Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder

2017 ◽  
Vol 47 (15) ◽  
pp. 2675-2688 ◽  
Author(s):  
L. Brinkmann ◽  
C. Buff ◽  
K. Feldker ◽  
S. V. Tupak ◽  
M. P. I. Becker ◽  
...  

BackgroundPanic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD.MethodsUsing functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations.ResultsPD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks.ConclusionsWe demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

2017 ◽  
Author(s):  
Rachael M. Tillman ◽  
Melissa D. Stockbridge ◽  
Brendon M. Nacewicz ◽  
Salvatore Torrisi ◽  
Andrew S. Fox ◽  
...  

ABSTRACTThe central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)—plays a key role in orchestrating states of fear and anxiety and is implicated in the development and maintenance of anxiety disorders, depression, and substance abuse. Although it is widely thought that these disorders reflect the coordinated actions of large-scale functional circuits in the brain, the architecture of the EAc functional network, and the degree to which the BST and the Ce show distinct patterns of intrinsic functional connectivity, remains incompletely understood. Here, we leveraged a combination of approaches to trace the connectivity of the BST and the Ce in 130 psychiatrically healthy, racially diverse, community-dwelling adults with enhanced power and precision. Multiband imaging, high-precision data registration techniques, and spatially unsmoothed data were used to maximize anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala (‘substantia innominata’), the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed significant coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed significantly stronger connectivity with prefrontal territories—including the vmPFC, anterior MCC and pregenual anterior cingulate cortex—as well as the thalamus, striatum, and the periaqueductal gray. The only regions showing stronger functional connectivity with the Ce were located in the anterior hippocampus and dorsal amygdala. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and highlight the value of several new approaches to image registration which may be particularly useful for researchers working with ‘de-identified’ neuroimaging data.GRAPHICAL ABSTRACTIntrinsic functional connectivity of bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce) in 130 psychiatrically healthy adults.HIGHLIGHTSBST and Ce implicated in normal and pathological fear and anxietyTraced the intrinsic functional connectivity of the BST and the Ce in 130 adultsMultiband imaging, high-precision registration, unsmoothed data, newly developed seedsBST and Ce show robust coupling with one another, hippocampus, insula, MCC, and vmPFCBST shows stronger coupling with prefrontal/cingulate territories and brainstem/PAG


NeuroImage ◽  
2018 ◽  
Vol 166 ◽  
pp. 110-116 ◽  
Author(s):  
Leonie Brinkmann ◽  
Christine Buff ◽  
Katharina Feldker ◽  
Paula Neumeister ◽  
Carina Y. Heitmann ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Stephen J. Kohut ◽  
Dionyssios Mintzopoulos ◽  
Brian D. Kangas ◽  
Hannah Shields ◽  
Kelly Brown ◽  
...  

AbstractLong-term cocaine use is associated with a variety of neural and behavioral deficits that impact daily function. This study was conducted to examine the effects of chronic cocaine self-administration on resting-state functional connectivity of the dorsal anterior cingulate (dACC) and putamen—two brain regions involved in cognitive function and motoric behavior—identified in a whole brain analysis. Six adult male squirrel monkeys self-administered cocaine (0.32 mg/kg/inj) over 140 sessions. Six additional monkeys that had not received any drug treatment for ~1.5 years served as drug-free controls. Resting-state fMRI imaging sessions at 9.4 Tesla were conducted under isoflurane anesthesia. Functional connectivity maps were derived using seed regions placed in the left dACC or putamen. Results show that cocaine maintained robust self-administration with an average total intake of 367 mg/kg (range: 299–424 mg/kg). In the cocaine group, functional connectivity between the dACC seed and regions primarily involved in motoric behavior was weaker, whereas connectivity between the dACC seed and areas implicated in reward and cognitive processing was stronger. In the putamen seed, weaker widespread connectivity was found between the putamen and other motor regions as well as with prefrontal areas that regulate higher-order executive function; stronger connectivity was found with reward-related regions. dACC connectivity was associated with total cocaine intake. These data indicate that functional connectivity between regions involved in motor, reward, and cognitive processing differed between subjects with recent histories of cocaine self-administration and controls; in dACC, connectivity appears to be related to cumulative cocaine dosage during chronic exposure.


2019 ◽  
Vol 38 (03) ◽  
pp. 175-182 ◽  
Author(s):  
Ledismar José da Silva ◽  
Tâmara Husein Naciff ◽  
Maria Flávia Vaz de Oliveira

AbstractAnorexia nervosa is a psychiatric disorder characterized by distortions of body size, weight, and shape perception, as well as by food restriction and/or binge and purging behaviors. It mostly affects young women and causes severe negative impacts on their physical, psychological, and social health. Recent studies have analyzed deep brain stimulation (DBS), a neurosurgical procedure that involves electrode implantation in strategical brain areas, to obtain remission of the symptoms of anorexia nervosa. The results showed that the stimulation of areas associated to the neurocircuitry of anorexia nervosa, such as nucleus accumbens, anterior cingulate cortex, ventral striatum, and bed nucleus of the stria terminalis, provokes beneficial responses in terms of body mass index, quality of life, social functioning, and psychiatric comorbidities. Nevertheless, broader investigations are needed to endorse the clinical usage of DBS in the management of anorexia nervosa.


2020 ◽  
Vol 32 (6) ◽  
pp. 1026-1045 ◽  
Author(s):  
Dina R. Dajani ◽  
Paola Odriozola ◽  
Melanie Winters ◽  
Willa Voorhies ◽  
Selene Marcano ◽  
...  

Cognitive flexibility, the ability to appropriately adjust behavior in a changing environment, has been challenging to operationalize and validate in cognitive neuroscience studies. Here, we investigate neural activation and directed functional connectivity underlying cognitive flexibility using an fMRI-adapted version of the Flexible Item Selection Task (FIST) in adults ( n = 32, ages 19–46 years). The fMRI-adapted FIST was reliable, showed comparable performance to the computer-based version of the task, and produced robust activation in frontoparietal, anterior cingulate, insular, and subcortical regions. During flexibility trials, participants directly engaged the left inferior frontal junction, which influenced activity in other cortical and subcortical regions. The strength of intrinsic functional connectivity between select brain regions was related to individual differences in performance on the FIST, but there was also significant individual variability in functional network topography supporting cognitive flexibility. Taken together, these results suggest that the FIST is a valid measure of cognitive flexibility, which relies on computations within a broad corticosubcortical network driven by inferior frontal junction engagement.


2018 ◽  
Vol 3 (2) ◽  
pp. 59-64
Author(s):  
Xiping Liu ◽  
Yasutomo Imai ◽  
Yan Zhou ◽  
Sebastian Yu ◽  
Rupeng Li ◽  
...  

Functional connectivity magnetic resonance imaging (fcMRI), a specific form of MRI imaging, quantitatively assesses connectivity between brain regions that share functional properties. Functional connectivity magnetic resonance imaging has already provided unique insights into changes in the brain in patients with conditions such as depression and pain and symptoms that have been reported by patients with psoriasis and are known to impact quality of life. To identify the central neurological impact of psoriasiform inflammation of the skin, we applied fcMRI analysis to mice that had been topically treated with the Toll-like receptor agonist, imiquimod (IMQ) to induce psoriasiform dermatitis. Brain insula regions, due to their suggested role in stress, were chosen as seed regions for fcMRI analysis. Mouse ear and head skin developed psoriasiform epidermal thickening (up to 4-fold, P < .05) and dermal inflammation after 4 days of topical treatment with IMQ. After fcMRI analysis, IMQ-treated mice showed significantly increased insula fc with wide areas throughout the brain, including, but not limited to, the somatosensory cortex, anterior cingulate cortex, and caudate putamen ( P < .005). This reflects a potential central neurological impact of IMQ-induced psoriasis-like skin inflammation. These data indicate that fcMRI may be valuable tool to quantitatively assess the neurological impact of skin inflammation in patients with psoriasis.


2008 ◽  
Vol 32 (3) ◽  
pp. 283-298 ◽  
Author(s):  
Christopher M. Olsen ◽  
Yong Huang ◽  
Shirlean Goodwin ◽  
Daniel C. Ciobanu ◽  
Lu Lu ◽  
...  

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicole Steinhardt ◽  
Ramana Vishnubhotla ◽  
Yi Zhao ◽  
David M. Haas ◽  
Gregory M. Sokol ◽  
...  

Purpose: Infants of mothers with opioid and substance use can present with postnatal withdrawal symptoms and are at risk of poor neurodevelopmental outcomes in later childhood. Identifying methods to evaluate the consequences of substance exposure on the developing brain can help initiate proactive therapies to improve outcomes for opioid-exposed neonates. Additionally, early brain imaging in infancy has the potential to identify early brain developmental alterations that could prognosticate neurodevelopmental outcomes in these children. In this study, we aim to identify differences in global brain network connectivity in infants with prenatal opioid exposure compared to healthy control infants, using resting-state functional MRI performed at less than 2 months completed gestational age.   Materials and Methods: In this prospective, IRB-approved study, we recruited 20 infants with prenatal opioid exposure and 20 healthy, opioid naïve infants. Anatomic imaging and resting-state functional MRI were performed at less than 48 weeks corrected gestational age, and rs-fMRI images were co-registered to the UNC neonate brain template and 90 anatomic atlas-labelled regions. Covariate Assisted Principal (CAP) regression was performed to identify brain network functional connectivity that was significantly different among infants with prenatal opioid exposure compared to healthy neonates.   Results: Of the 5 significantly different CAP components identified, the most distinct component (CAP5, p= 3.86 x 10-6) spanned several brain regions, including the right inferior temporal gyrus, bilateral Hesch’s gyrus, left thalamus, left supramarginal gyrus, left inferior parietal lobule, left superior parietal gyrus, right anterior cingulate gyrus, right gyrus rectus, left supplementary motor area, and left pars triangularis. Functional connectivity in this network was lower in the infants with prenatal opioid exposure compared to non-opioid exposed infants.   Conclusion: This study demonstrates global network alterations in infants with prenatal opioid exposure compared to non-opioid exposed infants. Future studies should be aimed at identifying clinical significance of this altered connectivity.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261334
Author(s):  
Chizuko Hamada ◽  
Toshikazu Kawagoe ◽  
Masahiro Takamura ◽  
Atsushi Nagai ◽  
Shuhei Yamaguchi ◽  
...  

Apathy is defined as reduction of goal-directed behaviors and a common nuisance syndrome of neurodegenerative and psychiatric disease. The underlying mechanism of apathy implicates changes of the front-striatal circuit, but its precise alteration is unclear for apathy in healthy aged people. The aim of our study is to investigate how the frontal-striatal circuit is changed in elderly with apathy using resting-state functional MRI. Eighteen subjects with apathy (7 female, 63.7 ± 3.0 years) and eighteen subjects without apathy (10 female, 64.8 ± 3.0 years) who underwent neuropsychological assessment and MRI measurement were recruited. We compared functional connectivity with/within the striatum between the apathy and non-apathy groups. The seed-to-voxel group analysis for functional connectivity between the striatum and other brain regions showed that the connectivity was decreased between the ventral rostral putamen and the right dorsal anterior cingulate cortex/supplementary motor area in the apathy group compared to the non-apathy group while the connectivity was increased between the dorsal caudate and the left sensorimotor area. Moreover, the ROI-to-ROI analysis within the striatum indicated reduction of functional connectivity between the ventral regions and dorsal regions of the striatum in the apathy group. Our findings suggest that the changes in functional connectivity balance among different frontal-striatum circuits contribute to apathy in elderly.


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