Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis

The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral ‘limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal ‘associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness

Body integrity identity disorder: deranged body processing, right fronto-parietal dysfunction, and phenomenological experience of body incongruity

Body integrity identity disorder (BIID) is characterised by profound experience of incongruity between the biological and desired body structure. The condition manifests in "non-belonging" of body parts, and the subsequent desire to amputate, paralyse or disable a limb. Little is known about BIID; however, a neuropsychological model implicating right fronto-parietal and insular networks is emerging, with potential disruption to body representation. We argue that, as there is scant systematic research on BIID published to date and much of the research is methodologically weak, it is premature to assume that the only process underlying bodily experience that is compromised is body representation. The present review systematically investigates which aspects of neurological processing of the body, and sense of self, may be compromised in BIID. We argue that the disorder most likely reflects dysregulation in multiple levels of body processing. That is, the disunity between self and the body could arguably come about through congenital and/or developmental disruption of body representations, which, together with altered multisensory integration, may preclude the experience of self-attribution and embodiment of affected body parts. Ulimately, there is a need for official diagnostic criteria to facilitate epidemiological characterisation of BIID, and for further research to systematically investigate which aspects of body representation and processing are truly compromised in the disorder