Effective connectivity changes in LSD-induced altered states of consciousness in humans

Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico–striato–thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.

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Impaired consciousness is linked to changes in effective connectivity of the posterior cingulate cortex within the default mode network

NeuroImage ◽

10.1016/j.neuroimage.2015.01.037 ◽

2015 ◽

Vol 110 ◽

pp. 101-109 ◽

Cited By ~ 57

Author(s):

Julia Sophia Crone ◽

Matthias Schurz ◽

Yvonne Höller ◽

Jürgen Bergmann ◽

Martin Monti ◽

...

Keyword(s):

Default Mode Network ◽

Effective Connectivity ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Impaired Consciousness ◽

Default Mode ◽

Posterior Cingulate

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Altered trkB neurotrophin receptor activation does not influence the N-methyl-d-aspartate receptor antagonist-mediated neurotoxicity in mouse posterior cingulate cortex

Neuroscience Letters ◽

10.1016/s0304-3940(03)00744-4 ◽

2003 ◽

Vol 350 (1) ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Jussi Väisänen ◽

Tommi Saarelainen ◽

Eija Koponen ◽

Eero Castrén

Keyword(s):

Receptor Antagonist ◽

Cingulate Cortex ◽

Receptor Activation ◽

Posterior Cingulate Cortex ◽

Neurotrophin Receptor ◽

Posterior Cingulate ◽

Aspartate Receptor

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M142. INCREASED VENTRAL STRIATAL FUNCTIONAL CONNECTIVITY IN PATIENTS WITH SCHIZOPHRENIA DURING REWARD ANTICIPATION

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.454 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S189-S190

Author(s):

Fabien Carruzzo ◽

Matthias Kirschner ◽

Stefan Kaiser

Keyword(s):

Functional Connectivity ◽

Parietal Cortex ◽

Negative Symptoms ◽

Ventral Striatum ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Healthy Controls ◽

Posterior Cingulate ◽

Reward Anticipation ◽

The Right

Abstract Background Recent studies have pointed at the ventral striatum as one of the main candidates underlying motivational dysfunctions in schizophrenia. Patients with negative symptoms show decreased BOLD activity in the ventral striatum and this activity strongly correlates with apathy scores during reward anticipation. While in patients with schizophrenia blunted ventral striatal activation during reward anticipation has been widely reported, little is known about abnormal striatal functional connectivity during reward anticipation. In this study, we performed generalized whole-brain psychophysiological interaction (gPPI) analyses using the right and left ventral striatum as seeds in schizophrenia patients with apathy and reduced ventral striatal activation from two published fMRI studies (Kirschner et al., 2016; Stepien et al., 2018). Methods Forty-four healthy controls (18 females, mean age = 31.1) and 40 patients with schizophrenia (10 females, mean age = 32.5) performed a variant of the Monetary Incentive Delay task within an fMRI design. Negative symptoms were assessed with the Brief Negative Symptoms Scale (BNSS). GPPI analyses were done using the PPPI toolbox on SPM 8. To examine potential difference in striatal functional connectivity, we performed two sample t-tests between patients with schizophrenia and healthy controls using the contrast [High Reward Anticipation – No Reward Anticipation]. Results Patients with schizophrenia showed increased functional connectivity between the right ventral striatum and the anterior cingulate cortex, posterior cingulate cortex, cerebellum, motor cortex, parietal cortex, temporo-parietal junction and thalamus compared to controls (cluster-level FDR p<0.05). No higher connectivity was found in controls compared to patients. For the regions with increased functional connectivity, we performed correlations between the patients’ gPPI signal and apathy. We found significant correlations between apathy and functional connectivity between the right ventral striatum and the right posterior cingulate cortex (r=0.40, p<.05) and right parietal cortex (r=0.39, p<.05). Discussion Our preliminary results indicate that physiological changes in the ventral striatum lead to dysfunctional connectivity with a cortex-wide network, affecting both cortico-striatal-thalamic-cortical and cortico-striatal-thalamic-cerebellar pathways. In addition, we show that some of these changes are related to apathy levels. This work provides novel insights in cortico-striatal network dysfunction during reward processing in patients with schizophrenia.

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Beyond the disconnectivity hypothesis of schizophrenia

Cerebral Cortex ◽

10.1093/cercor/bhz161 ◽

2019 ◽

Vol 30 (3) ◽

pp. 1213-1233 ◽

Cited By ~ 3

Author(s):

Edmund T Rolls ◽

Wei Cheng ◽

Matthieu Gilson ◽

Weikang Gong ◽

Gustavo Deco ◽

...

Keyword(s):

Mechanistic Model ◽

Effective Connectivity ◽

Cingulate Cortex ◽

Brain Regions ◽

Posterior Cingulate Cortex ◽

Parahippocampal Gyrus ◽

Positive Symptoms ◽

Posterior Cingulate ◽

Variance Parameter

Abstract To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model. Effective connectivity (EC) was measured in 180 participants with schizophrenia and 208 controls. For the significantly different effective connectivities in schizophrenia, on average the forward (stronger) effective connectivities were smaller, whereas the backward connectivities tended to be larger. Further, higher EC in schizophrenia was found from the precuneus and posterior cingulate cortex (PCC) to areas such as the parahippocampal, hippocampal, temporal, fusiform, and occipital cortices. These are backward effective connectivities and were positively correlated with the positive symptoms of schizophrenia. Lower effective connectivities were found from temporal and other regions and were negatively correlated with the symptoms, especially the negative and general symptoms. Further, a signal variance parameter was increased for areas that included the parahippocampal gyrus and hippocampus, consistent with the hypothesis that hippocampal overactivity is involved in schizophrenia. This investigation goes beyond the disconnectivity hypothesis by drawing attention to differences in schizophrenia between backprojections and forward connections, with the backward connections from the precuneus and PCC implicated in memory stronger in schizophrenia.

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Altered effective connectivity anchored in the posterior cingulate cortex and the medial prefrontal cortex in cognitively intact elderly APOE ε4 carriers: a preliminary study

Brain Imaging and Behavior ◽

10.1007/s11682-018-9857-5 ◽

2018 ◽

Vol 13 (1) ◽

pp. 270-282 ◽

Cited By ~ 8

Author(s):

Xiao Luo ◽

◽

Kaicheng Li ◽

Y. L. Jia ◽

Qingze Zeng ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Effective Connectivity ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Posterior Cingulate ◽

Apoe Ε4 ◽

Preliminary Study ◽

Cognitively Intact

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Are inhibitory and excitatory neurotransmitter levels in the posterior cingulate cortex associated with MS fatigue?

10.26226/morressier.59a3e8b4d462b8028d89445c ◽

2017 ◽

Author(s):

Karen A. Ribbons

Keyword(s):

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Excitatory Neurotransmitter ◽

Posterior Cingulate

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Serum Vitamin D and Cingulate Cortex Thickness in Older Adults: Quantitative MRI of the Brain

Current Alzheimer Research ◽

10.2174/1567205016666191113124356 ◽

2019 ◽

Vol 16 (11) ◽

pp. 1063-1071 ◽

Cited By ~ 1

Author(s):

Gonzague Foucault ◽

Guillaume T Duval ◽

Romain Simon ◽

Olivier Beauchet ◽

Mickael Dinomais ◽

...

Keyword(s):

Older Adults ◽

Vitamin D ◽

Brain Mri ◽

Serum Vitamin ◽

Cingulate Cortex ◽

Posterior Cingulate Cortex ◽

Vitamin D Insufficiency ◽

Anterior Cingulate ◽

Posterior Cingulate ◽

Significant Difference

Background: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults. Method: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables. Results: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (β=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021). Conclusion: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

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