scholarly journals Changes in global brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

2017 ◽  
Author(s):  
Katrin H. Preller ◽  
Joshua B. Burt ◽  
Jie Lisa Ji ◽  
Charles Schleifer ◽  
Brendan Adkinson ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Resting State ◽  
Brain Connectivity ◽  
Subjective Effects ◽  
Critical Role ◽  
Resting State Fmri ◽  
Data Driven ◽  
Resting State Functional Connectivity ◽  
Double Blind ◽  
Global Brain

ABSTRACTLysergic acid diethylamide (LSD) is a psychedelic drug with predominantly agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, the specific receptor contributions to its neurobiological effects remain largely unknown. To address this knowledge gap, we conducted a double-blind, randomized, counterbalanced, cross-over study during which 24 healthy participants received either i) placebo+placebo, ii) placebo+LSD (100 μg po), or iii) ketanserin – a selective 5-HT2A receptor antagonist. Here we focus on resting-state fMRI, a measure of spontaneous neural fluctuations that can map functional brain connectivity. We collected resting-state data 75 and 300 minutes after LSD/placebo administration. We quantified resting-state functional connectivity via a fully data-driven global brain connectivity (GBC) method to comprehensively map LSD neuropharmacological effects. LSD administration caused widespread GBC alterations that followed a specific topography: LSD reduced connectivity in associative areas, but concurrently increased connectivity across sensory and somatomotor areas. The 5-HT2A receptor antagonist, ketanserin, fully blocked the subjective and neural LSD effects. We show that whole-brain data-driven spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans, which along with ketanserin effects, strongly implicates the 5-HT2A receptor in LSD’s neuropharmacology. Critically, the LSD-induced subjective effects were associated with somatomotor networks GBC changes. These data-driven neuropharmacological results pinpoint the critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics

scholarly journals Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katrin H Preller ◽  
Joshua B Burt ◽  
Jie Lisa Ji ◽  
Charles H Schleifer ◽  
Brendan D Adkinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Brain Connectivity ◽  
Critical Role ◽  
Resting State Functional Connectivity ◽  
Healthy Human ◽  
Double Blind ◽  
Trial Number ◽  
Rational Development ◽  
Human Participants

Background:Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown.Methods:We therefore conducted a double-blind, randomized, counterbalanced, cross-over studyduring which 24 healthy human participants received either (i) placebo+placebo, (ii) placebo+LSD (100 µg po), or (iii) Ketanserin, a selective 5-HT2A receptor antagonist,+LSD. We quantified resting-state functional connectivity via a data-driven global brain connectivity method and compared it to cortical gene expression maps.Results:LSD reduced associative, but concurrently increased sensory-somatomotor brain-wide and thalamic connectivity. Ketanserin fully blocked the subjective and neural LSD effects. Whole-brain spatial patterns of LSD effects matched 5-HT2A receptor cortical gene expression in humans.Conclusions:Together, these results strongly implicate the 5-HT2A receptor in LSD’s neuropharmacology. This study therefore pinpoints the critical role of 5-HT2A in LSD’s mechanism, which informs its neurobiology and guides rational development of psychedelic-based therapeutics.Funding:Funded by the Swiss National Science Foundation, the Swiss Neuromatrix Foundation, the Usona Institute, the NIH, the NIAA, the NARSAD Independent Investigator Grant, the Yale CTSA grant, and the Slovenian Research Agency.Clinical trial number:NCT02451072.

scholarly journals Modulation of Working Memory and Resting-State fMRI by tDCS of the Right Frontoparietal Network

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Monika Pupíková ◽  
Patrik Šimko ◽  
Martin Gajdoš ◽  
Irena Rektorová
Keyword(s):  
Working Memory ◽  
Resting State ◽  
Large Scale ◽  
Memory Task ◽  
Resting State Fmri ◽  
Resting State Functional Connectivity ◽  
Double Blind ◽  
Frontoparietal Network ◽  
Cognitive Speed ◽  
The Right

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.

scholarly journals Functional Alterations in Cerebellar Functional Connectivity in Anxiety Disorders

2020 ◽  
Author(s):  
Yoon Ji Lee ◽  
Xavier Guell ◽  
Nicholas A. Hubbard ◽  
Viviana Siless ◽  
Isabelle R. Frosch ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Anxiety Disorders ◽  
Resting State ◽  
Brain Connectivity ◽  
Resting State Fmri ◽  
Cortical Activation ◽  
Self Report ◽  
Resting State Functional Connectivity ◽  
Adolescent Anxiety ◽  
And Gender

AbstractAdolescents with anxiety disorders exhibit excessive emotional and somatic arousal. Neuroimaging studies have shown abnormal cerebral cortical activation and connectivity in this patient population. The specific role of cerebellar output circuitry, specifically the dentate nuclei (DN), in adolescent anxiety disorders remains largely unexplored. Resting-state functional connectivity analyses have parcellated the DN, the major output nuclei of the cerebellum, into three functional territories (FTs) that include default-mode, salience-motor, and visual networks. The objective of this study was to understand whether FTs of the DN are implicated in adolescent anxiety disorders. Forty-one adolescents (mean age 15.19 ± 0.82, 26 females) with one or more anxiety disorders and 55 age- and gender-matched healthy controls completed resting-state fMRI scans and a self-report survey on anxiety symptoms. Seed-to-voxel functional connectivity analyses were performed using the FTs from DN parcellation. Brain connectivity metrics were then correlated with State-Trait Anxiety Inventory (STAI) measures within each group. Adolescents with an anxiety disorder showed significant hyperconnectivity between salience-motor DN FT and cerebral cortical salience-motor regions compared to controls. Salience-motor FT connectivity with cerebral cortical sensorimotor regions was significantly correlated with STAI-trait scores in HC (R2 = 0.41). Here, we report DN functional connectivity differences in adolescents diagnosed with anxiety, as well as in HC with variable degrees of anxiety traits. These observations highlight the relevance of DN as a potential clinical and sub-clinical marker of anxiety.

scholarly journals Controlling for the effect of arterial-CO2 fluctuations in resting-state fMRI: Comparing end-tidal CO2 clamping and retroactive CO2 correction

2020 ◽  
Author(s):  
Ali M. Golestani ◽  
J. Jean Chen
Keyword(s):  
Resting State ◽  
Grey Matter ◽  
Brain Connectivity ◽  
Free Breathing ◽  
Resting State Fmri ◽  
Heart Beat ◽  
Physiological Noise ◽  
Intrinsic Connectivity ◽  
End Tidal ◽  
Global Brain

AbstractThe BOLD signal, as the basis of functional MRI, arises from both neuronal and vascular factors, with their respective contributions to resting state-fMRI still unknown. Among the factors contributing to “physiological noise”, dynamic arterial CO2 fluctuations constitutes the strongest and the most widespread modulator of the grey-matter rs-fMRI signal. Some important questions are: (1) if we were able to clamp arterial CO2 such that fluctuations are removed, what would happen to rs-fMRI measures? (2) falling short of that, is it possible to retroactively correct for CO2 effects with equivalent outcome? In this study 13 healthy subjects underwent two rs-fMRI acquisition: During the “clamped” run, end-tidal CO2 (PETCO2) is clamped to the average PETCO2 level of each participant, while during the “free-breathing” run, the PETCO2 level is passively monitored but not controlled. PETCO2 correction was applied to the free-breathing data by convolving PETCO2 with its BOLD response function, and then regressing out the result. We computed the BOLD resting-state fluctuation amplitude (RSFA), as well as seed-independent mean functional connectivity (FC) as the weighted global brain connectivity (wGBC). Furthermore, connectivity between conditions were compared using coupled intrinsic-connectivity distribution (ICD) method. We ensured that PETCO2 clamping did not significantly alter heart-beat and respiratory variation. We found that neither PETCO2 clamping nor correction produced significant change in RSFA and wGBC. In terms of the ICD, PETCO2 clamping and correction both reduced FC strength in the majority of grey matter regions, although the effect of PETCO2 correction is considerably smaller than the effect of PETCO2 clamping. Furthermore, while PETCO2 clamping reduced inter-subject variability in FC, PETCO2 correction increased the variability. Overall PETCO2 correction is not the equivalent of PETCO2 clamping, although it shifts FC values towards the same direction as clamping does.

scholarly journals Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals

2021 ◽  
Author(s):  
Drummond E-Wen McCulloch ◽  
Martin Korsbak Madsen ◽  
Dea Siggard Stenbæk ◽  
Sara Kristiansen ◽  
Brice Ozenne ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Clinical Symptoms ◽  
Brain Connectivity ◽  
Well Being ◽  
Resting State Fmri ◽  
Long Term Effects ◽  
Resting State Functional Connectivity ◽  
Positive Effects ◽  
Personality Changes

ABSTRACTBackgroundPsilocybin is a psychedelic drug that has shown lasting positive effects on clinical symptoms and self-reported well-being following a single dose. There has been little research into the long-term effects of psilocybin on brain connectivity in humans.AimsEvaluate changes in resting-state functional connectivity (RSFC) at one-week and three-months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures.MethodsParticipants received 0.2-0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state fMRI scans at baseline, one-week and three-months post-administration and [11C]Cimbi-36 PET scans at baseline and one-week. We examined changes in within-network, between-network and region-to-region RSFC. We explored associations between changes in RSFC and psilocybin-induced phenomenology as well as changes in psychological measures and neocortex serotonin 2A receptor binding.ResultsPsilocybin was well tolerated and produced positive changes in well-being. At one-week only, executive control network (ECN) RSFC was significantly decreased (Cohen’s d=-1.73, pFWE=0.010). We observed no other significant changes in RSFC at one-week or three-months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at one-week predicted increased mindfulness at three-months (r =-0.65).ConclusionsThese findings in a small cohort indicate that psilocybin affects ECN function within the psychedelic “afterglow” period. Our findings implicate ECN modulation as mediating psilocybin-induced, long-lasting increases in mindfulness. Although our findings implicate a neural pathway mediating lasting psilocybin effects, it is notable that changes in neuroimaging measures at three-months, when personality changes are observed, remain to be identified.

scholarly journals A Quantitative Data-Driven Analysis (QDA) Framework for Resting-state fMRI: a Study of the Impact of Adult Age

2021 ◽  
Author(s):  
Xia Li ◽  
Håkan Fischer ◽  
Amirhossein Manzouri ◽  
Kristoffer N.T. Månsson ◽  
Tie-Qiang Li
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Quantitative Data ◽  
Resting State Fmri ◽  
Data Driven ◽  
Fmri Data ◽  
Resting State Functional Connectivity ◽  
Sensorimotor Network ◽  
Adult Age ◽  
Connectivity Strength

AbstractPurposeThe objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC).MethodsWhole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index (CSI) and connectivity density index (CDI) utilizing the convolutions of the cross-correlation (CC) histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately.ResultsWith the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyrus (MFG), posterior cingulate cortex (PCC), right insula and inferior parietal lobule (IPL) of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: 1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; 2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; 3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age.ConclusionThe proposed QDA framework can produce threshold-free, voxel-wise analysis of R-fMRI data the RFC metrics. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in adult aging.HighlightsA quantitative data-driven analysis (QDA) framework was proposed to analysis resting-state fMRI data.Threshold-free resting-state functional connectivity (RFC) metrics were derived to assess brain changes with adult age.Separate assessment of the positive and negative correlations improve sensitivity of the RFC metrics.The posterior cingulate and right insula cortices are anti-correlated and tend to manifest declines in both the negative and positive connectivity strength with adult age.Negative connectivity strength enhances with adult age in sensorimotor network.

scholarly journals Resting-State Functional Connectivity of the Punishment Network Associated With Conformity

2020 ◽  
Vol 14 ◽  
Author(s):  
Yin Du ◽  
Yinan Wang ◽  
Mengxia Yu ◽  
Xue Tian ◽  
Jia Liu
Keyword(s):  
Individual Differences ◽  
Functional Connectivity ◽  
Resting State ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Brain Regions ◽  
Resting State Functional Connectivity ◽  
Three Phase ◽  
The Right ◽  
Global Brain

Fear of punishment prompts individuals to conform. However, why some people are more inclined than others to conform despite being unaware of any obvious punishment remains unclear, which means the dispositional determinants of individual differences in conformity propensity are poorly understood. Here, we explored whether such individual differences might be explained by individuals’ stable neural markers to potential punishment. To do this, we first defined the punishment network (PN) by combining all potential brain regions involved in punishment processing. We subsequently used a voxel-based global brain connectivity (GBC) method based on resting-state functional connectivity (FC) to characterize the hubs in the PN, which reflected an ongoing readiness state (i.e., sensitivity) for potential punishment. Then, we used the within-network connectivity (WNC) of each voxel in the PN of 264 participants to explain their tendency to conform by using a conformity scale. We found that a stronger WNC in the right thalamus, left insula, postcentral gyrus, and dACC was associated with a stronger tendency to conform. Furthermore, the FC among the four hubs seemed to form a three-phase ascending pathway, contributing to conformity propensity at every phase. Thus, our results suggest that task-independent spontaneous connectivity in the PN could predispose individuals to conform.

scholarly journals Impact of Binge Drinking During College on Resting State Functional Connectivity

2021 ◽  
Author(s):  
Tien T. Tong ◽  
Jatin G. Vaidya ◽  
John R. Kramer ◽  
Samuel Kuperman ◽  
Douglas R. Langbehn ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Binge Drinking ◽  
Resting State ◽  
Brain Connectivity ◽  
Network Connectivity ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Resting State Functional Connectivity ◽  
Functional Connection ◽  
Level Analysis

AbstractAimThe current study aimed to examine the longitudinal effects of standard binge drinking (4+/5+ drinks for females/males in 2 hours) and extreme binge drinking (8+/10+ drinks for females/males in 2 hours) on resting state functional connectivity.Method119 college students with distinct alcohol bingeing patterns (35 non-bingeing controls, 44 standard bingers, and 40 extreme bingers) were recruited to ensure variability in bingeing frequency. Resting state fMRI scans were obtained at time 1 when participants were college freshmen and sophomores and again approximately two years later. On four occasions during the 2-year period between scans, participants reported monthly standard and extreme binge drinking for the past 6 months. Association between bingeing and change in functional connectivity was studied using both network-level and edge-level analysis. Network connectivity was calculated by aggregating multiple edges (a functional connection between any two brain regions) affiliated with the same network. The network-level analysis used mixed-effects models to assess the association between standard/extreme binge drinking and change in network connectivity, focusing on canonical networks often implicated in substance misuse. On the other hand, the edge-level analysis tested the relationship between bingeing and change in whole-brain connectivity edges using connectome-based predictive modeling (CPM).ResultsFor network-level analysis, higher standard bingeing was associated with a decrease in connectivity between Default Mode Network-Ventral Attention Network (DMN-VAN) from time 1 to time 2, controlling for the initial binge groups at time 1, longitudinal network changes, in-scanner motion and other demographic covariates. For edge-level analysis, the CPM failed to identify a generalizable predictive model of cumulative standard/extreme bingeing from change in connectivity edges.ConclusionsOur findings suggest that binge drinking is associated with abnormality in networks implicated in attention allocation and self-focused processes, which, in turn, have been implicated in rumination, craving, and relapse. More extensive alterations in functional connectivity might be observed with heavier or longer binge drinking pattern.

Tracking whole-brain connectivity dynamics in the resting-state fMRI with post-facial paralysis synkinesis

2021 ◽  
Author(s):  
Zhen-Zhen Ma ◽  
Jia-Jia Wu ◽  
Xu-Yun Hua ◽  
Mou-Xiong Zheng ◽  
Xiang-Xin Xing ◽  
...  
Keyword(s):  
Facial Paralysis ◽  
Resting State ◽  
Brain Connectivity ◽  
Resting State Fmri ◽  
Whole Brain

Sensory Processing Sensitivity Predicts Individual Differences in Resting-State Functional Connectivity Associated with Depth of Processing

2021 ◽  
pp. 1-15
Author(s):  
Bianca P. Acevedo ◽  
Tyler Santander ◽  
Robert Marhenke ◽  
Arthur Aron ◽  
Elaine Aron
Keyword(s):  
Individual Differences ◽  
Cognitive Processing ◽  
Sensory Processing ◽  
Resting State ◽  
Brain Connectivity ◽  
Region Of Interest ◽  
Central Feature ◽  
Resting State Functional Connectivity ◽  
Depth Of Processing ◽  
Sensory Processing Sensitivity

<b><i>Background:</i></b> Sensory processing sensitivity (SPS) is a biologically based temperament trait associated with enhanced awareness and responsivity to environmental and social stimuli. Individuals with high SPS are more affected by their environments, which may result in overarousal, cognitive depletion, and fatigue. <b><i>Method:</i></b> We examined individual differences in resting-state (rs) brain connectivity (using functional MRI) as a function of SPS among a group of adults (<i>M</i> age = 66.13 ± 11.44 years) immediately after they completed a social affective “empathy” task. SPS was measured with the Highly Sensitive Person (HSP) Scale and correlated with rs brain connectivity. <b><i>Results:</i></b> Results showed enhanced rs brain connectivity within the ventral attention, dorsal attention, and limbic networks as a function of greater SPS. Region of interest analyses showed increased rs brain connectivity between the hippocampus and the precuneus (implicated in episodic memory); while weaker connectivity was shown between the amygdala and the periaqueductal gray (important for anxiety), and the hippocampus and insula (implicated in habitual cognitive processing). <b><i>Conclusions:</i></b> The present study showed that SPS is associated with rs brain connectivity implicated in attentional control, consolidation of memory, physiological homeostasis, and deliberative cognition. These results support theories proposing “depth of processing” as a central feature of SPS and highlight the neural processes underlying this cardinal feature of the trait.

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