Deficits in working memory (WM) are a hallmark of neuropsy-chiatric disorders such as schizophrenia, yet their neurobiological basis remains poorly understood. Glutamate N-methyl-D-aspartate receptors (NMDARs) are critical for spatial WM (sWM), with NMDAR antagonist ketamine known to attenuate task-evoked activation and reduce sWM accuracy. Cortical microcircuit models hypothesize that NMDAR...
Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition....
Precision psychiatry aims to identify markers of interindividual variability that allow for predicting the right treatment for each patient. However, bridging the gap between molecular-level manipulations and neural systems-level functional alterations remains an unsolved problem in psychiatry. After decades of low success rates in pharmaceutical research and development for psychiatric drugs,...
Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to...
This report introduces the activities of eight one-week workshops that were held during the summer of 2017 on the topic “Technology and Consciousness.” Participants in the series of workshops approached the subject from many different perspectives, with the overall goal of exploring the possibility of machine consciousness, and assessing its potential implications. The body of this initial...
BackgroundThe use of psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.MethodsWe conducted a double-blind, randomized, counterbalanced, crossover study comprising 23 healthy human participants who received placebo and...
Background: Lysergic acid diethylamide (LSD) has agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, specific receptor contributions to its neurobiological effects remain unknown. Methods: We therefore conducted a double-blind, randomized, counterbalanced, cross-over studyduring which 24 healthy human participants received...
Neuropsychiatric diseases such as schizophrenia and bipolar illness alter the structure and function of distributed neural networks. Functional neuroimaging tools have evolved sufficiently to reliably detect system-level disturbances in neural networks. This review focuses on recent findings in schizophrenia and bipolar illness using resting-state neuroimaging, an advantageous approach for...
Excitation-inhibition balance (E/I balance) is a fundamental property of cortical microcircuitry. Disruption of E/I balance in prefrontal cortex is hypothesized to underlie cognitive deficits observed in neuropsychiatric illnesses such as schizophrenia. To elucidate the link between these phenomena, we incorporated synaptic disinhibition, via N-methyl-D-aspartate receptor perturbation on...
Glutamatergic neurotransmission mediated by N-methyl-d-aspartate (NMDA) receptors is vital for the cortical computations underlying cognition and might be disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale brain systems with multiple interacting regions. A prominent...