Psilocybin with psychological support is showing promise as a treatment model in psychiatry but its therapeutic mechanisms are poorly understood. Here, cerebral blood flow (CBF) and blood oxygen-level dependent (BOLD) resting-state functional connectivity (RSFC) were measured with functional magnetic resonance imaging (fMRI) before and after treatment with psilocybin (serotonin agonist) for treatment-resistant depression (TRD). Quality pre and post treatment fMRI data were collected from 16 of 19 patients. Decreased depressive symptoms were observed in all 19 patients at 1-week post-treatment and 47% met criteria for response at 5 weeks. Whole-brain analyses revealed post-treatment decreases in CBF in the temporal cortex, including the amygdala. Decreased amygdala CBF correlated with reduced depressive symptoms. Focusing on a priori selected circuitry for RSFC analyses, increased RSFC was observed within the default-mode network (DMN) post-treatment. Increased ventromedial prefrontal cortex-bilateral inferior lateral parietal cortex RSFC was predictive of treatment response at 5-weeks, as was decreased parahippocampal-prefrontal cortex RSFC. These data fill an important knowledge gap regarding the post-treatment brain effects of psilocybin, and are the first in depressed patients. The post-treatment brain changes are different to previously observed acute effects of psilocybin and other ‘psychedelics’ yet were related to clinical outcomes. A ‘reset’ therapeutic mechanism is proposed.

The macaque V5/MT complex comprises several sub-regions but little is known of their human homologues. We examined human V5/MT with fMRI in terms of specificity to optic flow stimuli, a key characteristic of macaque MST. Stimuli were large fields of moving dots, forming coherent global flow patterns. Random motion was used as a control. Retinotopic mapping was also conducted. The previously suggested existence of at least two distinct sub-regions, MT and MST, within the V5/MT complex was confirmed. Human MT is activated about equally by all moving dot patterns, including random motion, suggesting that it has little sensitivity to global flow structure. As previously described, this region shows strong signs of retinotopic organization and is only weakly activated by stimuli confined to the ipsilateral hemifield. In human MST, located immediately anterior to MT and strongly driven by ipsilateral stimuli, activation varies markedly with optic flow structure. The strongest activation is produced by complex flow that contains multiple flow components (expansion, contraction and rotation). Single components produce rather less response, while rigid translation and random motion produce less still. The results suggest that human MST is strongly specialized for encoding global flow properties, while human MT is less so.

An essential function of visual processing is to establish the position of the body in space and, in concert with the other sense systems, to monitor movement of the whole body, or "egomotion." A key cue to egomotion is optic flow. For example, forward motion through the environment generates an expanding pattern of flow on the retina, and (with eyes fixed centrally) the direction of heading corresponds to the center of expansion [1]. In macaques, visual cortical area MST is sensitive to optic-flow structure [2, 3], and it has been suggested that MST has a central role in the computation of heading [4]. However, here we identify two areas of the human brain that represent visual cues to egomotion more directly than does MST. These areas respond strongly to a single optic-flow stimulus but become relatively unresponsive when the stimulus is surrounded with further flow patches and thereby made inconsistent with egomotion. One is putative area VIP in the anterior portion of the intraparietal sulcus. The other is a new visual area, which we refer to as cingulate sulcus visual area (CSv). Areas V1-V4 and MT respond about equally to both types of flow stimulus. MST has intermediate properties, responding well to multiple patches but with a modest preference for a single, egomotion-compatible patch. We suggest that MST is merely an intermediate processing stage for visual cues to egomotion and that such cues are more comprehensively encoded by VIP and CSv.