Altered states of consciousness (ASCs) provide models through which the necessary and sufficient neural underpinnings for consciousness can be characterised. Indeed, the study of ASCs through human functional neuroimaging has identified large-scale cortical networks (such as the default mode network; DMN) whose disintegration is common across both pharmacological transient and pathological chronic ASCs. However, these cortico-centric network accounts have largely been unable to fully characterise fundamental neurobiological processes which may underpin disruptions of consciousness and/or network changes. Instead, such work has mainly been performed in preclinical animal experiments and in lesion studies, which have identified that brainstem neurotransmitter nuclei – among them in particular the monoaminergic source nuclei and transmitter systems – are consistently implicated in both pharmacological and pathological perturbations of wakefulness/consciousness. Thus, the dysfunction of these nuclei could underpin human ASCs and network changes, and their assessment might correspondingly hold translational, diagnostic and therapy-informing utility. To address this central question, in this thesis I used resting state fMRI recordings to analyse how the dopaminergic ventral tegmental area (VTA) and the serotonergic raphe nuclei are affected in pharmacological (propofol sedation, lysergic acid diethylamide & psilocybin administration) and pathological (disorders of consciousness, DOC) contexts, and how these findings relate to network-level impairments, as well as previous animal findings concerning the same nuclei. In Chapter II, I assessed how functional connectivity of the VTA is altered across both propofol sedation and DOC patients. I found that in both sedation and DOC, VTA connectivity is disrupted from the main node of the DMN in the precuneus/posterior cingulate cortex, revealing a connectivity impairment universal to both ASCs. The extent of this VTA connectivity impairment was associated with DMN disconnectivity, as well as behaviour and/or outcome measures. Furthermore, I found that this connectivity could be upregulated by a dopaminergic agonist. Chapter III further developed the findings of the previous chapter by aiming to integrate these with a pre-existing DOC disease framework called the anterior forebrain mesocircuit, which regards thalamic impairment as central to DOC pathoyphysiology. I found that VTA-thalamus connectivity is also impaired in DOC patients, but that this was undetectable in seed-to-voxel contrasts due to a sub-group of patients showing control-like connectivity levels. Patients who showed such preserved VTA-thalamus connectivity also were found to be responsive in an fMRI volitional task (Tennis task), and the greater this VTA-thalamus connectivity strength was, the less impairment of whole brain complexity of the fMRI signal was observed, which supports the concept that thalamic and mesocircuit impairment in DOC might be at least partially mediated through dopaminergic dysfunction. Chapter IV focussed on psychedelic ASCs, which are elicited by serotonergic psychedelic drugs, such as lysergic acid diethylamide (LSD). I found that serotonergic raphe nuclei connectivity is powerfully disrupted in acute LSD administrations – strikingly once more to the posterior DMN node in the precuneus/posterior cingulate. The extent of this disruption was again associated with DMN disintegration, and showed causal mediation effects on hallmarks of the psychedelic experience. I also demonstrated that the cortical ratio of 5HT2A receptors over 5HT1A receptors might be driving this raphe uncoupling effect. Based on these results and pre-existing literature, I hypothesised that this observed connectivity disruption in acute psychedelic administration may have adaptive sub-/post-acute effects on raphe functionality that might underpin psychedelic therapeutic effects, e.g. in depression. Chapter V tested said hypothesis of psychedelic-induced sub-/post-acute raphe changes in two depression cohorts who received psilocybin. In data-driven analyses, I found that only post-acute connectivity of the raphe to the precuneus was associated with strength of depression symptom reduction across both trials. Psychedelic treatment induced significant sub- and post-acute upregulations of raphe-precuneus coupling, whereas SSRI treatment did not. Additionally, raphe-precuneus connectivity enhancements also positively covaried with DMN integrity and were accompanied by increases in spontaneous raphe BOLD activity. This provides preliminary evidence that a post-acute upregulation of raphe functionality might underpin psychedelic anti-depressant effects. Altogether, these studies demonstrate that monoaminergic nuclei dysfunction might be a hallmark common to various different ASCs – and that functionality of these brainstem sources of non-classical transmitters might plausibly be associated with behavioural, clinical and network-level phenomena associated with perturbed consciousness. This provides various necessary translational bridges between preclinical and clinical work, and hints at the possibility of non-invasive neurotransmitter systems-level assessments with diagnostic and therapeutic utility.