scholarly journals Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit—a mechanism of relevance to resistant depression?

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1710 ◽  
Author(s):  
Jing J. Wong ◽  
Owen O’Daly ◽  
Mitul A. Mehta ◽  
Allan H. Young ◽  
James M. Stone

Background.Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions.Methods.Thirteen right-handed healthy male subjects underwent a 15 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration.Results.Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC activity became negatively correlated with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus.Discussion.Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.

2015 ◽  
Author(s):  
Jing J Wong ◽  
Owen O'Daly ◽  
Mitul A Mehta ◽  
James M Stone

Background: Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods: Thirteen right-handed healthy male subjects underwent a 15 minute resting state fMRI with an infusion of intravenous ketamine (target blood level=150ng/ml) starting at 5 minutes. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results: Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC coupling decreased with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion: Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.


2015 ◽  
Author(s):  
Jing J Wong ◽  
Owen O'Daly ◽  
Mitul A Mehta ◽  
James M Stone

Background: Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods: Thirteen right-handed healthy male subjects underwent a 15 minute resting state fMRI with an infusion of intravenous ketamine (target blood level=150ng/ml) starting at 5 minutes. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results: Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC coupling decreased with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion: Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.


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.


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.


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.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Irina S Samotaeva ◽  
Alla S Avedisova ◽  
Kseniya V Zakharova ◽  
Inna A Arkusha ◽  
Roman V Luzin ◽  
...  

Apathy is prevalent in older depressed patients and considered to be a predictor of increased dementia risk. Neuroimaging characteristics of late-life depression are being discussed. However, it is unclear whether apathetic (ApD) and nonapathetic depression (D) have different neuroimaging correlates. The objective of this study was to examine structural and functional bases of ApD by using morphometric and functional connectivity MRI analyses. We enrolled 45 consecutive patients with late-onset depression (85% female; mean age=66 (4) years, mean education=14 (2) years) and 22 age and gender-matched healthy elderly. Patients were divided into ApD (n=26) and D (n=19) groups based on Apathy Scale scores. All the participants underwent 1.5 T structural MRI and resting-state fMRI. Fazekas scale was used to quantify white matter hyperintensities. Demographic data, Hamilton Depression Rating Scale (HAMD), Apathy Scale, and MoCA scores for the three groups were compared. Association between apathy, depression and neuroimaging characteristics was assessed using regression analysis with demographic and cognitive variables included as covariates. ApD patients demonstrated nonsignificantly higher HAMD and Fazekas scores and lower MoCA scores compared to D patients. The latter group showed similar Fazekas and slightly lower MoCA scores vs healthy elderly. After controlling for covariates, apathy was significantly associated with volumes of nucleus caudatus and putamen on the right as well as functional connectivity between anterior cingulate and parahippocampal gyrus. Depression correlated with the volumes of the cerebral and cerebellum cortices as well as functional connectivity of salience resting state network. Our study demonstrated an association between volumes of basal ganglia, functional connectivity of anterior cingulate and apathy in late-onset depression.


Sign in / Sign up

Export Citation Format

Share Document