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

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.

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

Journal of Psychopharmacology ◽

10.1177/02698811211026454 ◽

2021 ◽

pp. 026988112110264

Author(s):

Drummond E-Wen McCulloch ◽

Martin Korsbak Madsen ◽

Dea Siggaard Stenbæk ◽

Sara Kristiansen ◽

Brice Ozenne ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Clinical Symptoms ◽

Brain Connectivity ◽

Well Being ◽

Long Term Effects ◽

Resting State Functional Connectivity ◽

Positive Effects ◽

Personality Changes ◽

Psychedelic Drug

Background: Psilocybin 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. Aim: Evaluate changes in resting-state functional connectivity (RSFC) at 1 week and 3 months after one psilocybin dose in 10 healthy psychedelic-naïve volunteers and explore associations between change in RSFC and related measures. Methods: Participants received 0.2–0.3 mg/kg psilocybin in a controlled setting. Participants completed resting-state functional magnetic resonance imaging (fMRI) scans at baseline, 1-week and 3-month post-administration and [11C]Cimbi-36 PET scans at baseline and 1 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. Results: Psilocybin was well tolerated and produced positive changes in well-being. At 1 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 1 week or 3 months, nor changes in region-to-region RSFC. Exploratory analyses indicated that decreased ECN RSFC at 1 week predicted increased mindfulness at 3 months ( r = −0.65). Conclusions: These 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 3 months, when personality changes are observed, remain to be identified.

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Functional Alterations in Cerebellar Functional Connectivity in Anxiety Disorders

The Cerebellum ◽

10.1007/s12311-020-01213-8 ◽

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.

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Impact of Binge Drinking During College on Resting State Functional Connectivity

10.1101/2021.02.09.430381 ◽

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.

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Altered hypothalamus functional connectivity with limbic system in fibromyalgia and the modulation effect of intervention

10.21203/rs.2.20627/v1 ◽

2020 ◽

Author(s):

Jian Kong ◽

Yiting Huang ◽

Jiao Liu ◽

Siyi Yu ◽

Ming Cheng ◽

...

Keyword(s):

Functional Connectivity ◽

Limbic System ◽

Resting State ◽

Tai Chi ◽

Effective Connectivity ◽

Resting State Fmri ◽

Trial Registration ◽

Modulation Effect ◽

Resting State Functional Connectivity ◽

Before And After

Abstract Background: This study aims to investigate the resting state functional connectivity (rsFC) changes of the hypothalamus in Fibromyalgia patients and the modulation effect of effective treatments. Methods: Fibromyalgia patients and matched healthy controls (HC’s) were recruited. Resting state fMRI data were collected from fibromyalgia patients before and after a 12-week Tai Chi intervention and once from HC’s. Results: Data analysis showed that fibromyalgia patients displayed significantly decreased medial hypothalamus (MH) rsFC with the thalamus and amygdala when compared to HC’s at baseline. After the intervention, fibromyalgia patients showed increased (normalized) MH rsFC in the thalamus and amygdala. Effective connectivity analysis showed disrupted MH and thalamus interaction in fibromyalgia, which nonetheless could be partially restored by Tai Chi. Conclusions: Elucidating the role of the diencephalon and limbic system in the pathophysiology and development of fibromyalgia may facilitate the development of new treatment methods for this prevalent disorder. Trial registration: Trial registration ClinicalTrials.gov Identifier: NCT02407665. Registered 3 April 2015 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02407665

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

Translational Psychiatry ◽

10.1038/s41398-020-01101-z ◽

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.

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The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults

Alzheimer s Research & Therapy ◽

10.1186/s13195-019-0573-1 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Chemin Lin ◽

Maria Ly ◽

Helmet T. Karim ◽

Wenjing Wei ◽

Beth E. Snitz ◽

...

Keyword(s):

Neural Networks ◽

Older Adults ◽

Cognitive Function ◽

Functional Connectivity ◽

Resting State ◽

Clinical Symptoms ◽

Rate Of Change ◽

Resting State Functional Connectivity ◽

Cognitive Changes ◽

Cognitively Normal

Abstract Background Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. Methods We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. Results Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. Conclusions Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.

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Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients

European Psychiatry ◽

10.1016/j.eurpsy.2015.12.005 ◽

2016 ◽

Vol 34 ◽

pp. 56-63 ◽

Cited By ~ 28

Author(s):

G. Rey ◽

C Piguet ◽

A Benders ◽

S Favre ◽

SB Eickhoff ◽

...

Keyword(s):

Bipolar Disorder ◽

Functional Connectivity ◽

Resting State ◽

Clinical Symptoms ◽

Mood State ◽

A Priori ◽

Emotion Processing ◽

Population Sample ◽

Small Population ◽

Resting State Functional Connectivity

AbstractBackgroundPrevious functional magnetic resonance imaging studies in bipolar disorder (BD) have evidenced changes in functional connectivity (FC) in brain areas associated with emotion processing, but how these changes vary with mood state and specific clinical symptoms is not fully understood.MethodsWe investigated resting-state FC between a priori regions of interest (ROIs) from the default-mode network and key structures for emotion processing and regulation in 27 BD patients and 27 matched healthy controls. We further compared connectivity patterns in subgroups of 15 euthymic and 12 non-euthymic patients and tested for correlations of the connectivity strength with measures of mood, anxiety, and rumination tendency. No correction for multiple comparisons was applied given the small population sample and pre-defined target ROIs.ResultsOverall, regardless of mood state, BD patients exhibited increased FC of the left amygdala with left sgACC and PCC, relative to controls. In addition, non-euthymic BD patients showed distinctive decrease in FC between right amygdala and sgACC, whereas euthymic patients showed lower FC between PCC and sgACC. Euthymic patients also displayed increased FC between sgACC and right VLPFC. The sgACC–PCC and sgACC–left amygdala connections were modulated by rumination tendency in non-euthymic patients, whereas the sgACC-VLPFC connection was modulated by both the current mood and tendency to ruminate.ConclusionsOur results suggest that sgACC-amygdala coupling is critically affected during mood episodes, and that FC of sgACC play a pivotal role in mood normalization through its interactions with the VLPFC and PCC. However, these preliminary findings require replication with larger samples of patients.

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Finger Tapping Task Activation vs. TMS Hotspot: Different Locations and Networks

Brain Topography ◽

10.1007/s10548-019-00741-9 ◽

2019 ◽

Vol 33 (1) ◽

pp. 123-134 ◽

Cited By ~ 2

Author(s):

Jue Wang ◽

Hai-Jiang Meng ◽

Gong-Jun Ji ◽

Ying Jing ◽

Hong-Xiao Wang ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Resting State Fmri ◽

Finger Tapping ◽

Functional Magnetic Resonance ◽

Resting State Functional Connectivity ◽

Significant Difference ◽

Human Motor ◽

Healthy Participants ◽

Task Activation

Abstract Both functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have been used to non-invasively localize the human motor functional area. These locations can be clinically used as stimulation target of TMS treatment. However, it has been reported that the finger tapping fMRI activation and TMS hotspot were not well-overlapped. The aim of the current study was to measure the distance between the finger tapping fMRI activation and the TMS hotspot, and more importantly, to compare the network difference by using resting-state fMRI. Thirty healthy participants underwent resting-state fMRI, task fMRI, and then TMS hotspot localization. We found significant difference of locations between finger tapping fMRI activation and TMS hotspot. Specifically, the finger tapping fMRI activation was more lateral than the TMS hotspot in the premotor area. The fMRI activation peak and TMS hotspot were taken as seeds for resting-state functional connectivity analyses. Compared with TMS hotspot, finger tapping fMRI activation peak showed more intensive functional connectivity with, e.g., the bilateral premotor, insula, putamen, and right globus pallidus. The findings more intensive networks of finger tapping activation than TMS hotspot suggest that TMS treatment targeting on the fMRI activation area might result in more remote effects and would be more helpful for TMS treatment on movement disorders.

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Prevalent and sex-biased breathing patterns modify functional connectivity MRI in young adults

Nature Communications ◽

10.1038/s41467-020-18974-9 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Charles J. Lynch ◽

Benjamin M. Silver ◽

Marc J. Dubin ◽

Alex Martin ◽

Henning U. Voss ◽

...

Keyword(s):

Young Adults ◽

Functional Connectivity ◽

Resting State ◽

Resting State Fmri ◽

Resonance Imaging ◽

Breathing Patterns ◽

Resting State Functional Connectivity ◽

Brain Organization ◽

Normal Breathing ◽

Functional Connectivity Mri

Abstract Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex. Deep breaths are not sex-biased. Bursts, which are serial taperings of respiratory depth typically spanning minutes at a time, are more common in males. Bursts share features of chemoreflex-driven clinical breathing patterns that also occur primarily in males, with notable neurological, psychiatric, medical, and lifespan associations. These results identify common breathing patterns in healthy young adults with distinct influences on functional connectivity and an ability to differentially influence resting state fMRI studies.

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