentiation ,somatostatin interneurons ,Radiological and Ultrasound Technology ,musculoskeletal, neural, and ocular physiology ,Long-term potentiation ,amygdala ,Research Papers ,medicine.anatomical_structure ,nervous system ,Synaptic plasticity ,GABAergic ,Neuroscience ,030217 neurology & neurosurgery ,Basolateral amygdala - Abstract
Significance: Natural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High- and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression. This approach is effective in many brain areas but not in the basolateral amygdala (BLA) because the robust local GABAergic tone inside BLA restricts synaptic plasticity. Aim: We aimed at identifying the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC). Approach: Chemogenetic or optogenetic suppression of specific GABAergic neurons in BLA was combined with high-frequency stimulation of the BLA afferents as a method for LTP induction. Results: Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses, both ex vivo and in vivo. Conclusions: These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.
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- 2020
35. Blockade of corticotropin-releasing factor receptor 1 in the central amygdala prevents cocaine-seeking behaviour induced by orexin-A administered to the posterior paraventricular nucleus of the thalamus in male rats
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Alessandra Matzeu and Rémi Martin-Fardon
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Male ,Thalamus ,Nucleus accumbens ,Amygdala ,Receptors, Corticotropin-Releasing Hormone ,Orexin-A ,Cocaine-Related Disorders ,Cocaine ,medicine ,Animals ,Pharmacology (medical) ,Prefrontal cortex ,Biological Psychiatry ,Orexins ,business.industry ,Central nucleus of the amygdala ,Central Amygdaloid Nucleus ,Rats ,Psychiatry and Mental health ,Stria terminalis ,medicine.anatomical_structure ,business ,Neuroscience ,Basolateral amygdala ,Paraventricular Hypothalamic Nucleus ,Research Paper - Abstract
Background: Orexin-A (OrxA) administration in the posterior paraventricular nucleus of the thalamus (pPVT) reinstates extinguished cocaine-seeking behaviour following extended access to the drug (a model of dependence). The pPVT receives and integrates information associated with emotionally salient events and sends excitatory inputs to brain regions involved in the expression of emotional states, such as those driving cocaine-seeking behaviour (i.e., the nucleus accumbens, the central nucleus of the amygdala [CeA], the basolateral amygdala, the bed nucleus of the stria terminalis [BNST] and the prefrontal cortex). Methods: We monitored the activation pattern of these regions (measured by Fos) during cocaine-seeking induced by OrxA administered to the pPVT. The BNST and CeA emerged as being selectively activated. To test whether the functionality of these regions was pivotal during OrxA-induced cocaine-seeking behaviour, we transiently inactivated these regions concomitantly with OrxA administration to the pPVT. We then tested the participation of corticotropin-releasing factor receptors (CRF1) in the CeA during OrxA-induced cocaine-seeking using the CRF1 antagonist CP154526. Results: We observed selective activation of the CeA and BNST during cocaine-seeking induced by OrxA administered to the pPVT, but only transient inactivation of the CeA prevented cocaine-seeking behaviour. Administration of CP154526 to the CeA prevented OrxA-induced cocaine-seeking behaviour. Limitations: The use of only male rats could have been a limitation. Other limitations could have been the use of an indirect approach to test the hypothesis that administration of OrxA to the pPVT drives cocaine-seeking via CRF1 signalling in the CeA, and a lack of analysis of the participation of CeA subregions. Conclusion: Cocaine-seeking behaviour induced by OrxA administered to the pPVT is driven by activation of the CeA via CRF1 signalling.
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- 2021
36. Spared nerve injury differentially alters parabrachial monosynaptic excitatory inputs to molecularly specific neurons in distinct subregions of the central amygdala
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Patrick L. Sheets and Jun-Nan Li
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Male ,Corticotropin-releasing hormone ,Patch-Clamp Techniques ,Parabrachial nucleus ,Pain ,Mice, Transgenic ,Sensory system ,Optogenetics ,Biology ,Inhibitory postsynaptic potential ,Amygdala ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Slice preparation ,Peripheral Nerve Injuries ,030202 anesthesiology ,Neural Pathways ,medicine ,Animals ,Neurons ,Central nucleus of the amygdala ,Central Amygdaloid Nucleus ,digestive system diseases ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,nervous system ,Neurology ,Excitatory postsynaptic potential ,Neuralgia ,GABAergic ,Neurology (clinical) ,Somatostatin ,Neuroscience ,030217 neurology & neurosurgery ,Research Paper - Abstract
Using viral optogenetics in transgenic reporter mice, it was revealed that spared nerve injury model of neuropathic pain differentially alters synaptic efficacy of monosynaptic parabrachial inputs targeting distinct regions and neurons in the central amygdala., Dissecting the organization of circuit pathways involved in pain affect is pivotal for understanding behavior associated with noxious sensory inputs. The central nucleus of the amygdala (CeA) comprises distinct populations of inhibitory GABAergic neurons expressing a wide range of molecular markers. CeA circuits are associated with aversive learning and nociceptive responses. The CeA receives nociceptive signals directly from the parabrachial nucleus (PBn), contributing to the affective and emotional aspects of pain. Although the CeA has emerged as an important node in pain processing, key questions remain regarding the specific targeting of PBn inputs to different CeA subregions and cell types. We used a multifaceted approach involving transgenic reporter mice, viral vector-mediated optogenetics, and brain slice electrophysiology to delineate cell-type–specific functional organization of the PBn–CeA pathway. Whole-cell patch clamp recordings of molecularly defined CeA neurons while optogenetically driving long-range inputs originating from PBn revealed the direct monosynaptic excitatory inputs from PBn neurons to 3 major subdivisions of the CeA: laterocapsular (CeC), lateral (CeL), and medial (CeM). Direct monosynaptic excitatory inputs from PBn targeted both somatostatin-expressing (SOM+) and corticotropin-releasing hormone expressing (CRH+) neurons in the CeA. We find that monosynaptic PBn input is preferentially organized to molecularly specific neurons in distinct subdivisions of the CeA. The spared nerve injury model of neuropathic pain differentially altered PBn monosynaptic excitatory input to CeA neurons based on molecular identity and topographical location within the CeA. These results provide insight into the functional organization of affective pain pathways and how they are altered by chronic pain.
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- 2019
37. Deep sequencing of small non-coding RNA highlights brain-specific expression patterns and RNA cleavage
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Eduard Muráni, Siriluck Ponsuksili, Frieder Hadlich, Kevin Gley, Nares Trakooljul, Klaus Wimmers, and Fiete Haack
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Swine ,Hypothalamus ,Hippocampus ,Computational biology ,Biology ,Deep sequencing ,03 medical and health sciences ,0302 clinical medicine ,Memory ,Stress, Physiological ,Adrenal Glands ,Animals ,Hypoxia ,Molecular Biology ,030304 developmental biology ,RNA Cleavage ,0303 health sciences ,Genome ,High-Throughput Nucleotide Sequencing ,Molecular Sequence Annotation ,Fear ,Cell Biology ,Amygdala ,Non-coding RNA ,Adaptation, Physiological ,nervous system ,Gene Expression Regulation ,Organ Specificity ,030220 oncology & carcinogenesis ,Conditioning, Operant ,RNA, Small Untranslated ,Research Paper - Abstract
With the advance of high-throughput sequencing technology numerous new regulatory small RNAs have been identified, that broaden the variety of processing mechanisms and functions of non-coding RNA. Here we explore small non-coding RNA (sncRNA) expression in central parts of the physiological stress and anxiety response system. Therefore, we characterize the sncRNA profile of tissue samples from Amygdala, Hippocampus, Hypothalamus and Adrenal Gland, obtained from 20 pigs. Our analysis reveals that all tissues but Amygdala and Hippocampus possess distinct, tissue-specific expression pattern of miRNA that are associated with Hypoxia, stress responses as well as memory and fear conditioning. In particular, we observe marked differences in the expression profile of limbic tissues compared to those associated to the HPA/stress axis, with a surprisingly high aggregation of 3´-tRNA halves in Amygdala and Hippocampus. Since regulation of sncRNA and RNA cleavage plays a pivotal role in the central nervous system, our work provides seminal insights in the role/involvement of sncRNA in the transcriptional and post-transcriptional regulation of negative emotion, stress and coping behaviour in pigs, and mammals in general.
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- 2019
38. Novel objects elicit greater activation in the basolateral complex of the amygdala of wild rats compared with laboratory rats
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Kazuyuki D. Tanaka, Yasushi Kiyokawa, Yukari Takeuchi, Ryoko Koizumi, and Tsutomu Tanikawa
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Dorsum ,Male ,medicine.medical_specialty ,Brown rat ,neophobia ,040301 veterinary sciences ,Hypothalamus ,Animals, Wild ,Amygdala ,0403 veterinary science ,03 medical and health sciences ,Internal medicine ,medicine ,Avoidance Learning ,Animals ,defensive behavior ,Fluorescent Antibody Technique, Indirect ,030304 developmental biology ,0303 health sciences ,General Veterinary ,biology ,Full Paper ,new-object reaction ,Basolateral Nuclear Complex ,Neophobia ,Ethology ,04 agricultural and veterinary sciences ,biology.organism_classification ,medicine.disease ,neophilia ,Rats ,Stria terminalis ,medicine.anatomical_structure ,Endocrinology ,Home cage ,brown rat ,Nucleus ,Proto-Oncogene Proteins c-fos - Abstract
Wild animals tend to avoid novel objects that do not elicit clear avoidance behaviors in domesticated animals. We previously found that the basolateral complex of the amygdala (BLA) and dorsal bed nucleus of the stria terminalis (dBNST) were larger in trapped wild rats compared with laboratory rats. Based on these findings, we hypothesized that the BLA and/or dBNST would be differentially activated when wild and laboratory rats showed different avoidance behaviors towards novel objects. In this study, we placed novel objects at one end of the home cage. We measured the time spent in that half of the cage and expressed the data as a percentage of the time spent in that region with no object placement. We found that this percentage was lower in the wild rats compared with the laboratory rats. These behavioral differences were accompanied by increased Fos expression in the BLA, but not in the dBNST, of the wild rats. These results suggest that wild rats show greater BLA activation compared with laboratory rats in response to novel objects. We also found increased Fos expression in the paraventricular nucleus of the hypothalamus, ventral BNST, and ventromedial hypothalamus, but not in the central amygdala of wild rats. Taken together, our data represent new information regarding differences in behavioral and neural responses towards novel objects in wild vs. laboratory rats.
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- 2019
39. Long-term environmental enrichment affects microglial morphology in middle age mice
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Seemaab Ali, Nicholas J. Queen, Ryan K. Wilkins, Lei Cao, Xianglan Liu, Xiaokui Mo, and Ripal S. Patel
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medicine.medical_specialty ,Aging ,hippocampus ,Central nervous system ,Hypothalamus ,Hippocampus ,microglia ,Inflammation ,Biology ,Environment ,Amygdala ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,morphology ,medicine ,Animals ,Cell Shape ,Neuroinflammation ,030304 developmental biology ,0303 health sciences ,Environmental enrichment ,Microglia ,Cell Biology ,amygdala ,medicine.anatomical_structure ,Endocrinology ,environmental enrichment ,Cytokines ,Female ,medicine.symptom ,030217 neurology & neurosurgery ,Research Paper - Abstract
Aging is associated with increased central nervous system inflammation, in large part due to dysfunctional microglia. Environmental enrichment (EE) provides a model for studying the dynamics of lifestyle factors in the development of age-related neuroinflammation and microglial dysfunction. EE results in improvements in learning and memory, metabolism, and mental health in a variety of animal models. We recently reported that implementing EE in middle age promotes healthy aging. In the present study, we investigated whether EE influences microglial morphology, and whether EE is associated with changes in expression of microglial and neuroinflammatory markers. Inflammatory cytokines and MHC-II were reduced following 12-month EE in 10-month-old mice. Long-term EE for 7.5 months resulted in broad increases in Iba1 expression in hippocampus, hypothalamus, and amygdala detected by immunohistochemistry. Quantification of microglial morphology reveal both hypertrophy and ramification in these three brain regions, without increases in microglial cell density. These data indicate that long-term EE implemented in middle age results in a microglial state distinct from that of normal aging in standard laboratory housing, in specific brain regions, associated with reduced neuroinflammatory markers and improvement of systemic metabolism.
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- 2019
40. Fatty acid amide hydrolase binding is inversely correlated with amygdalar functional connectivity: a combined positron emission tomography and magnetic resonance imaging study in healthy individuals
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Sylvain Houle, Tina McCluskey, Isabelle Boileau, Stephen J. Kish, Duncan J. Westwood, Antonio P. Strafella, Duncan G.J. Green, Jinhee Kim, Nancy J. Lobaugh, Rachel F. Tyndale, Matthew N. Hill, and Junchao Tong
- Subjects
Adult ,Male ,Ventromedial prefrontal cortex ,Prefrontal Cortex ,Amygdala ,Amidohydrolases ,Fatty acid amide hydrolase ,medicine ,Humans ,Pharmacology (medical) ,Prefrontal cortex ,Biological Psychiatry ,Anterior cingulate cortex ,medicine.diagnostic_test ,Chemistry ,Magnetic resonance imaging ,Endocannabinoid system ,Magnetic Resonance Imaging ,Healthy Volunteers ,Psychiatry and Mental health ,medicine.anatomical_structure ,nervous system ,Positron emission tomography ,Positron-Emission Tomography ,Female ,Neuroscience ,psychological phenomena and processes ,Research Paper - Abstract
Background: Upregulation of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) has been linked to abnormal activity in frontoamygdalar circuits, a hallmark of posttraumatic stress disorder. We tested the hypothesis that FAAH levels in the amygdala were negatively correlated with functional connectivity between the amygdala and prefrontal cortex, subserving stress and affect control. Methods: Thirty-one healthy participants completed positron emission tomography (PET) imaging with the FAAH probe [C-11]CURB, and resting-state functional MRI scans. Participants were genotyped for the FAAH polymorphism rs324420, and trait neuroticism was assessed. We calculated amygdala functional connectivity using predetermined regions of interest (including the subgenual ventromedial prefrontal cortex [sgvmPFC] and the dorsal anterior cingulate cortex [dACC]) and a seed-to-voxel approach. We conducted correlation analyses on functional connectivity, with amygdala [C-11]CURB binding as a variable of interest. Results: The strength of amygdala functional connectivity with the sgvmPFC and dACC was negatively correlated with [C-11]CURB binding in the amygdala (sgvmPFC: r = −0.38, q = 0.04; dACC: r = –0.44; q = 0.03). Findings were partly replicated using the seed-to-voxel approach, which showed a cluster in the ventromedial prefrontal cortex, including voxels in the dACC but not the sgvmPFC (cluster-level, family-wise error rate corrected p < 0.05). Limitations: We did not replicate earlier findings of a relationship between an FAAH polymorphism (rs324420) and amygdala functional connectivity. Conclusion: Our data provide preliminary evidence that lower levels of FAAH in the amygdala relate to increased frontoamygdalar functional coupling. Our findings were consistent with the role of FAAH in regulating brain circuits that underlie fear and emotion processing in humans.
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- 2021
41. Resting-state functional connectivity of amygdala subregions across different symptom subtypes of obsessive-compulsive disorder patients.
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Kwon H, Ha M, Choi S, Park S, Jang M, Kim M, and Kwon JS
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- Humans, Male, Adult, Female, Young Adult, Neural Pathways physiopathology, Neural Pathways diagnostic imaging, Middle Aged, Brain Mapping methods, Rest physiology, Obsessive-Compulsive Disorder physiopathology, Obsessive-Compulsive Disorder diagnostic imaging, Amygdala physiopathology, Amygdala diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Aim: Obsessive-compulsive disorder (OCD) is a heterogeneous condition characterized by distinct symptom subtypes, each with varying pathophysiologies and treatment responses. Recent research has highlighted the role of the amygdala, a brain region that is central to emotion processing, in these variations. However, the role of amygdala subregions with distinct functions has not yet been fully elucidated. In this study, we aimed to clarify the biological mechanisms underlying OCD subtype heterogeneity by investigating the functional connectivity (FC) of amygdala subregions across distinct OCD symptom subtypes., Methods: Resting-state functional magnetic resonance images were obtained from 107 medication-free OCD patients and 110 healthy controls (HCs). Using centromedial, basolateral, and superficial subregions of the bilateral amygdala as seed regions, whole-brain FC was compared between OCD patients and HCs and among patients with different OCD symptom subtypes, which included contamination fear and washing, obsessive (i.e., harm due to injury, aggression, sexual, and religious), and compulsive (i.e., symmetry, ordering, counting, and checking) subtypes., Results: Compared to HCs, compulsive-type OCD patients exhibited hypoconnectivity between the left centromedial amygdala (CMA) and bilateral superior frontal gyri. Compared with patients with contamination fear and washing OCD subtypes, patients with compulsive-type OCD showed hypoconnectivity between the left CMA and left frontal cortex., Conclusions: CMA-frontal cortex hypoconnectivity may contribute to the compulsive presentation of OCD through impaired control of behavioral responses to negative emotions. Our findings underscored the potential significance of the distinct neural underpinnings of different OCD manifestations, which could pave the way for more targeted treatment strategies in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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42. A Randomized Controlled Trial of a Parenting Intervention During Infancy Alters Amygdala-Prefrontal Circuitry in Middle Childhood.
- Author
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Valadez EA, Tottenham N, Korom M, Tabachnick AR, Pine DS, and Dozier M
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- Male, Female, Humans, Child, Parents, Prefrontal Cortex diagnostic imaging, Psychopathology, Magnetic Resonance Imaging, Parenting psychology, Amygdala diagnostic imaging
- Abstract
Objective: Early adverse parenting predicts various negative outcomes, including psychopathology and altered development. Animal work suggests that adverse parenting might change amygdala-prefrontal cortex (PFC) circuitry, but work in humans remains correlational. The present study leveraged data from a randomized controlled trial examining the efficacy of an early parenting intervention targeting parental nurturance and sensitivity (Attachment and Biobehavioral Catch-up [ABC]) to test whether early parenting quality causally affects amygdala-PFC connectivity later in life., Method: Participants (N = 60, mean age = 10.0 years) included 41 high-risk children whose parents were referred by Child Protective Services and randomly assigned to receive either ABC (n = 21) or a control intervention (n = 20) during the children's infancy and a comparison sample of low-risk children (n = 19). Amygdala-PFC connectivity was assessed via functional magnetic resonance imaging while children viewed fearful and neutral faces., Results: Across facial expressions, ABC produced different changes than the control intervention in amygdala-PFC connectivity in response to faces. The ABC group also exhibited greater responses than the control intervention group to faces in areas classically associated with emotion regulation, including the orbitofrontal cortex and right insula. Mediation analysis suggested that the effect of ABC on PFC activation was mediated by the intervention's effect on amygdala-PFC connectivity., Conclusion: Results provide preliminary causal evidence for the effect of early parenting intervention on amygdala-PFC connectivity and on PFC responses to face viewing. Findings also highlight amygdala-PFC connectivity as a potential mediator of the effects of early parenting intervention on children's emotion regulation development., Clinical Trial Registration Information: Intervening Early With Neglected Children; https://clinicaltrials.gov/; NCT02093052., Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. All rights reserved.)
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- 2024
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43. Longitudinal effects of rTMS on neuroplasticity in chronic treatment-resistant depression
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Lieke Martens, Iris Dalhuisen, Eveline Ackermans, Jan Spijker, Peter F.A. Mulders, Philip van Eijndhoven, Alex de Bruijn, Joey Bartholomeus, and Indira Tendolkar
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Male ,medicine.medical_treatment ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Medizin ,Hippocampus ,Hippocampal formation ,Paralimbic cortex ,Experimental Psychopathology and Treatment ,Depressive Disorder, Treatment-Resistant ,0302 clinical medicine ,Dorsolateral Prefrontal Cortex ,rTMS ,Pharmacology (medical) ,Neuronal Plasticity ,Depression ,220 Statistical Imaging Neuroscience ,General Medicine ,Middle Aged ,Amygdala ,Transcranial Magnetic Stimulation ,Psychiatry and Mental health ,medicine.anatomical_structure ,Treatment Outcome ,Cingulate gyrus ,Cardiology ,Major depressive disorder ,Female ,psychological phenomena and processes ,medicine.medical_specialty ,Cortical thickness ,03 medical and health sciences ,Internal medicine ,Neuroplasticity ,medicine ,Humans ,Biological Psychiatry ,Depressive Disorder, Major ,Original Paper ,business.industry ,medicine.disease ,030227 psychiatry ,Transcranial magnetic stimulation ,nervous system ,business ,Treatment-resistant depression ,170 000 Motivational & Cognitive Control ,030217 neurology & neurosurgery - Abstract
Major depressive disorder (MDD) is amongst the most prevalent of psychiatric disorders. Unfortunately, a third of patients will not respond to conventional treatments and suffer from treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) has been proven effective in treating TRD. The research suggests that rTMS acts via neuroplastic effects on the brain, which can be measured by changes in hippocampal and amygdala volume as well as cortical thickness. This sham-controlled study investigates longitudinal effects of rTMS on the volumes of the hippocampus and amygdala and cortical thickness in patients with chronic TRD. 31 patients received 20 sessions of high-frequency rTMS (N = 15) or sham treatment (N = 16) over the left dorsolateral prefrontal cortex during 4 consecutive weeks. Using structural magnetic resonance imaging, we investigated longitudinal treatment effects on hippocampus and amygdala volume as well as thickness of the paralimbic cortex. We found no clinical differences between the active and sham rTMS group. Longitudinal changes in hippocampal and amygdala volume did not differ significantly, although males showed a significant decrease in left amygdala volume, irrespective of treatment group. Changes in cortical thickness of the paralimbic cortex differed significantly between the active and sham groups. Most notably, the increase in cortical thickness of the isthmus of the left cingulate gyrus was greater in the active as compared to the sham rTMS group. Our data suggest that rTMS can induce neuroplastic changes, particularly in cortical thickness, independent of treatment response. We also found longitudinal changes in amygdala volume in males. For clinical effects to follow these neuroplastic effects, more intensive rTMS treatment might be needed in chronically depressed patients. Trial registration number: ISRCTN 15535800, registered on 29-06-2017. Electronic supplementary material The online version of this article (10.1007/s00406-020-01135-w) contains supplementary material, which is available to authorized users.
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- 2021
44. Dopaminergic and noradrenergic modulation of stress-induced alterations in brain activation associated with goal-directed behaviour
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Bart Hartogsveld, Tom Smeets, Dennis Hernaus, Conny W.E.M. Quaedflieg, Peter van Ruitenbeek, Medical and Clinical Psychology, Section Psychopharmacology, RS: FPN NPPP II, RS: FPN NPPP I, Section Neuropsychology, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Section Forensic Psychology, RS: FPN CPS IV, Section Clinical Psychology, and RS: FPN CPS III
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Male ,Hydrocortisone ,Dopamine ,goal-directed behaviour ,Norepinephrine ,stress ,INSTRUMENTAL BEHAVIOR ,Pharmacology (medical) ,Cerebral Cortex ,Neurotransmitter Agents ,neuroimaging ,Chemistry ,MEDIAL PREFRONTAL CORTEX ,Dopaminergic ,Putamen ,Amygdala ,Original Papers ,Magnetic Resonance Imaging ,Ventral tegmental area ,Psychiatry and Mental health ,medicine.anatomical_structure ,LOCUS-COERULEUS ,Female ,Goals ,medicine.drug ,Brain activation ,Adult ,Adolescent ,INDUCED INCREASE ,PSYCHOSOCIAL STRESS ,Memory systems ,DRUG-ADDICTION ,Young Adult ,POSITRON-EMISSION-TOMOGRAPHY ,Reward ,medicine ,Humans ,Acute stress ,Pharmacology ,Stress induced ,Association Learning ,VENTRAL TEGMENTAL AREA ,Methylphenidate ,Locus coeruleus ,Conditioning, Operant ,MEMORY-SYSTEMS ,Neuroscience ,Stress, Psychological ,INDUCED RELAPSE - Abstract
Background: Acute stress is thought to reduce goal-directed behaviour, an effect purportedly associated with stress-induced release of catecholamines. In contrast, experimentally increased systemic catecholamine levels have been shown to increase goal-directed behaviour. Whether experimentally increased catecholamine function can modulate stress-induced reductions in goal-directed behaviour and its neural substrates, is currently unknown. Aim: To assess whether and how experimentally induced increases in dopamine and noradrenaline contribute to the acute stress effects on goal-directed behaviour and associated brain activation. Methods: One hundred participants underwent a stress induction protocol (Maastricht acute stress test; MAST) or a control procedure and received methylphenidate (MPH) (40 mg, oral) or placebo according to a 2 × 2 between-subjects design. In a well-established instrumental learning paradigm, participants learnt stimulus–response–outcome associations, after which rewards were selectively devalued. Participants’ brain activation and associated goal-directed behaviour were assessed in a magnetic resonance imaging scanner at peak cortisol/MPH concentrations. Results: The MAST and MPH increased physiological measures of stress (salivary cortisol and blood pressure), but only MAST increased subjective measures of stress. MPH modulated stress effects on activation of brain areas associated with goal-directed behaviour, including insula, putamen, amygdala, medial prefrontal cortex, frontal pole and orbitofrontal cortex. However, MPH did not modulate the tendency of stress to induce a reduction in goal-directed behaviour. Conclusion: Our neuroimaging data suggest that MPH-induced increases in dopamine and noradrenaline reverse stress-induced changes in key brain regions associated with goal-directed behaviour, while behavioural effects were absent. These effects may be relevant for preventing stress-induced maladaptive behaviour like in addiction or binge eating disorder.
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- 2021
45. Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial
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Olusola Ajilore, Joseph Wielgosz, Patrick Stetz, Philip W. Lavori, Joshua M. Smyth, Leanne M. Williams, Lan Xiao, Jun Ma, Nan Lv, Janine M. Simmons, Andrea N. Goldstein-Piekarski, Trisha Suppes, Megan A. Lewis, Elizabeth M. Venditti, Lisa G. Rosas, Mark B Snowden, Carlos Alexander Grajales Correa, and Sarah E. Chang
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0301 basic medicine ,Adult ,Male ,Medicine (General) ,Mediation (statistics) ,medicine.medical_specialty ,Emotions ,Problem-solving ,Collaborative Care ,Insula ,Neuroimaging ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,03 medical and health sciences ,R5-920 ,0302 clinical medicine ,Physical medicine and rehabilitation ,Randomized controlled trial ,Functional neuroimaging ,law ,Behavior Therapy ,Intervention (counseling) ,Connectome ,Medicine ,Humans ,Obesity ,Anterior cingulate cortex ,Depression (differential diagnoses) ,Problem Solving ,Aged ,Cerebral Cortex ,business.industry ,Depression ,General Medicine ,Middle Aged ,Amygdala ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,Research Paper - Abstract
Background Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. Methods This study (‘ENGAGE’) was a pre-planned element of the randomized controlled trial, ‘RAINBOW’ (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy (‘PST’)). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. Findings PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. Interpretation The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. Funding US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368
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- 2020
46. A meeting of aliens: an exploration in trying to increase moments of perceptual overlap with a neuro-diverse client.
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Hart, Carolyn
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TREATMENT of autism , *AMYGDALOID body , *NEURODIVERSITY , *PSYCHOTHERAPIST attitudes , *ANXIETY , *HELP-seeking behavior , *COMMUNICATIVE disorders , *ATTENTION , *PATIENT-professional relations - Abstract
This paper explores the challenge of establishing a meaningful connection between a neurotypical therapist and a neurodiverse patient who inhabit different Umwelts, that is, perceptual worlds.1 It discusses how addressing anxiety is crucial in preventing communication difficulties from escalating for individuals with autism who may have heightened stress due to an overgrown amygdala. Embodied mirroring is introduced to focus on perceptions and reduce stress. Furthermore, the potential for epigenetic changes due to unaddressed anxiety is raised. The paper emphasises the importance of responding to individual differences in sensory and perceptual experiences to promote effective communication and positive outcomes in therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Structural equation modeling of the associations between amygdala activation, personality, and internalizing, externalizing symptoms of psychopathology
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Craig S. Neumann
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Materials science ,Structural equation modeling (SEM) ,Externalizing and internalizing psychopathology ,Cognitive Neuroscience ,media_common.quotation_subject ,Neurogenetics ,Affective neuroscience ,Amygdala ,050105 experimental psychology ,Structural equation modeling ,Developmental psychology ,03 medical and health sciences ,Behavioral Neuroscience ,Amygdala activation ,0302 clinical medicine ,medicine ,Personality ,0501 psychology and cognitive sciences ,Big Five personality traits ,Personality traits ,media_common ,Facial expression ,05 social sciences ,Psychiatry and Mental health ,medicine.anatomical_structure ,Five-factor model ,Neurology (clinical) ,Empirical Paper ,030217 neurology & neurosurgery ,Psychopathology - Abstract
There is an expanding literature on the theoretical and empirical connections between personality and psychopathology, and their shared neurobiological correlates. Recent cybernetic theories of personality and psychopathology, as well as affective neuroscience theory, provide grounding for understanding neurobiological–personality–psychopathology (NPP) associations. With the emergence of large sample datasets (e.g., Human Connectome Project) advanced quantitative modeling can be used to rigorously test dynamic statistical representations of NPP connections. Also, research suggests that these connections are influenced by sex, and large samples provide the opportunity to examine how NPP associations might be moderated by sex. The current study used a large sample from the Duke Neurogenetics Study (DNS) to examine how amygdala activation to facial expressions was linked with self-report of personality traits and clinical interviews of internalizing and externalizing symptoms of psychopathology. Structural equation modeling results revealed direct associations of amygdala activation with personality trait expression, as well as indirect associations (though personality) with symptoms of psychopathology. Moreover, the NPP links were moderated by sex. The current results are in line with research that identifies a broader role played by the amygdala in personality and provide potential insights for continued research in personality neuroscience and recent theories on the neurobiology of personality.
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- 2020
48. Posttraumatic stress symptomatology and abnormal neural responding during emotion regulation under cognitive demands: mediating effects of personality
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Seth G. Disner, Scott R. Sponheim, Michael Sun, Shmuel Lissek, Craig A. Marquardt, Nicholas D. Davenport, and Philip C. Burton
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050103 clinical psychology ,Materials science ,Traumatic brain injury ,Brain activity and meditation ,Cognitive Neuroscience ,media_common.quotation_subject ,Posttraumatic stress ,Amygdala ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,medicine ,Personality ,Novel Investigations of the Connection between Quantitative Personality-Psychopathology Models and Neuroscience ,0501 psychology and cognitive sciences ,Attention ,Cognitive skill ,media_common ,Veterans ,medicine.diagnostic_test ,MMPI-2-RF ,Emotion regulation ,05 social sciences ,fMRI ,Anhedonia ,Cognition ,medicine.disease ,Psychiatry and Mental health ,medicine.anatomical_structure ,Neurology (clinical) ,Empirical Paper ,medicine.symptom ,Functional magnetic resonance imaging ,030217 neurology & neurosurgery ,psychological phenomena and processes ,Clinical psychology - Abstract
Posttraumatic stress disorder (PTSD) is often complicated by the after-effects of mild traumatic brain injury (mTBI). The mixture of brain conditions results in abnormal affective and cognitive functioning, as well as maladaptive behavior. To better understand how brain activity explains cognitive and emotional processes in these conditions, we used an emotional N-back task and functional magnetic resonance imaging (fMRI) to study neural responses in US military veterans after deployments to Iraq and Afghanistan. Additionally, we sought to examine whether hierarchical dimensional models of maladaptive personality could account for the relationship between combat-related brain conditions and fMRI responses under cognitive and affective challenge. FMRI data, measures of PTSD symptomatology (PTSS), blast-induced mTBI (bmTBI) severity, and maladaptive personality (MMPI-2-RF) were gathered from 93 veterans. Brain regions central to emotion regulation were selected for analysis, and consisted of bilateral amygdala, bilateral dorsolateral prefrontal (dlPFC), and ventromedial prefrontal/subgenual anterior cingulate (vmPFC-sgACC). Cognitive load increased activity in dlPFC and reduced activity in emotional responding brain regions. However, individuals with greater PTSS showed blunted deactivations in bilateral amygdala and vmPFC-sgACC, and weaker responses in right dlPFC. Additionally, we found that elevated emotional/internalizing dysfunction (EID), specifically low positive emotionality (RC2), accounted for PTSS-related changes in bilateral amygdala under increased cognitive load. Findings suggest that PTSS might result in amygdala and vmPFC-sgACC activity resistant to moderation by cognitive demands, reflecting emotion dysregulation despite a need to marshal cognitive resources. Anhedonia may be an important target for interventions that improve the affective and cognitive functioning of individuals with PTSD.
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- 2020
49. Conclusions in Gryglewski et al may not be warranted
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Marco Chiesa
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business.industry ,Depression ,imaging ,Amygdala ,Hippocampus ,Psychiatry and Mental health ,Depressive Disorder, Treatment-Resistant ,nervous system ,Electroconvulsive therapy ,inpatient treatment ,Papers ,Medicine ,Humans ,business ,depressive disorders - Abstract
Background Electroconvulsive therapy (ECT) is the treatment of choice for severe mental illness including treatment-resistant depression (TRD). Increases in volume of the hippocampus and amygdala following ECT have consistently been reported. Aims To investigate neuroplastic changes after ECT in specific hippocampal subfields and amygdala nuclei using high-resolution structural magnetic resonance imaging (MRI) (trial registration: clinicaltrials.gov – NCT02379767). Method MRI scans were carried out in 14 patients (11 women, 46.9 years (s.d. = 8.1)) with unipolar TRD twice before and once after a series of right unilateral ECT in a pre–post study design. Volumes of subcortical structures, including subfields of the hippocampus and amygdala, and cortical thickness were extracted using FreeSurfer. The effect of ECT was tested using repeated-measures ANOVA. Correlations of imaging and clinical parameters were explored. Results Increases in volume of the right hippocampus by 139.4 mm3 (s.d. = 34.9), right amygdala by 82.3 mm3 (s.d. = 43.9) and right putamen by 73.9 mm3 (s.d. = 77.0) were observed. These changes were localised in the basal and lateral nuclei, and the corticoamygdaloid transition area of the amygdala, the hippocampal–amygdaloid transition area and the granule cell and molecular layer of the dentate gyrus. Cortical thickness increased in the temporal, parietal and insular cortices of the right hemisphere. Conclusions Following ECT structural changes were observed in hippocampal subfields and amygdala nuclei that are specifically implicated in the pathophysiology of depression and stress-related disorders and retain a high potential for neuroplasticity in adulthood. Declaration of interest S.K. has received grants/research support, consulting fees and/or honoraria within the past 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. R.L. received travel grants and/or conference speaker honoraria from Shire, AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH.
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- 2020
50. Anatomic alterations across amygdala subnuclei in medication-free patients with obsessive-compulsive disorder
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Lu Lu, Shi Tang, Xuan Bu, Xiaoxiao Hu, Bin Li, John A. Sweeney, Qiyong Gong, Xinyu Hu, Yanchun Yang, Lianqing Zhang, Hailong Li, Yingxue Gao, and Xiaoqi Huang
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Adult ,Male ,medicine.medical_specialty ,Obsessive-Compulsive Disorder ,Reduced amygdala volume ,Population ,Amygdala ,Gastroenterology ,Young Adult ,Text mining ,Obsessive compulsive ,Internal medicine ,Medicine ,Humans ,Pharmacology (medical) ,Fear conditioning ,education ,Biological Psychiatry ,education.field_of_study ,business.industry ,Basolateral Nuclear Complex ,Central nucleus of the amygdala ,Central Amygdaloid Nucleus ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,medicine.anatomical_structure ,Anxiety ,Female ,medicine.symptom ,business ,Research Paper - Abstract
BACKGROUND: The amygdala has been implicated in obsessive–compulsive disorder (OCD), a common, disabling illness. However, the regional distribution of anatomic alterations in this structure and their association with the symptoms of OCD remains to be established. METHODS: We collected high-resolution 3D T(1)-weighted images from 81 untreated patients with OCD and no lifetime history of comorbid psychotic, affective or anxiety disorders, and from 95 age- and sex-matched healthy controls. We extracted the volume of the central nucleus of the amygdala (CeA) and the basolateral complex of the amygdala (BLA) and compared them across groups using FreeSurfer 6.0. In exploratory analyses, we evaluated other subnuclei, including the cortical medial nuclei, the anterior amygdaloid area, and the corticoamygdaloid transition area. RESULTS: Patients with OCD had reduced amygdala volume bilaterally compared with healthy controls (left, p = 0.034; right, p = 0.002). Volume reductions were greater in the CeA (left: −11.9%, p = 0.002; right: −13.3%, p < 0.001) than in the BLA (left lateral nucleus: −3.3%, p = 0.029; right lateral nucleus: −3.9%, p = 0.018; right basal nucleus: −4.1%, p = 0.017; left accessory basal nucleus: −6.5%, p = 0.001; right accessory basal nucleus: −9.3%, p < 0.001). Volume reductions in the CeA were associated with illness duration. Exploratory analysis revealed smaller medial (left: −15.4%, p < 0.001, η(2) = 0.101) and cortical (left: −9.1%, p = 0.001, η(2) = 0.058; right: −15.4%, p < 0.001, η(2) = 0.175) nuclei in patients with OCD compared with healthy controls. LIMITATIONS: Although the strict exclusion criteria used in the study helped us to identify OCD-specific alterations, they may have limited generalizability to the broader OCD population. CONCLUSION: Our results provide a comprehensive anatomic profile of alterations in the amygdala sub-nuclei in untreated patients with OCD and highlight a distinctive pattern of volume reductions across subnuclei in OCD. Based on the functional properties of the amygdala subnuclei established from preclinical research, CeA impairment may contribute to behavioural inflexibility, and BLA disruption may be responsible for altered fear conditioning and the affective components of OCD.
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- 2020
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