scholarly journals A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin

2020 ◽  
Author(s):  
Juan Kou ◽  
Yingying Zhang ◽  
Feng Zhou ◽  
Cornelia Sindermann ◽  
Christian Montag ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Emotional Behavior ◽  
Resting State Functional Connectivity ◽  
Social Emotional ◽  
Dose Frequency ◽  
Double Blind ◽  
Anxious Arousal ◽  
Male Subjects ◽  
Treatment Sensitivity

Abstract Background. The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment it is unclear whether efficacy may be influenced by dose frequency or genotype. Methods. In a randomized, double blind, placebo-controlled pharmaco-fMRI trial (150 male subjects) we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24IU) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting state functional connectivity between the amygdala and prefrontal cortex. Results. A single dose of oxytocin reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting state functional connectivity were not influenced by either dose-frequency or receptor genotype. Conclusions. Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.

scholarly journals A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin

2020 ◽  
pp. 1-10
Author(s):  
Juan Kou ◽  
Yingying Zhang ◽  
Feng Zhou ◽  
Cornelia Sindermann ◽  
Christian Montag ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Emotional Behavior ◽  
Functional Magnetic Resonance ◽  
Resting State Functional Connectivity ◽  
Social Emotional ◽  
Dose Frequency ◽  
Double Blind ◽  
Male Subjects ◽  
Treatment Sensitivity

Abstract Background The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment, it is unclear whether efficacy may be influenced by dose frequency or genotype. Methods In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex. Results A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype. Conclusions Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.

scholarly journals Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia

2019 ◽  
Vol 237 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Grant McQueen ◽  
Aderlee Lay ◽  
John Lally ◽  
Anthony S. Gabay ◽  
Tracy Collier ◽  
...  
Keyword(s):  
Single Dose ◽  
Functional Connectivity ◽  
Resting State ◽  
Pharmacological Action ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Frontal Pole ◽  
Resting State Functional Connectivity ◽  
Placebo Condition ◽  
Double Blind

Abstract Rationale There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. Objectives The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). Methods In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. Results Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). Conclusions These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

scholarly journals Multivoxel Neural Reinforcement Changes Resting-State Functional Connectivity Within the Threat Regulation Network

2020 ◽  
Author(s):  
Vincent Taschereau-Dumouchel ◽  
Toshinori Chiba ◽  
Ai Koizumi ◽  
Mitsuo Kawato ◽  
Hakwan Lau
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Temporal Cortex ◽  
Physiological Reactivity ◽  
Resting State Functional Connectivity ◽  
Double Blind ◽  
Brain Responses ◽  
Regulation Network ◽  
Before And After ◽  
Ventral Temporal Cortex

AbstractUsing neural reinforcement, participants can be trained to pair a reward with the activation of specific multivoxel patterns in their brains. In a double-blind placebo-controlled experiment, we previously showed that this intervention can decrease the physiological reactivity associated with naturally feared animals. However, the mechanisms behind the effect remain incompletely understood and its usefulness for treatment remains unclear. If the intervention fundamentally changed the brain responses, we might expect to observe relatively stable changes in the functional connectivity within the threat regulation network. To evaluate this possibility, we conducted functional magnetic resonance imaging (fMRI) sessions while subjects were at rest, before and after neural reinforcement, and quantified the changes in resting-state functional connectivity accordingly. Our results indicate that neural reinforcement increased the connectivity of prefrontal regulatory regions with the amygdala and the ventral temporal cortex (where the visual representations of phobic targets are). Surprisingly, we found no evidence of Hebbian-like learning during neural reinforcement, contrary to what one may expect based on previous neurofeedback studies. These results suggest that multivoxel neural reinforcement, also known as decoded neurofeedback (DecNef), may operate via unique mechanisms, distinct from those involved in conventional neurofeedback.

scholarly journals Cognitive enhancement: Effects of methylphenidate, modafinil and caffeine on latent memory and resting state functional connectivity in healthy adults

2021 ◽  
Author(s):  
Maxi Becker ◽  
Dimitris Repantis ◽  
Martin Dresler ◽  
Simone Kuehn
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Medial Temporal Lobe ◽  
Large Scale ◽  
Cognitive Enhancement ◽  
Brain Regions ◽  
Controlled Study ◽  
Attention And Memory ◽  
Resting State Functional Connectivity ◽  
Double Blind

Stimulants like methylphenidate, modafinil and caffeine have repeatedly shown to enhance cognitive processes such as attention and memory. However, brain-functional mechanisms underlying such cognitive enhancing effects of stimulants are still poorly characterized. Here, we utilized behavioral and resting-state fMRI data from a double-blind randomized placebo-controlled study of methylphenidate, modafinil and caffeine in 48 healthy male adults. The results show that performance in different memory tasks is enhanced, and functional connectivity (FC) specifically between the fronto-parietal (FPN) and default mode (DMN) network is modulated by the stimulants in comparison to placebo. Decreased negative connectivity between right prefrontal and medial parietal but also between medial temporal lobe and visual brain regions predicted stimulant-induced latent memory enhancement. We discuss dopamine's role in attention and memory as well as its ability to modulate FC between large-scale neural networks (e.g. FPN and DMN) as a potential cognitive enhancement mechanism.

scholarly journals Intrinsic, dynamic and effective connectivity among large-scale brain networks modulated by oxytocin

2020 ◽  
Author(s):  
Xi Jiang ◽  
Xiaole Ma ◽  
Yayuan Geng ◽  
Zhiying Zhao ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Emotional Processing ◽  
Large Scale ◽  
Effective Connectivity ◽  
Brain Networks ◽  
Emotional Behavior ◽  
Dependent Manner ◽  
Social Emotional ◽  
Using Data

AbstractThe neuropeptide oxytocin is a key modulator of social-emotional behavior and its intranasal administration can influence the functional connectivity of brain networks involved in the control of attention, emotion and reward reported in humans. However, no studies have systematically investigated the effects oxytocin on dynamic or directional aspects of functional connectivity. The present study employed a novel computational framework to investigate these latter aspects in 15 oxytocin-sensitive regions using data from randomized placebo-controlled between-subject resting state functional MRI studies incorporating 200 healthy subjects. Results showed that oxytocin extensively modulated effective connectivity both between and within emotion, reward, salience and social cognition processing networks and their interactions with the default mode network, but had no effect on the frequency of dynamic changes. Top-down control over emotional processing regions such as the amygdala was particularly affected. Oxytocin effects were also sex-dependent, being more extensive in males. Overall, these findings suggest that modulatory effects of oxytocin on both within- and between-network interactions may underlie its functional influence on social-emotional behaviors, although in a sex-dependent manner. Furthermore, they demonstrate a useful approach to determining pharmacological influences on resting state effective connectivity and support oxytocin’s potential therapeutic use in psychiatric disorders.

Effects of seven-day diazepam administration on resting-state functional connectivity in healthy volunteers: a randomized, double-blind study

2014 ◽  
Vol 232 (12) ◽  
pp. 2139-2147 ◽  
Author(s):  
C. Patrick Pflanz ◽  
Abbie Pringle ◽  
Nicola Filippini ◽  
Matthew Warren ◽  
Julia Gottwald ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Healthy Volunteers ◽  
Resting State ◽  
Blind Study ◽  
Double Blind Study ◽  
Resting State Functional Connectivity ◽  
Double Blind

scholarly journals Resting-state functional connectivity differentiates anxious apprehension and anxious arousal

2016 ◽  
Vol 53 (10) ◽  
pp. 1451-1459 ◽  
Author(s):  
Erin N. Burdwood ◽  
Zachary P. Infantolino ◽  
Laura D. Crocker ◽  
Jeffrey M. Spielberg ◽  
Marie T. Banich ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Resting State Functional Connectivity ◽  
Anxious Arousal ◽  
Anxious Apprehension

scholarly journals Functional connectivity of the anterior and posterior hippocampus: differential effects of glucose in younger and older adults

2018 ◽  
Author(s):  
Riccarda Peters ◽  
David J. White ◽  
Brian R. Cornwell ◽  
Andrew Scholey
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Resting State ◽  
Cognitive Testing ◽  
Human Cognition ◽  
Glucose Regulation ◽  
Resting State Functional Connectivity ◽  
Double Blind ◽  
Navigation Task ◽  
Glucose Ingestion

Abstract:The hippocampus features structurally and functionally distinct anterior and posterior segments. Relatively few studies have examined how these change during aging or in response to pharmacological interventions. Alterations in hippocampal connectivity and changes in glucose regulation have each been associated with cognitive decline in aging. A distinct line of research suggests that administration of glucose can lead to a transient improvement in hippocampus-dependent memory.Here we probe age, glucose and human cognition with a special emphasis on resting state functional connectivity (rsFC) of the hippocampus along its longitudinal axis to the rest of the brain. Using a randomized, placebo-controlled, double-blind, crossover design thirty-two healthy adults (16 young and 16 older) ingested a drink containing 25g glucose or placebo across two counterbalanced sessions. They then underwent resting state functional magnetic resonance imaging and cognitive testing. There was a clear dissociation in the effects of glucose by age. In older participants rsFC between posterior hippocampus (pHPC) and medial prefrontal cortex (mPFC) increased after glucose ingestion, whereas in younger participants connectivity decreased. Magnitude change in rsFC from pHPC to mPFC was correlated with individual glucose regulation and gains in performance on a spatial navigation task. Our results demonstrate that glucose administration can attenuate cognitive performance deficits in older adults with impaired glucose regulation and suggest that increases in pHPC-mPFC rsFC are beneficial for navigation task performance in older participants. This study is the first to demonstrate the selective modulation of pHPC connectivity in the acute setting.

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