TABLE 2.
Summary of main findings of (pharmacological) manipulation of 5HT and Ach.
| Study | Modality(species) | Analysismethod | Manipulation | Main effects of manipulation on intrinsic correlations |
| Tanabe et al., 2011 | fMRI (humans) | ICA-based back-reconstruction | Nicotine (nACh receptor agonist) | Reduced correlations within the DMN. Increased correlations within extrastriate cortex. |
| McCabe and Mishor, 2011 | fMRI (humans) | Seed-based correlation | Citalopram (SSRI) | Citalopram: reduced amygdala-vmPFC correlation. |
| McCabe et al., 2011 | fMRI (humans) | Seed-based correlation | Citalopram (SSRI) | Reduced correlation between left dmPFC and left hippocampus. |
| van de Ven et al., 2013 | fMRI (humans) | Dual regression | Escitalopram (SSRI) | Reduced DMN correlations with PCC, ACC, hippocampus, and lateral parietal cortex. |
| Schaefer et al., 2014 | fMRI (humans) | Graph theoretic analysis (FCD) | Escitalopram (SSRI) | Reduced global strength of correlation. Local increases in thalamus and cerebellum. |
| Klaassens et al., 2015 | fMRI (humans) | Dual regression | Sertraline (SSRI) | Widespread decreases in correlation with DMN; executive control; visual and sensorimotor networks. Increased correlation between auditory network and PCC/precuneus. |
| Carhart-Harris et al., 2016 | fMRI (humans) | Seed-based correlation | LSD (5HT agonist) | Increase in correlation between visual cortex and widespread regions of the cortex and between the parahippocampal cortex and the retrosplenial cortex and PCC, and increased correlations between parahippocampal cortex and dorsal mPFC and right dorsolateral PFC. |
| Tagliazucchi et al., 2016 | fMRI (humans) | Graph theoretic analysis. Seed-based correlation | LSD (5HT agonist) | Increased global correlation strength. Brain regions that showed altered correlation strength overlapped with 5HT2A-r distributions. Increased correlation between four seeds (PFC, parietal cortex, precuneus, and thalamus) and sensorimotor areas. Reduced modularity. Increased participation coefficient of frontal and midline regions. Reduced rich-club coefficient. |
| Klaassens et al., 2017 | fMRI (humans) | Dual regression | Citalopram (SSRI) Galantamine (nACh receptor agonist) | Citalopram: reduction of correlations within the sensorimotor network, PFN, DMN, and executive control network. Galantamine: increased correlations between polar occipital network and distributed regions; between an auditory network and regions of the DMN and somatosensory cortex; reduced correlations within the DMN, and between DMN and lateral and inferior occipital cortices; between the FPN and DMN, inferior temporal and cerebellar regions. |
| Deco et al., 2018 | fMRI (humans) | Dynamic FC + computational model | LSD (5HT agonist) | The model captured the effect of 5HT2A-r stimulation as an increase in gain to explain the effect of LSD on the distribution of FC dynamics. |
| Turchi et al., 2018 | fMRI (rhesus macaque) | Global signal correlation and dual regression | Pharmacological inactivation of basal forebrain | Broad reductions in coupling of local activity with the global signal, corresponding spatially to the inactivated location. Topography of individual RSNs unaffected. |
| Lord et al., 2018 | fMRI (humans) | Dynamic FC | Psilocybin (5HT agonist) | Longer dwell times for a global FC component. Reduced dwell times for FPN. |
| Preller et al., 2018 | fMRI (humans) | Graph theoretic analysis (FCD) Seed-based correlation | LSD (5HT agonist) | Reduced correlation (from positive toward zero) in associative networks. Increased correlation (from negative toward zero) in sensorimotor and thalamic networks. LSD effects correlated with 5HT2A-r distributions. Reduced correlation between sensorimotor areas and global signal. |
| Pfeffer et al., 2018 | MEG (humans) | DFA + computational model | Donepezil (acetylcholinesterase inhibitor) | No effect of donepezil. |
| Pfeffer et al., 2019 | MEG (humans) | Graph theoretic analysis + computational model | Donepezil (acetylcholinesterase inhibitor) | Rest: reduced correlation strength. Computational models indicate that effect can be accounted for by an increase in gain. |
| Grandjean et al., 2019 | fMRI, MUA, and LFP (mice) | GLM analysis | Blockwise optogenetic stimulation of DR | Wide suppression of cortical CBV response. Suppression of cortical MUA, and δ LFP power, which spatially correlated with the cortical CBV response. CBV response correlated with distribution of 5HT 1F, 2A, 2C receptors, but not 1A and 1B receptors. Correlations with receptor maps were stronger than correlation with DR projection profile. |
5HT: serotonin; ACh: acetylcholine; ACC: anterior cingulate cortex; CBV: cerebral blood volume; DMN: default mode network; dmPFC: dorsomedial prefrontal cortex; DR: dorsal raphe; FC: functional connectivity; FPN: frontoparietal network; FCD: Functional connectivity density; PCC: posterior cingulate cortex; nACh: nicotinic acetylcholine; PCA: principle component analysis; SSRI: selective serotonin reuptake inhibitor.