Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence

2021 ◽  
Vol 118 (43) ◽  
pp. e2106624118
Author(s):  
Ida Fredriksson ◽  
Pei-Jung Tsai ◽  
Aniruddha Shekara ◽  
Ying Duan ◽  
Sarah V. Applebey ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Orbitofrontal Cortex ◽  
Resting State ◽  
Dorsal Striatum ◽  
Negative Consequences ◽  
Palatable Food ◽  
Self Administration ◽  
Drug Seeking ◽  
Food Seeking ◽  
Electric Barrier

We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier–induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier–induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier–induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.

scholarly journals Effects of long-term cocaine self-administration on brain resting-state functional connectivity in nonhuman primates

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Stephen J. Kohut ◽  
Dionyssios Mintzopoulos ◽  
Brian D. Kangas ◽  
Hannah Shields ◽  
Kelly Brown ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Cognitive Processing ◽  
Resting State ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Resting State Functional Connectivity ◽  
Self Administration ◽  
Chronic Cocaine

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.

scholarly journals Limbic links to paranoia: increased resting-state functional connectivity between amygdala, hippocampus and orbitofrontal cortex in schizophrenia patients with paranoia

2021 ◽  
Author(s):  
Sebastian Walther ◽  
Stephanie Lefebvre ◽  
Frauke Conring ◽  
Nicole Gangl ◽  
Niluja Nadesalingam ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Functional Connectivity ◽  
Orbitofrontal Cortex ◽  
Resting State ◽  
Healthy Controls ◽  
Schizophrenia Spectrum Disorders ◽  
Resting State Functional Connectivity ◽  
Paranoid Ideation ◽  
Syndrome Scale ◽  
Mri Scans

AbstractParanoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.

scholarly journals Cortical and thalamic influences on striatal involvement in instructed, serial reversal learning; implications for the organisation of flexible behaviour.

2021 ◽  
Author(s):  
Brendan Williams ◽  
Anastasia Christakou
Keyword(s):  
Functional Connectivity ◽  
Cognitive Flexibility ◽  
Reversal Learning ◽  
Orbitofrontal Cortex ◽  
Dorsal Striatum ◽  
Response Strategy ◽  
Flexible Control ◽  
The Right ◽  
Serial Reversal

Cognitive flexibility is essential for enabling an individual to respond adaptively to changes in their environment. Evidence from human and animal research suggests that the control of cognitive flexibility is dependent on an array of neural architecture. Cortico-basal ganglia circuits have long been implicated in cognitive flexibility. In particular, the role of the striatum is pivotal, acting as an integrative hub for inputs from the prefrontal cortex and thalamus, and modulation by dopamine and acetylcholine. Striatal cholinergic modulation has been implicated in the flexible control of behaviour, driven by input from the centromedian-parafascicular nuclei of the thalamus. However, the role of this system in humans is not clearly defined as much of the current literature is based on animal work. Here, we aim to investigate the roles corticostriatal and thalamostriatal connectivity in serial reversal learning. Functional connectivity between the left centromedian-parafascicular nuclei and the associative dorsal striatum was significantly increased for negative feedback compared to positive feedback. Similar differences in functional connectivity were observed for the right lateral orbitofrontal cortex, but these were localised to when participants switched to using an alternate response strategy following reversal. These findings suggest that connectivity between the centromedian-parafascicular nuclei and the striatum may be used to generally identify potential changes in context based on negative outcomes, and the effect of this signal on striatal output may be influenced by connectivity between the lateral orbitofrontal cortex and the striatum.

scholarly journals Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration

2018 ◽  
Vol 56 (5) ◽  
pp. 3603-3615 ◽  
Author(s):  
Christopher A. Blackwood ◽  
Reece Hoerle ◽  
Michael Leary ◽  
Jennifer Schroeder ◽  
Martin O. Job ◽  
...  
Keyword(s):  
Dorsal Striatum ◽  
Self Administration ◽  
Drug Seeking

scholarly journals Context-induced relapse to drug seeking: a review

2008 ◽  
Vol 363 (1507) ◽  
pp. 3233-3243 ◽  
Author(s):  
Hans S Crombag ◽  
Jennifer M Bossert ◽  
Eisuke Koya ◽  
Yavin Shaham
Keyword(s):  
Basolateral Amygdala ◽  
Dorsal Hippocampus ◽  
Dorsal Striatum ◽  
Self Administration ◽  
Occasion Setting ◽  
Drug Seeking ◽  
Psychological Mechanisms ◽  
History Of ◽  
Study Context

In humans, exposure to environmental contexts previously associated with drug intake often provokes relapse to drug use, but the mechanisms mediating this relapse are unknown. Based on early studies by Bouton & Bolles on context-induced ‘renewal’ of learned behaviours, we developed a procedure to study context-induced relapse to drug seeking. In this procedure, rats are first trained to self-administer drug in one context. Next, drug-reinforced lever responding is extinguished in a different (non-drug) context. Subsequently, context-induced reinstatement of drug seeking is assessed by re-exposing rats to the drug-associated context. Using variations of this procedure, we and others reported reliable context-induced reinstatement in rats with a history of heroin, cocaine, heroin–cocaine combination, alcohol and nicotine self-administration. Here, we first discuss potential psychological mechanisms of context-induced reinstatement, including excitatory and inhibitory Pavlovian conditioning, and occasion setting. We then summarize results from pharmacological and neuroanatomical studies on the role of several neurotransmitter systems (dopamine, glutamate, serotonin and opioids) and brain areas (ventral tegmental area, accumbens shell, dorsal striatum, basolateral amygdala, prefrontal cortex, dorsal hippocampus and lateral hypothalamus) in context-induced reinstatement. We conclude by discussing the clinical implications of rat studies on context-induced reinstatement of drug seeking.

Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder

NeuroImage ◽  
2011 ◽  
Vol 56 (3) ◽  
pp. 881-889 ◽  
Author(s):  
Andreas Hahn ◽  
Patrycja Stein ◽  
Christian Windischberger ◽  
Andreas Weissenbacher ◽  
Christoph Spindelegger ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Functional Connectivity ◽  
Social Anxiety ◽  
Social Anxiety Disorder ◽  
Orbitofrontal Cortex ◽  
Resting State ◽  
Resting State Functional Connectivity

Remitted major depression is related to increased functional coupling between ventral striatum and cortical regions in resting state fMRI

2011 ◽  
Vol 26 (S2) ◽  
pp. 948-948 ◽  
Author(s):  
G. Pail ◽  
C. Scharinger ◽  
K. Kalcher ◽  
W. Huf ◽  
R. Boubela ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Orbitofrontal Cortex ◽  
Resting State ◽  
Ventral Striatum ◽  
Resting State Fmri ◽  
Anterior Cingulate ◽  
Functional Coupling ◽  
Healthy Controls ◽  
Full Remission ◽  
Cortical Regions

IntroductionDysfunction in the basal ganglia has been related to impaired reward processing and anhedonia, a core symptom of Major Depressive Disorder (MDD). In particular, the ventral striatum including the nucleus accumbens is increasingly implicated in the pathophysiology of MDD, but evidence for a specific role during episodes of full remission is lacking so far.ObjectivesTo investigate functional connectivity patterns of resting-state activity in patients in the remitted phase of MDD (rMDD).AimsTo determine whether rMDD is related to disruptions of functional coupling between the ventral striatum and cortical regions.MethodsForty-three remitted depressed patients and thirty-five healthy controls were recruited at Medical University of Vienna, Vienna, Austria, and performed a six minute resting-state fMRI scan. Seed time series were extracted from the preprocessed data using individual masks for ventral striatum and correlated with all nodes in a surface based analysis using FreeSurfer, AFNI and SUMA. The resulting correlation coefficients were then Fishertransformed, group results were determined by comparing group mean smoothed z-scores with a two-sample ttest.ResultsIncreased resting-state functional connectivity was revealed between ventral striatum (seed region) and anterior cingulate cortex as well as orbitofrontal cortex in the rMDD group compared to healthy controls.ConclusionsOur preliminary data is in accordance with the idea that increased functional coupling between the ventral striatum and two major emotion processing regions, the anterior cingulate cortex and the orbitofrontal cortex, may represent a neural mechanism contributing to the maintenance of full remission of MDD.

scholarly journals Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence

2021 ◽  
Author(s):  
Ida Fredriksson ◽  
Aniruddha Shekara ◽  
Sarah V. Applebey ◽  
Angelica Minier-Toribio ◽  
Lindsay Altidor ◽  
...  
Keyword(s):  
Rat Model ◽  
Female Rats ◽  
Sprague Dawley ◽  
Self Administration ◽  
Drug Seeking ◽  
Neuronal Ensembles ◽  
Ventral Subiculum ◽  
Activity Marker ◽  
Electric Barrier

AbstractWe recently developed a rat model of incubation of oxycodone craving where opioid seeking progressively increases after voluntary suppression of drug self-administration by adverse consequences of drug seeking. Here, we studied the role of ventral subiculum (vSub) neuronal ensembles in this incubation, using the activity marker Fos, muscimol-baclofen (GABAergic agonists) inactivation, and Daun02 chemogenetic inactivation.We trained Sprague-Dawley or Fos-lacZ transgenic male and female rats to self-administer oxycodone (0.1 mg/kg/infusion, 6-h/d) for 14 days. The rats were then exposed for 14 days to an electric barrier of increasing intensity (0.1 to 0.4 mA) near the drug-paired lever that caused voluntary abstinence or were exposed to 14 days of forced abstinence. We tested Sprague-Dawley rats for relapse to oxycodone seeking without shock and drug on abstinence day 15 and extracted their brains for Fos-immunohistochemistry, or tested them after vSub vehicle or muscimol-baclofen injections on abstinence days 1 and 15. We performed Daun02 inactivation of relapse-activated vSub Fos neurons in Fos-lacZ transgenic rats on abstinence day 15 and then tested them for relapse on abstinence day 18.Relapse after electric barrier-induced abstinence increased Fos expression in vSub. Muscimol-baclofen inactivation or Daun02 selective inactivation of vSub Fos-expressing neuronal ensembles decreased “incubated” oxycodone seeking after voluntary abstinence. Muscimol-baclofen vSub inactivation had no effect on non-incubated opioid seeking on abstinence day 1 or incubation after forced abstinence.Our results demonstrate a selective role of vSub neuronal ensembles in incubation of opioid craving after cessation of drug self-administration by adverse consequences of drug seeking.Significance statementHigh relapse rate is a cardinal feature of opioid addiction and a major impediment for successful treatment. In humans, abstinence is often self-imposed, and relapse typically involves a conflict situation between the desire to experience the drug’s rewarding effects and negative consequences of drug seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence. Here, we used the activity marker Fos, muscimol-baclofen (GABAergic agonists) inactivation, and Daun02 chemogenetic inactivation to demonstrate a selective role of vSub neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence, but not in incubation of opioid craving after forced abstinence or non-incubated opioid seeking during early abstinence.

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