Studies of perception and cognition in schizophrenia (SCZ) show neuronal background noise (ongoing activity) to intermittently overwhelm the processing of external stimuli. This increased noise, relative to the activity evoked by the stimulus, results in temporal imprecision and higher variability of behavioral responses. What, however, are the neural correlates of temporal imprecision in SCZ behavior? We first report a decrease in electroencephalography signal-to-noise ratio (SNR) in two SCZ datasets and tasks in the broadband (1–80 Hz), theta (4–8 Hz), and alpha (8–13 Hz) bands. SCZ participants also show lower inter-trial phase coherence (ITPC)—consistency over trials in the phase of the signal—in theta. From these ITPC results, we varied phase offsets in a computational simulation, which illustrated phase-based temporal desynchronization. This modeling also provided a necessary link to our results and showed decreased neural synchrony in SCZ in both datasets and tasks when compared with healthy controls. Finally, we showed that reduced SNR and ITPC are related and showed a relationship to temporal precision on the behavioral level, namely reaction times. In conclusion, we demonstrate how temporal imprecision in SCZ neural activity—reduced relative signal strength and phase coherence—mediates temporal imprecision on the behavioral level.

There is a growing resurgence in the study of psychedelic medicines for the treatment of mental health and substance use disorders. However, certain early investigations are marred by questionable research methods, abuses against research participants, and covert Central Intelligence Agency financial involvement. The purpose of this study was to understand how and to what extent people of colour and other vulnerable populations, specifically, individuals who were incarcerated or incapacitated due to mental health issues (inpatients with psychotic disorders), were exploited during the first wave of psychedelic research in the USA (1950–1980). To do so, we reviewed available empirical publications according to current ethical standards. Variables of interest included race and ethnicity of participants, population vulnerability, drug administration conditions, informed consent and undue influence. Our findings draw attention to the history of research abuses against people of colour in Western psychedelic research. In light of these findings, we urge a call-to-action to current psychedelic researchers to prioritise culturally inclusive and socially responsible research methods in current and future studies.

Traditional antidepressants, which act on the serotonin, dopamine, and norepinephrine systems, require many weeks to produce a therapeutic effect and are not effective for every patient. A sub-anesthetic dose of the anesthetic agent ketamine, a glutamate N-methyl-Daspartate receptor antagonist, has been shown to produce a rapid and robust antidepressant effect in treatment-resistant major depressive disorder (MDD). As depressive symptoms typically return after one week following a single infusion, recent work has begun to focus on methods for prolonging the effects. Repeated infusions on a specific dosing schedule are being explored, however, the early identification of treatment responders and non-responders would be beneficial for optimized treatment selection within this population.The mechanisms underlying ketamine's rapid effects conceivably involve the regulation of altered glutamatergic signaling in MDD, though this is not yet completely understood.Understanding of the central mechanisms mediating ketamine's rapid antidepressant effects may be increased through the use of non-invasive electroencephalographic measures, including resting electroencephalography (EEG) and the mismatch negativity (MMN) event-related potential. These measures have been shown to be altered in depressed individuals and are sensitive to ketamine administration.The primary objectives of this study were to 1) examine acute changes in EEG-and MMN-derived indices, immediately post-and two hours postinfusion, with a sub-anesthetic ketamine dose in comparison to an active placebo (midazolam), and 2) to examine their relationships with early and sustained antidepressant treatment response to ketamine within an eight week clinical trial involving three study phases. IIIKetamine decreased measures of scalp-level alpha and theta resting activity, immediately postinfusion, and increased gamma immediately and two hours postinfusion. An increase in source-localized anterior cingulate activity two hours postinfusion was also observed. Regarding the MMN, ketamine reduced frontal amplitudes as well as theta event-related oscillations and source-localized peak frontal generator activity. Measures of resting theta and change in gamma, as well as left frontal MMN amplitude, theta event-related oscillations, baseline left phase locking factor, and baseline right inferior temporal lobe activity were predictive of decreases in depressive symptoms at both early and sustained treatment time points. Alpha power was predictive of decrease in suicidal ideation, though the relationship with baseline and early change in symptoms was stronger.These findings contribute to our understanding of the role of baseline and ketamineinduced changes in both resting and task-evoked electrophysiological measures, and may have the potential to act as non-invasive biomarkers of antidepressant response prediction to glutamatergic agents. IV PREFACEThis thesis is comprised of manuscripts (Chapters 2-3) which are in preparation for submission for publication in peer-reviewed jo...

Experiences of past and present oppression/discrimination towards Turtle Island's Indigenous peoples are pervasive, contributing to symptoms of stress and trauma. Psychedelic substances have been shown to be effective for treating multiple disorders; however, there is a lack of research within Indigenous groups. This study examined the effects of naturalistic psychedelic use on recalled psychological distress and trauma symptoms among Indigenous peoples living in the United States and Canada who had experienced racial trauma. Participants were asked to recall a memorable psychedelic experience and report experiences of past racial trauma and retrospective changes in mental health symptoms within a cross-sectional internet-based survey focusing on people of colour in North America. Sixty-six participants (74.3% residents of Canada, 60.6% female, mean age of 35.9 years) self-identified as Indigenous. Participants mostly reported oral intake of psilocybin, 3,4-methylenedioxymethamphetamine, or lysergic acid diethylamide, and reported frequent experiences of ethnic discrimination and high levels of related stress. Participants recalled experiencing fewer symptoms of depression, anxiety, stress, trauma, symptoms of discrimination, and alcohol use in the 30 days after (vs. before) the psychedelic experience. Greater overall changes were recalled following psilocybin consumption, whereas differential effects were found based on Tribal land, reservation, or reserve residency and participant sex. Exploratory analyses suggested that measures of ethnic discrimination, residency, substance consumed, and sex were related to recalled changes in symptoms. As the healing powers of psychedelic medicines gain in mainstream popularity, one must consider the historical contexts, implications, and perspectives of Indigenous peoples. Several reflection questions are recommended to aid psychedelic stakeholders in conducting their work in an allied manner. Public Significance StatementThe present study found that naturalistic psychedelic substance consumption led to recalled improvements in symptoms of depression, anxiety, stress, trauma symptoms of discrimination, and alcohol use, in the 30 days after (vs. before) the psychedelic experience in Indigenous people who had experienced racial trauma. In particular, psilocybin led to the greatest recalled improvements, whereas differential