scholarly journals Acute and repeated intranasal oxytocin differentially modulate brain-wide functional connectivity

2019 ◽  
Author(s):  
Marco Pagani ◽  
Alessia De Felice ◽  
Caterina Montani ◽  
Alberto Galbusera ◽  
Francesco Papaleo ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Cerebral Blood Volume ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Social Impairment ◽  
Functional Coupling ◽  
Adult Mice ◽  
Term Administration

AbstractCentral release of the neuropeptide oxytocin (OXT) modulates neural substrates involved in socio-affective behavior. This property has prompted research into the use of intranasal OXT administration as an adjunctive therapy for brain conditions characterized by social impairment, such as autism spectrum disorders (ASD). However, the neural circuitry and brain-wide functional networks recruited by intranasal OXT administration remain elusive. Moreover, little is known of the neuroadaptive cascade triggered by long-term administration of this peptide at the network level. To address these questions, we applied fMRI-based circuit mapping in adult mice upon acute and repeated (seven-day) intranasal dosing of OXT. We report that acute and chronic OXT administration elicit comparable fMRI activity as assessed with cerebral blood volume mapping, but entail largely different patterns of brain-wide functional connectivity. Specifically, acute OXT administration focally boosted connectivity within key limbic components of the rodent social brain, whereas repeated dosing led to a prominent and widespread increase in functional connectivity, involving a strong coupling between the amygdala and extended cortical territories. Importantly, this connectional reconfiguration was accompanied by a paradoxical reduction in social interaction and communication in wild-type mice. Our results identify the network substrates engaged by exogenous OXT administration, and show that repeated OXT dosing leads to a substantial reconfiguration of brain-wide connectivity, entailing an aberrant functional coupling between cortico-limbic structures involved in socio-communicative and affective functions. Such divergent patterns of network connectivity might contribute to discrepant clinical findings involving acute or long-term OXT dosing in clinical populations.

scholarly journals Selective increase of functional network connectivity in Arc-positive neuronal engrams after long-term potentiation

2020 ◽  
Author(s):  
Yuheng Jiang ◽  
Antonius M.J. VanDongen
Keyword(s):  
Functional Connectivity ◽  
Hippocampal Neurons ◽  
Network Effects ◽  
Network Connectivity ◽  
Long Term Potentiation ◽  
Early Gene ◽  
Memory Traces ◽  
Term Potentiation ◽  
Memory Engram

ABSTRACTNew tools in optogenetics and molecular biology have culminated in recent studies which mark immediate-early gene (IEG)-expressing neurons as memory traces or engrams. Although the activity-dependent expression of IEGs has been successfully utilised to label memory traces, their roles in engram specification is incompletely understood. Outstanding questions remain as to whether expression of IEGs can interplay with network properties such as functional connectivity and also if neurons expressing different IEGs are functionally distinct. We investigated the expression of Arc and c-Fos, two commonly utilised IEGs in memory engram specification, in cultured hippocampal neurons. After pharmacological induction of long-term potentiation (LTP) in the network, we noted an emergent network property of refinement in functional connectivity between neurons, characterized by a global down-regulation of network connectivity, together with strengthening of specific connections. Subsequently, we show that Arc expression correlates with the effects of network refinement, with Arc-positive neurons being selectively strengthened. Arc positive neurons were also found to be located in closer physical proximity to each other in the network. While the expression pattern of IEGs c-Fos and Arc strongly overlaps, Arc was more selectively expressed than c-Fos. These IEGs also act together in coding information about connection strength pruning. These results demonstrate important links between IEG expression and network connectivity, which serve to bridge the gap between cellular correlates and network effects in learning and memory.

scholarly journals Characterization of postsurgical functional connectivity changes in temporal lobe epilepsy

2020 ◽  
Vol 133 (2) ◽  
pp. 392-402 ◽  
Author(s):  
Victoria L. Morgan ◽  
Baxter P. Rogers ◽  
Hernán F. J. González ◽  
Sarah E. Goodale ◽  
Dario J. Englot
Keyword(s):  
Functional Connectivity ◽  
Temporal Lobe ◽  
Network Connectivity ◽  
Temporal Lobectomy ◽  
Seizure Outcome ◽  
Seizure Recurrence ◽  
Female Age ◽  
Selective Amygdalohippocampectomy ◽  
The Brain

OBJECTIVESeizure outcome after mesial temporal lobe epilepsy (mTLE) surgery is complex and diverse, even across patients with homogeneous presurgical clinical profiles. The authors hypothesized that this is due in part to variations in network connectivity across the brain before and after surgery. Although presurgical network connectivity has been previously characterized in these patients, the objective of this study was to characterize presurgical to postsurgical functional network connectivity changes across the brain after mTLE surgery.METHODSTwenty patients with drug-refractory unilateral mTLE (5 left side, 10 female, age 39.3 ± 13.5 years) who underwent either selective amygdalohippocampectomy (n = 13) or temporal lobectomy (n = 7) were included in the study. Presurgical and postsurgical (36.6 ± 14.3 months after surgery) functional connectivity (FC) was measured with 3-T MRI and compared with findings in age-matched healthy controls (n = 44, 21 female, age 39.3 ± 14.3 years). Postsurgical connectivity changes were then related to seizure outcome, type of surgery, and presurgical disease parameters.RESULTSThe results demonstrated significant decreases of FC from control group values across the brain after surgery that were not present before surgery, including many contralateral hippocampal connections distal to the surgical site. Postsurgical impairment of contralateral precuneus to ipsilateral occipital connectivity was associated with seizure recurrence. Presurgical impairment of the contralateral precuneus to contralateral temporal lobe connectivity was associated with those who underwent selective amygdalohippocampectomy compared to those who had temporal lobectomy. Finally, changes in thalamic connectivity after surgery were linearly related to duration of epilepsy and frequency of consciousness-impairing seizures prior to surgery.CONCLUSIONSThe widespread contralateral hippocampal FC changes after surgery may be a reflection of an ongoing epileptogenic progression that has been altered by the surgery, rather than a direct result of the surgery itself. This network evolution may contribute to long-term seizure outcome. Therefore, the combination of presurgical network mapping with the understanding of the dynamic effects of surgery on the networks may ultimately be used to create predictors of the likelihood of long-term seizure recurrence in individual patients after mTLE surgery.

scholarly journals Reproducible functional connectivity alterations are associated with autism spectrum disorder

2018 ◽  
Author(s):  
Štefan Holiga ◽  
Joerg F. Hipp ◽  
Christopher H. Chatham ◽  
Pilar Garces ◽  
Will Spooren ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Large Scale ◽  
Clinical Symptoms ◽  
Brain Activity ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Replication Procedure ◽  
Medication Status

AbstractDespite the high clinical burden little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here we address these questions in the most comprehensive, large-scale effort to date comprising evaluation of four large ASD cohorts. We followed a strict exploration and replication procedure to identify core rs-fMRI functional connectivity (degree centrality) alterations associated with ASD as compared to typically developing (TD) controls (ASD: N=841, TD: N=984). We then tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status and clinical symptom severity. We find reproducible patterns of ASD-associated functional hyper- and hypo-connectivity with hypo-connectivity being primarily restricted to sensory-motor regions and hyper-connectivity hubs being predominately located in prefrontal and parietal cortices. We establish shifts in between-network connectivity from outside to within the identified regions as a key driver of these abnormalities. The magnitude of these alterations is linked to core ASD symptoms related to communication and social interaction and is not affected by age, sex or medication status. The identified brain functional alterations provide a reproducible pathophysiological phenotype underlying the diagnosis of ASD reconciling previous divergent findings. The large effect sizes in standardized cohorts and the link to clinical symptoms emphasize the importance of the identified imaging alterations as potential treatment and stratification biomarkers for ASD.

FURTHER EXPERIMENTAL AND CLINICAL FINDINGS DURING LONG-TERM ADMINISTRATION OF SYNTHETIC TRH

1972 ◽  
Vol 68 (3_Suppl) ◽  
pp. S4
Author(s):  
K. Retiene ◽  
H. Holz ◽  
A. Müller ◽  
R. Guthoff ◽  
H.-J. Ewers ◽  
...  
Keyword(s):  
Clinical Findings ◽  
Term Administration

Long-Term Administration of Intranasal Oxytocin Is a Safe and Promising Therapy for Early Adolescent Boys with Autism Spectrum Disorders

2013 ◽  
Vol 23 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Masaya Tachibana ◽  
Kuriko Kagitani-Shimono ◽  
Ikuko Mohri ◽  
Tomoka Yamamoto ◽  
Wakako Sanefuji ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Autism Spectrum ◽  
Early Adolescent ◽  
Adolescent Boys ◽  
Term Administration ◽  
Spectrum Disorders

scholarly journals A pilot study of serotonergic modulation after long‐term administration of oxytocin in autism spectrum disorder

2017 ◽  
Vol 10 (5) ◽  
pp. 821-828 ◽  
Author(s):  
Tetsu Hirosawa ◽  
Mitsuru Kikuchi ◽  
Yasuomi Ouchi ◽  
Tetsuya Takahashi ◽  
Yuko Yoshimura ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Pilot Study ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Term Administration ◽  
Serotonergic Modulation

scholarly journals Patients with autism spectrum disorders display reproducible functional connectivity alterations

2019 ◽  
Vol 11 (481) ◽  
pp. eaat9223 ◽  
Author(s):  
Štefan Holiga ◽  
Joerg F. Hipp ◽  
Christopher H. Chatham ◽  
Pilar Garces ◽  
Will Spooren ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Clinical Symptoms ◽  
Brain Activity ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Key Driver ◽  
Spectrum Disorders ◽  
Living Skills ◽  
Parietal Cortices ◽  
Medication Status

Despite the high clinical burden, little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here, we addressed these questions in four large ASD cohorts. Using rs-fMRI, we identified functional connectivity alterations associated with ASD. We tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status, and clinical symptom severity. Our results showed reproducible patterns of ASD-associated functional hyper- and hypoconnectivity. Hypoconnectivity was primarily restricted to sensory-motor regions, whereas hyperconnectivity hubs were predominately located in prefrontal and parietal cortices. Shifts in cortico-cortical between-network connectivity from outside to within the identified regions were shown to be a key driver of these abnormalities. This reproducible pathophysiological phenotype was partially associated with core ASD symptoms related to communication and daily living skills and was not affected by age, sex, or medication status. Although the large effect sizes in standardized cohorts are encouraging with respect to potential application as a treatment and for patient stratification, the moderate link to clinical symptoms and the large overlap with healthy controls currently limit the usability of identified alterations as diagnostic or efficacy readout.

scholarly journals Large-Scale Brain Functional Network Integration for Discrimination of Autism Using a 3-D Deep Learning Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Ming Yang ◽  
Menglin Cao ◽  
Yuhao Chen ◽  
Yanni Chen ◽  
Geng Fan ◽  
...  
Keyword(s):  
Deep Learning ◽  
Functional Connectivity ◽  
Large Scale ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Detection Accuracy ◽  
Learning Framework ◽  
Proposed Model ◽  
Deep Learning Model

GoalBrain functional networks (BFNs) constructed using resting-state functional magnetic resonance imaging (fMRI) have proven to be an effective way to understand aberrant functional connectivity in autism spectrum disorder (ASD) patients. It is still challenging to utilize these features as potential biomarkers for discrimination of ASD. The purpose of this work is to classify ASD and normal controls (NCs) using BFNs derived from rs-fMRI.MethodsA deep learning framework was proposed that integrated convolutional neural network (CNN) and channel-wise attention mechanism to model both intra- and inter-BFN associations simultaneously for ASD diagnosis. We investigate the effects of each BFN on performance and performed inter-network connectivity analysis between each pair of BFNs. We compared the performance of our CNN model with some state-of-the-art algorithms using functional connectivity features.ResultsWe collected 79 ASD patients and 105 NCs from the ABIDE-I dataset. The mean accuracy of our classification algorithm was 77.74% for classification of ASD versus NCs.ConclusionThe proposed model is able to integrate information from multiple BFNs to improve detection accuracy of ASD.SignificanceThese findings suggest that large-scale BFNs is promising to serve as reliable biomarkers for diagnosis of ASD.

scholarly journals Direct modulation of aberrant brain network connectivity through real-time NeuroFeedback

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Michal Ramot ◽  
Sara Kimmich ◽  
Javier Gonzalez-Castillo ◽  
Vinai Roopchansingh ◽  
Haroon Popal ◽  
...  
Keyword(s):  
Real Time ◽  
Resting State ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Brain Network ◽  
Control Group ◽  
Connectivity Patterns ◽  
Brain Network Connectivity ◽  
Resting State Connectivity

The existence of abnormal connectivity patterns between resting state networks in neuropsychiatric disorders, including Autism Spectrum Disorder (ASD), has been well established. Traditional treatment methods in ASD are limited, and do not address the aberrant network structure. Using real-time fMRI neurofeedback, we directly trained three brain nodes in participants with ASD, in which the aberrant connectivity has been shown to correlate with symptom severity. Desired network connectivity patterns were reinforced in real-time, without participants’ awareness of the training taking place. This training regimen produced large, significant long-term changes in correlations at the network level, and whole brain analysis revealed that the greatest changes were focused on the areas being trained. These changes were not found in the control group. Moreover, changes in ASD resting state connectivity following the training were correlated to changes in behavior, suggesting that neurofeedback can be used to directly alter complex, clinically relevant network connectivity patterns.

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